Ts the authors' views.Authors' contributionsAT implemented the software and carriedTs the authors' views.Authors' contributionsAT implemented

Ts the authors’ views.Authors’ contributionsAT implemented the software and carried
Ts the authors’ views.Authors’ contributionsAT implemented the software and carried out the experiments. All authors participated in developing the algo-Page 12 of(page number not for citation purposes)BMC Bioinformatics 2008, 9:http://www.biomedcentral.com/1471-2105/9/
Ingley Cell Communication and Signaling 2012, 10:21 http://www.biosignaling.com/content/10/1/REVIEWOpen AccessFunctions of the Lyn tyrosine kinase in health and diseaseEvan Ingley*Abstract: Src Lasalocid (sodium) side effects family kinases such as Lyn are important signaling intermediaries, relaying and modulating different inputs to regulate various outputs, such as proliferation, differentiation, apoptosis, migration and metabolism. Intriguingly, Lyn can mediate both positive and negative signaling processes within the same or different cellular contexts. This duality is exemplified by the B-cell defect in Lyn-/- mice in which Lyn is essential for negative regulation of the B-cell receptor; conversely, B-cells expressing a dominant active mutant of Lyn (Lynup/up) have elevated activities of positive regulators of the B-cell receptor due to this hyperactive kinase. Lyn has wellestablished functions in most haematopoietic cells, viz. progenitors via influencing c-kit signaling, through to mature cell receptor/integrin signaling, e.g. erythrocytes, platelets, mast cells and macrophages. Consequently, there is an important role for this kinase in regulating hematopoietic abnormalities. Lyn is an important regulator of autoimmune diseases such as asthma and psoriasis, due to its profound ability to influence immune cell signaling. Lyn has also been found to be important for maintaining the leukemic phenotype of many different liquid cancers including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and B-cell lymphocytic leukaemia (BCLL). Lyn is also expressed in some PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 solid tumors and here too it is establishing itself as a potential therapeutic target for prostate, glioblastoma, colon and more aggressive subtypes of breast cancer. Lay Abstract: To relay information, a cell uses enzymes that put molecular markers on specific proteins so they interact with other proteins or move to specific parts of the cell to have particular functions. A protein called Lyn is one of these enzymes that regulate information transfer within cells to modulate cell growth, survival and movement. Depending on which type of cell and the source of the information input, Lyn can positively or negatively regulate the information output. This ability of Lyn to be able to both turn on and turn off the relay of information inside cells makes it difficult to fully understand its precise function in each specific circumstance. Lyn has important functions for cells involved in blood development, including different while blood cells as well as red blood cells, and in particular for the immune cells that produce antibodies (B-cells), as exemplified by the major B-cell abnormalities that mice with mutations in the Lyn gene display. Certain types of leukaemia and lymphoma appear to have too much Lyn activity that in part causes the characteristics of these diseases, suggesting it may be a good target to develop new anti-leukaemia drugs. Furthermore, some specific types, and even specific subtypes, of solid cancers, e.g. prostate, brain and breast cancer can also have abnormal regulation of Lyn. Consequently, targeting this protein in these cancers could also prove to be beneficial. Keywords: Lyn tyrosine kinase, Src family ki.

S of Enzymatic Analysis. New York: (ed. Bergmeyer HV) Academic Press

S of Enzymatic Analysis. New York: (ed. Bergmeyer HV) Academic Press; 1978:875?79. 25. Tandon SK, Singh S, Prasad S, Khandekar K, Dwivedi VK, Chatterjee M, Mathur N: Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or their combination in rat. Toxicol Lett 2003, 145:211?17. 26. Yoshida S: Re-evaluation of acute neurotoxic effects of Cd2+ on mesencephalic trigeminal neurons of the adult rat. Brain Res 2001, 892:102?10. 27. M dez-Armenta M, R s C: Cadmium neurotoxicity. Environ Toxicol Pharmacol 2007, 23:350?58. 28. Shukla A, Shukla GS, Srimal RC: Cadmium-induced alterations in bloodbrain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat. Hum Exp Toxicol 1996, 15:400?05. 29. Rikans LE, Yamano T: Mechanisms of cadmium-mediated acute hepatotoxicity. J Biochem Mol Toxicol 2000, 14:110?17. 30. Abdalla FH, Schmatz R, Cardoso AM, Carvalho FB, Baldissarelli J, de Oliveira JS, Rosa MM, Gon lves Nunes MA, Rubin MA, da Cruz IB, Barbisan F, Dressler VL, Pereira LB, Schetinger MR, Morsch VM, Gon lves JF, Mazzanti CM: Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na+, K + -ATPase activities. Physiol Behav 2014, 135:152?67. 31. Pari L, Murugavel P, Sitasawad SL, Kumar KS: Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: an in vivo and in vitro study. Life Sci 2007, 80:650?58. 32. Demir HA, Kutluk T, Ceyhan M, Yaci-K eli B, Aky C, Cengiz B, Varan A, Kara A, Yal n B, Se eer G, B pamuk M: Comparison of sulbactam-cefoperazone with carbapenems as empirical monotherapy for febrile neutropenic children with lymphoma and solid tumors. Pediatr Hematol Oncol 2011, 28:299?10. 33. Amara S, Douki T, Garrel C, Favier A, Ben Rhouma K, Sakly M, Abdelmelek H: Effects of static magnetic field and cadmium on oxidative stress andKim et al. BMC Complementary and Alternative Medicine 2014, 14:428 http://www.biomedcentral.com/1472-6882/14/Page 8 of34.35.36.37. 38.39. 40. 41.DNA damage in rat cortex brain and hippocampus. Toxicol Ind Health 2011, 27:99?06. Kanter M, Unsal C, Aktas C, Erboga M: Duvoglustat chemical information Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicol Ind Health doi:10.1177/0748233713504810. Paniagua-Castro N, Escalona-Cardoso G, Madrigal-Bujaidar E, Mart ez-Galero E, Chamorro-Cevallos G: Protection against cadmium-induced teratogenicity in vitro by glycine. Toxicol In Vitro 2008, 22:75?9. Pari L, Murugavel P: Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 2007, 234:44?0. Minami A, Takeda A, Nishibaba D, Takefuta S, Oku N: Cadmium toxicity in synaptic neurotransmission in the brain. Brain Res 2001, 894:336?39. Luchese C, Brand R, de Oliveira R, Nogueira CW, Santos FW: Efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice. Toxicol Lett 2007, 173:181?90. Valko M, Morris H, Cronin MT: Metals, toxicity and oxidative stress. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 Curr Med Chem 2005, 12:1161?208. Quig D: Cysteine metabolism and metal toxicity. Altern Med Rev 1998, 3:262?70. Lu SC: Glutathione synthesis. Biochim Biophys Acta 2013, 1830:3143?153.doi:10.1186/1472-6882-14-428 Cite this article as: Kim et al.: Dendropanax morbifera L eille extract facilitates cadmium BUdR cancer excretion and prevents.S of Enzymatic Analysis. New York: (ed. Bergmeyer HV) Academic Press; 1978:875?79. 25. Tandon SK, Singh S, Prasad S, Khandekar K, Dwivedi VK, Chatterjee M, Mathur N: Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or their combination in rat. Toxicol Lett 2003, 145:211?17. 26. Yoshida S: Re-evaluation of acute neurotoxic effects of Cd2+ on mesencephalic trigeminal neurons of the adult rat. Brain Res 2001, 892:102?10. 27. M dez-Armenta M, R s C: Cadmium neurotoxicity. Environ Toxicol Pharmacol 2007, 23:350?58. 28. Shukla A, Shukla GS, Srimal RC: Cadmium-induced alterations in bloodbrain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat. Hum Exp Toxicol 1996, 15:400?05. 29. Rikans LE, Yamano T: Mechanisms of cadmium-mediated acute hepatotoxicity. J Biochem Mol Toxicol 2000, 14:110?17. 30. Abdalla FH, Schmatz R, Cardoso AM, Carvalho FB, Baldissarelli J, de Oliveira JS, Rosa MM, Gon lves Nunes MA, Rubin MA, da Cruz IB, Barbisan F, Dressler VL, Pereira LB, Schetinger MR, Morsch VM, Gon lves JF, Mazzanti CM: Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na+, K + -ATPase activities. Physiol Behav 2014, 135:152?67. 31. Pari L, Murugavel P, Sitasawad SL, Kumar KS: Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: an in vivo and in vitro study. Life Sci 2007, 80:650?58. 32. Demir HA, Kutluk T, Ceyhan M, Yaci-K eli B, Aky C, Cengiz B, Varan A, Kara A, Yal n B, Se eer G, B pamuk M: Comparison of sulbactam-cefoperazone with carbapenems as empirical monotherapy for febrile neutropenic children with lymphoma and solid tumors. Pediatr Hematol Oncol 2011, 28:299?10. 33. Amara S, Douki T, Garrel C, Favier A, Ben Rhouma K, Sakly M, Abdelmelek H: Effects of static magnetic field and cadmium on oxidative stress andKim et al. BMC Complementary and Alternative Medicine 2014, 14:428 http://www.biomedcentral.com/1472-6882/14/Page 8 of34.35.36.37. 38.39. 40. 41.DNA damage in rat cortex brain and hippocampus. Toxicol Ind Health 2011, 27:99?06. Kanter M, Unsal C, Aktas C, Erboga M: Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicol Ind Health doi:10.1177/0748233713504810. Paniagua-Castro N, Escalona-Cardoso G, Madrigal-Bujaidar E, Mart ez-Galero E, Chamorro-Cevallos G: Protection against cadmium-induced teratogenicity in vitro by glycine. Toxicol In Vitro 2008, 22:75?9. Pari L, Murugavel P: Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 2007, 234:44?0. Minami A, Takeda A, Nishibaba D, Takefuta S, Oku N: Cadmium toxicity in synaptic neurotransmission in the brain. Brain Res 2001, 894:336?39. Luchese C, Brand R, de Oliveira R, Nogueira CW, Santos FW: Efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice. Toxicol Lett 2007, 173:181?90. Valko M, Morris H, Cronin MT: Metals, toxicity and oxidative stress. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 Curr Med Chem 2005, 12:1161?208. Quig D: Cysteine metabolism and metal toxicity. Altern Med Rev 1998, 3:262?70. Lu SC: Glutathione synthesis. Biochim Biophys Acta 2013, 1830:3143?153.doi:10.1186/1472-6882-14-428 Cite this article as: Kim et al.: Dendropanax morbifera L eille extract facilitates cadmium excretion and prevents.

Iron-starved cells at 26 (stationary and exponential phase, respectively; Table 4). The question

Iron-starved cells at 26 (stationary and exponential phase, respectively; Table 4). The question arose whether iron-starved Y. pestis cells activated a different metabolic route of pyruvate degradation able to produce reducing equivalents (NADHPieper et al. BMC Microbiology 2010, 10:30 http://www.biomedcentral.com/1471-2180/10/Page 12 of(Figure 4). FldA was identified in faint 2D spots and not reproducibly quantitated. PoxB activity measurements revealed excellent correlation between enhanced abundances and increased reaction rates in iron-starved cells. PoxB activities were 5.3-fold and 7.8-fold higher in lysates of iron-starved cells than in lysates of ironreplete cells at 26 (stationary and exponential phase, respectively; Table 4). Electron transport chains are localized in the IM, a fact that compromised the analysis of subunits of these IM protein complexes in 2D gels. NuoCD#99, a peripheral membrane protein of the NADH:ubiquinone oxidoreductase, was moderately decreased in abundance in iron-depleted cells (Figure 3). The E. coli NuoCD subcomplex is important for binding of some of the six Nuo-integrated Fe-S clusters [53]. Subunits of Fe-S cluster proteins with roles in two anaerobic energy metabolism branches were also less abundant in iron-depleted cells. This pertained to PflB#37 and YfiD#19, proteins of the formate-pyruvate lyase complex, and FrdA#6, which is part of the terminal electron acceptor fumarate reductase (Figure 4). Decreased abundances of metabolically active Fe-S cluster enzymes were a notable feature of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28854080 iron-starved Y. pestis proteome profiles, while the abundance and activity of PoxB suggested that this enzyme was important to maintain the aerobic energy metabolism and iron cofactor-independent generation of UQH2 in iron-deficient Y. pestis cells.Oxidative stress response in Y. pestis under iron starvation conditionsFigure 2 Protein display in 2D gels of Y. pestis KIM6+ periplasmic fractions in the pI range 6.5-9 (-Fe vs. +Fe conditions). Proteins were derived from cell growth in the presence of 10 M FeCl3 at 26 (top) or absence of FeCl3 at 26 (bottom). Gels (20 ?25 cm) were stained with CBB, with three gel replicates representing each group, and subjected to differential display analysis using the software Proteomweaver v.4.0. Protein assignment to a spot required validation by MS data from at least two representative gels. The denoted spot numbers are equivalent to those listed in Table 1 with their `-Fe vs. +Fe’ protein abundance ratios and other data.and UQH2 ) for the electron transport chain. Pyruvate oxidase (PoxB) degrades pyruvate to acetate and is a flavin-dependent, StatticMedChemExpress Stattic iron-independent enzyme that generates UQH 2 [52]. The pyruvate oxidase pathway indeed appeared to be important, as judged by the strong abundance increase of PoxB#39 (Figure 4) under -Fe conditions. The flavin cofactor may be recruited from redox activities of two flavodoxins. FldA3#44 was quite abundant and moderately increased in iron-depleted PD173074 web cellsOxidative stress is caused by various oxygen radicals and H2O2, and catalyzed by redox enzymes in non-specific reactions. While the presence of free intracellular iron aggravates oxidative stress via the Fenton reaction, it is mitigated by cytoplasmic proteins that scavenge free iron, e.g. Dps and the ferritins FtnA and Bfr [54]. The question arose how aerobically growing, iron-deficient Y. pestis cells coped with oxidative stress. One of the main E. coli global regulators of the oxida.Iron-starved cells at 26 (stationary and exponential phase, respectively; Table 4). The question arose whether iron-starved Y. pestis cells activated a different metabolic route of pyruvate degradation able to produce reducing equivalents (NADHPieper et al. BMC Microbiology 2010, 10:30 http://www.biomedcentral.com/1471-2180/10/Page 12 of(Figure 4). FldA was identified in faint 2D spots and not reproducibly quantitated. PoxB activity measurements revealed excellent correlation between enhanced abundances and increased reaction rates in iron-starved cells. PoxB activities were 5.3-fold and 7.8-fold higher in lysates of iron-starved cells than in lysates of ironreplete cells at 26 (stationary and exponential phase, respectively; Table 4). Electron transport chains are localized in the IM, a fact that compromised the analysis of subunits of these IM protein complexes in 2D gels. NuoCD#99, a peripheral membrane protein of the NADH:ubiquinone oxidoreductase, was moderately decreased in abundance in iron-depleted cells (Figure 3). The E. coli NuoCD subcomplex is important for binding of some of the six Nuo-integrated Fe-S clusters [53]. Subunits of Fe-S cluster proteins with roles in two anaerobic energy metabolism branches were also less abundant in iron-depleted cells. This pertained to PflB#37 and YfiD#19, proteins of the formate-pyruvate lyase complex, and FrdA#6, which is part of the terminal electron acceptor fumarate reductase (Figure 4). Decreased abundances of metabolically active Fe-S cluster enzymes were a notable feature of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28854080 iron-starved Y. pestis proteome profiles, while the abundance and activity of PoxB suggested that this enzyme was important to maintain the aerobic energy metabolism and iron cofactor-independent generation of UQH2 in iron-deficient Y. pestis cells.Oxidative stress response in Y. pestis under iron starvation conditionsFigure 2 Protein display in 2D gels of Y. pestis KIM6+ periplasmic fractions in the pI range 6.5-9 (-Fe vs. +Fe conditions). Proteins were derived from cell growth in the presence of 10 M FeCl3 at 26 (top) or absence of FeCl3 at 26 (bottom). Gels (20 ?25 cm) were stained with CBB, with three gel replicates representing each group, and subjected to differential display analysis using the software Proteomweaver v.4.0. Protein assignment to a spot required validation by MS data from at least two representative gels. The denoted spot numbers are equivalent to those listed in Table 1 with their `-Fe vs. +Fe’ protein abundance ratios and other data.and UQH2 ) for the electron transport chain. Pyruvate oxidase (PoxB) degrades pyruvate to acetate and is a flavin-dependent, iron-independent enzyme that generates UQH 2 [52]. The pyruvate oxidase pathway indeed appeared to be important, as judged by the strong abundance increase of PoxB#39 (Figure 4) under -Fe conditions. The flavin cofactor may be recruited from redox activities of two flavodoxins. FldA3#44 was quite abundant and moderately increased in iron-depleted cellsOxidative stress is caused by various oxygen radicals and H2O2, and catalyzed by redox enzymes in non-specific reactions. While the presence of free intracellular iron aggravates oxidative stress via the Fenton reaction, it is mitigated by cytoplasmic proteins that scavenge free iron, e.g. Dps and the ferritins FtnA and Bfr [54]. The question arose how aerobically growing, iron-deficient Y. pestis cells coped with oxidative stress. One of the main E. coli global regulators of the oxida.

Rthritis Rheum 2009, 60:1406-1415. 15. Pfander D, Cramer T, Swoboda B: Hypoxia andRthritis Rheum 2009,

Rthritis Rheum 2009, 60:1406-1415. 15. Pfander D, Cramer T, Swoboda B: Hypoxia and
Rthritis Rheum 2009, 60:1406-1415. 15. Pfander D, Cramer T, Swoboda B: Hypoxia and HIF-1 in osteoarthritis. Int Orthop 2005, 29:6-9. 16. Yudoh K, Nakamura H, Masuko-Hongo K, Kato T, Nishioka K: Catabolic stress induces expression of hypoxia-inducible factor (HIF)-1 in articular chondrocytes: involvement of HIF-1 in the pathogenesis of osteoarthritis. Arthritis Res Ther 2005, 7:R904-R914. 17. Husa M, Liu-Bryan R, Terkeltaub R: Shifting HIFs in osteoarthritis. Nat Med 2010, 16:641-644. 18. Ruiz-Romero C, Calamia V, Rocha B, Mateos J, Fern dez-Puente P, Blanco FJ: Hypoxia conditions differentially modulate human PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29045898 normal and osteoarthritic chondrocyte proteomes. J Proteome Res 2010, 9:3035-3045. 19. Cl igues V, Murphy CL, Guill MI, Alcaraz MJ: Haem oxygenase-1 induction reverses the actions of interleukin-1 on hypoxia-inducible transcription factors and human chondrocyte metabolism in hypoxia. Clin Sci (Lond) 2013, 125:99-108. 20. Jakob M, D arteau O, Sch er D, Hintermann B, Dick W, Heberer M, Martin I: Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro. J Cell Biochem 2001, 81:368-377. 21. Ball ST, Amiel D, Williams SK, Tontz W, Chen AC, Sah RL, Bugbee WD: The effects of storage on fresh human osteochondral allografts. Clin Orthop Relat Res 2004, 418:246-252. 22. Angele P, Yoo JU, Smith C, Mansour J, Jepsen KJ, Nerlich M, Johnstone B: Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res 2003, 21:451-457. 23. Holden P, Horton WA: Crude subcellular fractionation of cultured mammalian cell lines. BMC Res Notes 2009, 2:243. 24. Duval E, Leclercq S, Elissalde JM, Demoor M, Gal a P, Boum iene K: Hypoxia-inducible factor 1 inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the ZM241385 cost hypoxiainducible factor 1-dependent redifferentiation of chondrocytes. Arthritis Rheum 2009, 60:3038-3048. 25. Nishida Y, Knudson CB, Nietfeld JJ, Margulis A, Knudson W: Antisense inhibition of hyaluronan synthase-2 in human articular chondrocytes inhibits proteoglycan retention and matrix assembly. J Biol Chem 1999, 274:21893-21899. 26. Recklies AD, White C, Melching L, Roughley PJ: Differential regulation and expression of hyaluronan synthases in human articular chondrocytes, synovial cells and osteosarcoma cells. Biochem J 2001, 354:17-24. 27. Hashimoto K, Fukuda K, Yamazaki K, Yamamoto N, Matsushita T, Hayakawa S, Munakata H, Hamanishi C: Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide. Inflamm Res 2006, 55:72-77. 28. Yatabe T, Mochizuki S, Takizawa M, Chijiiwa M, Okada A, Kimura T, Fujita Y, Matsumoto H, Toyama Y, Okada Y: Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic chondrocytes. Ann Rheum Dis 2009, 68:1051-1058. 29. Julovi SM, Ito H, Nishitani K, Jackson CJ, Nakamura T: Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res 2011, 29:258-264. 30. Schrobback K, Malda J, Crawford RW, Upton Z, Leavesley DI, Klein TJ: Effects of oxygen on zonal marker expression in human articular chondrocytes. Tissue Eng Part A 2012, 18:920-933.Markway et al. Arthritis Research.

Rmatologic toxicity Rash was one of the most common nonhematologic AEsRmatologic toxicity Rash was one

Rmatologic toxicity Rash was one of the most common nonhematologic AEs
Rmatologic toxicity Rash was one of the most common nonhematologic AEs [24,25]. In the IRIS study, rash occurred in 34 , although grade 3-4 rash was infrequent (2 ). Pruritus (7 ) and AG-221MedChemExpress Enasidenib alopecia (4 ) were also noted in smaller numbers of patients [25]. In the DASISION trial, first-line dasatinib treatment resulted in fewer cases of rash compared with imatinib treatment (11 vs 17 ), with grade 3-4 rash occurring in 0 vs 1 , respectively. No rates were provided for pruritis or alopecia, suggesting that the frequencies were < 10 in both arms [12]. In the MDACC study, 58 of patients experienced "skin toxicity" (grouped term) with dasatinib, which was grade 3-4 in 2 . In addition, 8 experienced pruritus of which 2 was grade 3-4 [13]. Dermatologic toxicity seems to be more common with nilotinib than imatinib. In the ENESTnd trial, rash occurred in 31 taking nilotinib 300 mg BID, 36 taking nilotinib 400 mg BID, and 11 taking imatinib (grade 3-4 in < 1 vs 3 vs 1 , respectively). Pruritus was also more common in both nilotinib arms (15 with 300 mg BID and 13 with 400 mg BID) compared with imatinib (5 ), as was alopecia (8 with nilotinib 300 mg BID, 13 with nilotinib 400 mg BID, and 4 with imatinib) [14]. In single-arm trials of first-line nilotinib 400 mg BID, rash occurred in 49 (2 grade 3-4) of patients in the MDACC trial [15] and in 42 (5 grade 3) in the GIMEMA trial [4]. Pruritus also occurred in 21 of patients in the GIMEMA trial (4 grade 3). Gastrointestinal symptoms Nausea, diarrhea, and vomiting are common in patients receiving BCR-ABL inhibitor therapy, although recent data indicate that gastrointestinal (GI) disturbances occur less often in patients receiving dasatinib or nilotinib compared with those receiving imatinib. In the DASISION trial, nausea (8 v 20 ) and vomiting (5 vs 10 ) both occurred less frequently with dasatinib compared with imatinib, whereas rates of diarrhea were similar (17 in both arms). Grade 3-4 diarrhea was reported in < 1-1 , and no patients in either arm experienced grade 3-4 nausea or vomiting [12]. In the MDACC trial of dasatinib, higher rates of GI AEs were reported, including diarrhea in 53 (2 grade 3-4), nausea in 45 (0 grade 3-4), and vomiting in 21 (0 grade 3-4) [13]. In the ENESTnd trial, rates of GI AEs were lower with nilotinib 300 mg and 400 mg vs imatinib, including nausea (11 vs 19 vs 31 ), diarrhea (8 vs 6 vs 21 ), and vomiting (5 vs 9 vs 14 ), of which 0-1 were grade 3-4 cases in all arms [14]. In the MDACC study of first-line nilotinib, nausea and diarrhea were reported in 38 and 21 of patients, respectively, (no grade 3-4), and diarrhea occurred in 7 (2 grade 3-4) [15]. In the GIMEMA study, 11 of patientsexperienced nausea/vomiting (1 grade 3-4) and 7 had diarrhea (2 grade 3) [4].Edema Fluid retention is common with imatinib, as shown by 56 of patients receiving imatinib in the IRIS trial experiencing superficial edema and 13 having weight gain [25]. First-line dasatinib and nilotinib treatment are associated with lower rates of edema. In the DASISION, superficial edema (grouped term) was PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26024392 much less frequent with dasatinib (9 ) compared with imatinib (36 ), and rates of grade 3-4 superficial edema were low (0 vs < 1 , respectively) [12]. In the MDACC study of dasatinib, edema was reported in 32 of patients (no grade 3-4) [13]. In the ENESTnd trial, different types of edema were reported separately. In the nilotinib 300 mg BID, nilotinib 400 mg BID.

Transduction pathway required for biofilm development by Pseudomonas aeruginosa. J BacteriolTransduction pathway required for biofilm

Transduction pathway required for biofilm development by Pseudomonas aeruginosa. J Bacteriol
Transduction pathway required for biofilm development by Pseudomonas aeruginosa. J Bacteriol 2000, 182:425-431. 37. Kaur R, Macleod J, Foley W, Nayudu M: Gluconic acid: An antifungal agent produced by Pseudomonas species in biological control of take-all. Phytochemistry 2006, 67:595-604. 38. de Werra P, P hy-Tarr M, Keel C, Maurhofer M: Role of gluconic acid production in the regulation of biocontrol traits of Pseudomonas fluorescens CHA0. Appl Environ Microbiol 2009, 75:4162-4174.39. Takeuchi K, Kiefer P, Reimmann C, Keel C, Rolli J, Vorholt JA, Haas D: Small RNA-dependent expression of secondary metabolism is controlled by Krebs cycle function in Pseudomonas fluorescens. J Biol Chem 2009, 284:34976-34985. 40. Thomas-Chollier M, Sand O, Turatsinze JV, Janky R, Defrance M, Vervisch E, Brohe?S, van Helden J: RSAT: regulatory sequence analysis tools. Nucleic Acids Res 2008, 36:W119-W127. 41. Silby MW, Cerde -T raga AM, Vernikos GS, Giddens SR, Jackson RW, Preston GM, Zhang XX, Moon CD, Gehrig SM, Godfrey SAC, Knight CG, Malone JG, Robinson Z, Spiers AJ, Harris S, Challis GL, Yaxley AM, Harris D, Seeger K, Murphy L, Rutter S, Squares R, Quail MA, Saunders E, Mavromatis K, Brettin TS, Bentley SD, Hothersall J, Stephens E, Thomas CM, Parkhill J, Levy SB, Rainey PB, Thomson NR: Genomic and genetic analysis of diversity and plant interactions of Pseudomonas fluorescens. Genome Biol 2009, 10:R51. 42. Mathee K, Narasimhan G, Valdes C, Qiu X, Matewish JM, Koehrsen M, Rokas A, Yandava CN, Engels R, Zeng E, Olavarietta R, Doud M, Smith RS, Montgomery P, White JR, Godfrey PA, Kodira C, Birren B, Galagan JE, Lory S: Dynamics of Pseudomonas XAV-939 web aeruginosa genome evolution. Proc Natl Acad Sci USA 2008, 105:3100-3105. 43. Moynihan JA, Morrissey JP, Coppoolse ER, Stiekema WJ, O’Gara F, Boyd EF: Evolutionary history of the phl gene cluster in the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27607577 plant-associated bacterium Pseudomonas fluorescens. Appl Environ Microbiol 2009, 75:2122-2131. 44. Roy PH, Tetu SG, Larouche A, Elbourne L, Tremblay S, Ren Q, Dodson R, Harkins D, Shay R, Watkins K, Mahamoud Y, Paulsen IT: Complete genome sequence of the multiresistant taxonomic outlier Pseudomonas aeruginosa PA14. PLoS One 2010, 5:e8842. 45. Sarkar S, Guttman D: Evolution of the core genome of Pseudomonas syringae, a highly clonal, endemic plant pathogen. App Env Microbiol 2004, 70:1999-2012. 46. Rojo F, Dinamarca A: Catabolite repression and physiological control. In Pseudomonas: virulence and gene regulation. Volume 2. Edited by: Ramos JL. Kluwer Academic/Plenum Publishers; 2004:365-387. 47. Schultz JE, Matin A: Molecular and functional characterization of a carbon starvation gene of Escherichia coli. J Mol Biol 1991, 218:129-140. 48. Schultz JE, Latter GI, Matin A: Differential regulation by cyclic AMP of starvation protein synthesis in Escherichia coli. J Bacteriol 1988, 170:3903-3909. 49. Azam TA, Ishihama A: Twelve species of nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affininty. J Biol Chem 1999, 274:33105-33113. 50. Cases I, de Lorenzo V: The genomes of Pseudomonas encode a third HU protein. Micriobiology Comment 2002, 148:1243-1245. 51. P ez-Mart J, de Lorenzo V: The 54-dependent promoter Ps of the TOL plasmid of Pseudomonas putida requires HU for transcriptional activation in vivo by xylR. J Bacteriol 1995, 177:3758-3763. 52. Yuste L, Herv AB, Canosa I, Tobes R, Nogales J, P ez-P ez MM, Santero E, D z E, Ramos JL, de Lorenzo V, Rojo F: Growth phase.

D SScPAH patients is scarce, the results obtainedhere provide valuable exploratoryD SScPAH patients is scarce,

D SScPAH patients is scarce, the results obtainedhere provide valuable exploratory
D SScPAH patients is scarce, the results obtainedhere provide valuable exploratory information. However, they underscore the need for sampling of suitable tissue specimens in these patient groups for future research, also into receptor functionality studies. The majority of the PVOD samples were biopsies, while the samples from the SScPAH and IPAH group were derived from autopsy material. We cannot exclude some influence on results, as there is no knowledge on post-mortem behaviour of the (p)PDGFR-b and PDFG-B. Another influencing factor might be the fact that the biopsy group does not necessarily represent end-stage disease, in contrast to the explanation- and autopsy samples. How do we interpret these results? The pattern of immunoreactivity of PDGFR-b and probably pPDGFR-b in SScPAH, IPAH and PVOD follows the distinctOverbeek et al. Arthritis Research Therapy 2011, 13:R61 http://arthritis-research.com/content/13/2/RPage 11 ofArterioles100 Prevalence ( )Small vesselsVeins0 SScPAH IPAH PVOD Control SScPAH IPAH PVOD Control0 SScPAH IPAH PVOD ControlFigure 8 Number of cases with positive immunostaining for epidermal growth factor receptor (EGFR) in the intima of pulmonary vessels. A: arterioles, B: Small vessels, C: veins) in SScPAH, IPAH, PVOD and normal controls. No staining was observed in the capillaries. Small vessels: those arterioles and/or venules that cannot be distinguished as such by their anatomical localisationpatterns of histomorphologic vasculopathy between these disease groups [20]. The PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29072704 specific role of PDGFR in SScPAH vascular VorapaxarMedChemExpress Vorapaxar remodeling is further supported by either PDGF or PDGFR autoantibodies [44]. Such antibodies may induce signaling pathways, which eventually may lead to local intimal fibrosis. No differences in the small vessel- and post-capillary vasculature were seen between SScPAH and PVOD. As PVOD-like changes may be seen in SScPAH pulmonary vasculature [19,20] it can be speculated that SScPAH and PVOD share activation of PDGFR-b as a pathophysiologic determinant. The observation of PDGFR-b immunoreactivity, in both affected and non-affected vessels, might be interpreted as pointing towards longstanding pathogenetic involvement. pPDGFR-b and PDGF-B showed immunoreactivity in the pulmonary vasculature of the diseased patient group, with an increased prevalence as compared to controls. This supports the pathogenetic role of the PDGFR-b pathway in PAH. However, this study neither demonstrated clear parallels in staining patterns between PDGFR-b and pPDGFR-b nor PDGFB in the SScPAH group. This might be explained by transactivation of PDGFR-b, resulting in phosphorylation of the PDGFR-b [45]. The extent of involvement of the PDGFR-b- pPDGFR-b-signalling pathway in PAH pathogenesis and whether the role of this pathway is different in SScPAH as in IPAH, will need to be investigated in functional studies. PDGFR-b can be inhibited by imatinib, a TKR inhibitor that also has specificity for the Abl-related gene protein in the tyrosine fusion protein Bcr-Abl and c-kit. The effect of imatinib in SSc pathogenesis might be enhanced by its inhibitory effect on c-Abl, which is important for the induction of extracellular matrix components via TGF-b signaling [46,47]. TGF-b is amongthe most important pro-fibrotic SSc-mediators [67]. This, together with the findings in the present study support the rationale for PDGFR-b targeted therapy in SScPAH. The effects of such therapy might extend to EGFR via transactivation by PDGFR-.

C, although the Chi-squared measure is the smoothest for these simulations.C, although the Chi-squared measure

C, although the Chi-squared measure is the smoothest for these simulations.
C, although the Chi-squared measure is the smoothest for these simulations. The preceding experiments yield understanding of the comparative behaviour of exploratory and confirmatory approaches to period estimation as a function of the degree of periodicity in the underlying sequence. As discussed in the introduction, an important characteristic of confirmatory approaches is the extent to which they are able to detect the presence of periodicity that may bedegraded in one way or another. Since the problem of detection is generally dependent on the detection threshold chosen for a specific application, a conventional method of comparison is to calculate the receiver operator characteristic (ROC) curve (true positives vs. false positives) for each method. The results of the ROC simulation for eroded and approximately periodic sequence fragments can be seen in Figure 4. The results for approximately periodic sequences, shown for period-10 only, are slightly get Aprotinin simplistic, since if it is known or suspected a priori that the period-10 component may be approximate rather than exact, a more reasonable approach may be to also consider the strength of components with periods 9, 11 etc. Under these circumstances, the order of preference among the various techniques compared herein may differ from that suggested by the results in Figure 4. Interestingly, between the two panels in Figure 4, the order of effectiveness of the various methods is reversed. Since the difference between the significance measures is most marked for Figure 3, where the BWB performs close to the ideal behaviour for a period-10 detector, we selected the BWB for further experimental work. An explanation for the good performance of the CRB for approximate periodicity can be constructed along similar lines to that for Fourier-based methods in the periodicity degradation simulations above, since CRB is also Fourier-based. Although the CRB is very effective for1.0 0.8 Probability 0.g-statisticBWBChi-sqCRB0.0010 Cramer-Rao bound 0.0008 0.0006 0.0004 0.0.4 0.2 0.00 10 20 30 40 Percent Erosion 0.0 0.5 1.0 1.5 2.0 2.5 Standard Deviation0.Figure 3 Significance measures from the embedded IPDFT (g-statistic and BWB) for period-10 synthetic sequences of length N = 150. Sequences were either erosion of a perfect period-10 signal (top) or had periods Gaussian distributed about an expected value of period-10 (bottom).Epps et al. Biology Direct 2011, 6:21 http://www.biology-direct.com/content/6/1/Page 7 ofg-statistic1.BWBChi-sqApproximateCRBErodedIPDFTHybridTrue positive rateTrue positive rate0.0.6 0.0.4 0.0 0.8 0.6 0.2 0.2 0.4 0.6 0.8 False positive rate 0.0 0.2 0.4 0.6 0.8 False positive rate 1.0.4 0.0 0.Figure 4 ROC curves for confirmatory period detection of eroded (left) and approximate (right) synthetic period-10 sequences and randomly permuted sequences for embedded IPDFT (top) and embedded Hybrid PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28914615 (bottom).approximate periodicity, which occurs commonly in practise, the simulation constraint of an average period of 10 bp is artificial and probably overstates the practical utility of the measure somewhat.Analysis of Yeast Chip-chip dataThe yeast ChIP-chip data identified 73327 DNA sequences that are associated with nucleosomes in vivo versus their linker sequences. Lee et al. [37] further utilised the variance in association to classify the sequences into 31557 well-positioned or 41770 fuzzy nucleosomes. Since the regions identified by Lee et al differed in length, and statistical power of.

Vity [7]; according to some, the latter behave in several ways likeVity [7]; according to

Vity [7]; according to some, the latter behave in several ways like
Vity [7]; according to some, the latter behave in several ways like germ cells, and especially like sperm [218,219]. ENCODE may have helped to bring to light the exceptional genetic activity of the germline. It is also interesting that new genes have a strong bias of being expressed in the testis, whereas older genes have stronger and broader expression patterns [193,216,220,221]. To explain this bias, it has been suggested that new genes arise first in the sperm to serve sperm functions, and that later these genes are somehow coopted for somatic functions [216,221,222]. This has been called the “out of testis” hypothesis [216,221,222]. Two reasons have been given for why this happens in the sperm specifically: One is the existence of TP there.Interestingly, TP is used in this hypothesis in a manner not far from the above–it is seen there as a phenomenon that facilitates genetic evolutionary OPC-8212MedChemExpress Vesnarinone change–though its origin in the first place is not easily explained from this view. Second, it was assumed that the sperm are under much stronger pressure to evolve rapidly than other cells in the body, and are thus in “high demand” of new genes [212,216]. However, a main reason to think that these new genes really serve the sperm in its performing phenotype is that knockout of them disrupts the development of sperm. According to the traditional theory, which has only the performing phenotype, this evidence of functionality from knockout indeed means that these genes serve the sperm. But the theory proposed here predicts the existence of the writing phenotype, which raises the possibility that many (though not all) of what we think of as “new sperm genes” serving the sperm’s performing phenotype are not necessarily traditional “sperm genes” but are either genes with an evolving somatic function that are the locus of much writing activity or genes that belong to the body of the writing phenotype, and that disruption of them by knockout derails the writing system and makes it cause damage in the sperm cell (indeed, the sensitivity of sperm cells is well known). Thus, the observation that has led to the assumption that the sperm are under pressure for rapid evolutionary change, which has underlain the out-of-testis hypothesis in the first place, may not be only due to rapid evolution of the sperm performing phenotype. It could be that, to a notable degree, the sperm appears to be so rapidly evolving because of the writing activity in it and the evolution of this activity. Indeed, we may now note that, of the examples of adaptive evolution detected by dN/dS > 1 mentioned in [223], the first two (and in that sense prominent) categories of examples mentioned involve molecular environment interaction genes and rapid evolution of sperm, and both of these take on entirely new meaning according to the theory proposed here. Though much more data are needed on the material discussed in this section, one thing we need to notice is that the “working sperm” hypothesis has relevance beyond science. In 2001, Old [218] (see also [219]) suggested that cancer cells imitate germ cells and trophoblasts in several respects which appear to be part of the malignancy of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 the disease, including global hypomethylation, expression of cancer-testis (CT) antigens, expression of chorionic gonadotropin, downregulation of the major histocompatibility complex and immune evasion, and more. Indeed, cancer cells are exceptionally genetically active. We should ask, therefore, whether ac.

A FISH analysis. Nuclei are stained with DAPI.Preparation of CRKLA FISH analysis. Nuclei are stained

A FISH analysis. Nuclei are stained with DAPI.Preparation of CRKL
A FISH analysis. Nuclei are stained with DAPI.Preparation of CRKL targeting peptideIn this study, we used the peptides, which has been reported to be disrupted complexes between BCR-ABL and CRKL depend on the SH3 domain of CRKL in CML cells [26]. Peptides used in the experiments are followed: CRKL-targeting peptide; KKW KMR RNP FWI KIQ RC ?CGI RVV DNS PPP ALP PKR RRS APS PTR V, control peptide; KKW KMR RNP FWI KIQ RC ?CGI RVV DNS PPG ALG PLL RRS APS PTR V. The KKW KMR RNP FWI KIQ RC was the shuttle tag sequence performing a receptor-independent cell entry. The chimeric peptide was synthesized and purified by using reverse-phase high performance liquid chromatography (HPLC) (Toray Research Center, Otsu, Japan). Peptide stocks were prepared in DMSO and stored in aliquots at -80 .Statistical analysisanalyses. P values less than 0.05 were considered statistically significant.ResultsIdentification of CRKL amplification in gastric cancerThe statistical analysis was performed using an unpaired t-test, chi-square test, or Dunnett’s test. JMP version 7.0.1 software (SAS Institute, Cary, NC) was used for theTo search for highly amplified genes in gastric adenocarcinoma, we adopted a genome-wide high-resolution SNP microarray approach in three cell lines of differentiated gastric adenocarcinoma: MKN7, MKN28, and MKN74. Genotype calls were obtained at more than 95 of the 262,264 SNP sites on the array, meaning that the SNP microarray analysis had been performed properly. The SNP microarray data were then used to determine the chromosomal copy number using the CNAG program (Figures 1A and 1B). Five highly amplified regions with a copy number of more than 6 (9p13, 17q12-q21, 19q12, 19q13, and 22q11) were identified, as shown in Table 1. These regions contained various kinds of genes, a total of 22 genes (Table 1). Among them, we decided to focus on the CRKL gene at chromosome PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28212752 22q11.21, the productNatsume et al. Journal of Translational Medicine 2012, 10:97 http://www.translational-medicine.com/content/10/1/Page 6 ofFigure 4 (See legend on next page)of which is an SH2 and SH3 domain-containing adaptor protein that shares homology with the CRK oncoprotein, because CRKL is a known substrate of BCR-ABL kinase in Philadelphia chromosome-positive leukemia [27,28] and its role in gastric cancer has not been previously analyzed. To confirm that CRKL gene amplification was detectable in the MKN74 cell line, we performed a FISH analysis using a probe specific for CRKL. As expected, an extreme increase in the CRKL copy number was detected in the MKN74 cells using aFISH analysis (Figure 1C). When the level of CRKL mRNA expression was examined in MKN74 cells using a real-time QRT-PCR analysis, the level was much higher than that in non-cancerous gastric tissue (Figure 1D). Moreover, a western blot analysis showed that the level of CRKL protein expression was higher in MKN74 cells than in non-cancerous gastric tissue (Figure 1E). These results suggested that the CRKL gene is highly amplified and that CRKL is overexpressed in a subset of gastric cancer cell lines.Natsume et al. Journal of Translational Medicine 2012, 10:97 http://www.translational-medicine.com/content/10/1/Page 7 of(See figure on previous page) Figure 4 Responses of the MKN74 gastric cancer cell line with CRKL amplification to treatment with BMS354825 (a dual Src/BCR-ABL kinase inhibitor) and CRKL-targeting peptide. (A) Viability of MKN74 cells Avermectin B1a cost treated with BMS354825 but not those treated with AM.

Cells to find the rare outstanding performers (17 minutes at 1000 cells perCells to find

Cells to find the rare outstanding performers (17 minutes at 1000 cells per
Cells to find the rare outstanding performers (17 minutes at 1000 cells per second). With the modern high speed sorters this will take less than a minute. In the following, utilization of cell sorting in biotechnology will therefore be highlighted with the main emphasis on AICAR custom synthesis fluorescence activated cell sorting. The actual selection of single cells is achieved by different types of sorters, the most frequently used ones being jet-in-air sorters. The liquid stream with the cells, after passing the laser light and the optics, is split up into defined droplets. The droplets containing a cell to be sorted is charged and then deflected into either a separate tube or directly into the individual wells of a microtiter plate. Table 1 provides an overview of typical applications of cell sorting in biotechnology.sorting allows a more in depth characterization of cells with specific properties observed in flow cytometric analyses, by sorting cells from different observed subpopulations. Subsequently, these cells are analyzed by other methods, thus linking different types of information and analytical methods to enhance the understanding of cell behavior. Cell viability is probably the most widely used parameter in this respect. A comprehensive study of viability assessment by flow cytometry and cell sorting has been described by Nebe-von Caron et al. [7]. By triple fluorochrome staining using propidium iodide, ethidium bromide and bis-oxonol, it is possible to discriminate between undamaged, damaged (membrane depolarized) and dead cells, which was verified by sorting and plating of the different subpopulations. Similar approaches have been followed for lactic acid PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28607003 bacteria [8,9], further underlying the validity of fluorescent viability staining. ComasRiu and Vives-Rego extended this concept for Paenibacillus polymyxa by including the forward scatter signal into the assessment, thus discriminating between live and dead vegetative cells as well as viable and non-viable endospores [10]. Using a similar approach as described above for bacteria, the utility of flow cytometric viability assessment was verified for baker’s yeast by sorting and plating [11]. M ler and L che analyzed populations of brewing yeast for the content of DNA, neutral lipids and hydroxysterol by flow cytometry, verifying the data with cell sorting and image analysis [12]. Petit et al. described the use of cell sorting (combined with flow cytometry and confocal microscopy) for the study of respiratory dysfunction in yeast [13]. During the last years the distribution of cellular properties, as observed by flow cytometry, and the sorting of specific subpopulations have attracted additional attention for transcriptomic studies. Many biological samples are cell mixtures, and it was shown that sorting the differ-Physiological researchFlow cytometry, but also cell sorting have become valuable tools for physiological research in biotechnology. CellPage 3 of(page number not for citation purposes)Microbial Cell Factories 2006, 5:http://www.microbialcellfactories.com/content/5/1/ApIII pVIIIBOmpA OM PG PP CMCSpA PG CMDcell wall protein e.g. AgEAga2 AgaFCW CMCWCMgp64 nucleocapsid lipid envelopeCMFigure 2 Pro- and eukaryotic surface display systems Pro- and eukaryotic surface display systems. A: phage display, e.g. phage M13. pIII: minor capsid protein, pVIII: major capsid protein [19]. B: gram negative bacteria, e.g. E. coli. Anchor protein: OmpA, CM: cytoplasma membrane, OM: outer membrane, PP:.

An ?SD of three individual experiments. *p < 0.05, **p < 0.01, ***p < 0.001

An ?SD of three individual experiments. *p < 0.05, **p < 0.01, ***p < 0.001 vs control
An ?SD of three individual experiments. *p < 0.05, **p < 0.01, ***p < 0.001 vs control group (Student's t test)induction of TNF and MCP-1 expression was attenuated in cells transfected with ATF4 siRNA but not in cells transfected with si-Con. These findings underscored the role of ATF4 in cocaine-mediated induction of microglial activation. We next sought to enquire whether cocaine could also mediate nuclear translocation of ATF4 resulting ultimately in increased transcription of TLR2. BV2 cells were exposed to cocaine for varying time points (0 to 6 h) followed by assessment of ATF4 translocation in the nuclear fractions. As shown in Fig. 5d, e, exposure of BV2 cells to cocaine resulted in a time-dependent increase in translocation of ATF4 into the nucleus with a maximal response at 1 h (2.3-fold, p = 0.0013) and a concomitant decrease in the cytoplasm. It is well-recognized that nuclear translocation of transcription factors is necessary for accessing and binding to the promoter region of a gene. Intriguingly, using the TFSEARCH software we found a predicted ATF4 binding site in the intron of the gene instead of its presence at a traditional promoter site upstream of the transcription start site. This led to a speculation that ATF4 could be binding to the intronic promoter of the TLR2 gene. Adding credence to this hypothesis are reports identifying an intronic promoter in the murine proteinase 3 gene [42] and another report that described the binding of ATF4 to an intronic promoter leading, in turn, to regulated expression of Siah2 mRNA in response to ERstress [43]. Interestingly, ATF4-binding site is also present in the first intron of the human VEGFA gene [44]. To assess whether cocaine mediated the binding of ATF4 to the intronic region of TLR2, we performed the ATF4 ChIP assay. BV2 cells were treated with cocaine for 1 h followed by RNA extraction and processed using a ChIP assay kit. As shown in Fig. 5f, exposure of BV2 cells to cocaine resulted in enhanced binding of ATF4 to the TLR2 intronic promoter.TLR2 phosphorylation, NF-B translocation, and MyD88 are involved in cocaine-mediated microglial activationHaving demonstrated that cocaine mediated up-regulation of TLR2 protein and microglial activation, we next sought to examine whether cocaine could also PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27107493 activate the TLR2 signaling pathway(s) leading, in turn, to downstream activation of microglia. To explore the possibility that cocaine exposure could also increase phosphorylation of TLR2, lysates from cocaine-exposed BV2 cells were immunoprecipitated with TLR2 antibody and subsequently assessed for TLR2 tyrosine phosphorylation using the specific tyrosine antibody 4G10. As shown in Fig. 6a, cocaine-induced phosphorylation of TLR2 was Stattic custom synthesis observed as early as 15 min after cocaine exposure with a peak at 30 min. Next, we sought to investigate whether cocaine could also promote nuclear translocation of NF-B. For this, following exposure of BV2 cells to cocaine, cytosolic and nuclear protein extracts were monitored for levels of NF-B at theLiao et al. Journal of Neuroinflammation (2016) 13:Page 11 ofFig. 6 Cocaine-mediated induction of phosphorylation-dependent TLR2 signaling pathway and microglial activation. a Cocaine-mediated induction of phosphorylation of TLR2 in BV2 cells. b Cocaine-mediated induction of NF-B nuclear translocation in BV2 cells. c siRNA transfection was used to knock down Myd88. Myd88 siRNA but not si-Con inhibited cocaine-mediated induction of IL-6, MCP-1, and T.

Ological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis.Ological recovery and antiretroviral therapy

Ological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis.
Ological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006;6:280?. Touloumi G, Pantazis N, Stirnadel HA, Walker AS, Boufassa F, Relugolix biological activity Vanhems P, et al. Rates and determinants of virologic and immunological response to HAART resumption after treatment interruption in HIV-1 clinical practice. J Acquir Immune Defic Syndr. 2008;49:492?. Mussini C, Cossarizza A, Sabin C, Babiker A, De Luca A, Bucher HC, et al. Decline of CD4(+) T-cell count before start of therapy and immunological response to treatment in antiretroviral-naive individuals. AIDS. 2011;25:1041?. Mocroft A, Phillips AN, Gatell J, Ledergerber B, Fisher M, Clumeck N, et al. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet. 2007;370:407?3. Ledergerber B, Lundgren JD, Walker AS, Sabin C, Justice A, Reiss P, et al. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet. 2004;364:51?2.27. Lifson AR, Krantz EM, Eberly LE, Dolan MJ, Marconi VC, Weintrob AC, et al. Long-term CD4+ lymphocyte response following HAART initiation in a U.S. Military prospective PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 cohort. AIDS Res Ther. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26104484 2011;8:2. 28. Pakker NG, Notermans DW, De Boer RJ, Roos MT, De Wolf F, Hill A, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998;4:208?4. 29. El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283?6. 30. Mussini C, Touloumi G, Bakoyannis G, Sabin C, Castagna A, Sighinolfi L, et al. Magnitude and determinants of CD4 recovery after HAART resumption after 1 cycle of treatment interruption. J Acquir Immune Defic Syndr. 2009;52:588?4. 31. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203. 32. Cozzi-Lepri A, French MA, Baxter J, Okhuysen P, Plana M, Neuhaus J, et al. Resumption of HIV replication is associated with monocyte/macrophage derived cytokine and chemokine changes: results from a large international clinical trial. AIDS. 2011;25:1207?7. 33. Deeks SG, Kitchen CM, Liu L, Guo H, Gascon R, Narvaez AB, et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004;104:942?. 34. Roberts L, Passmore JA, Williamson C, Little F, Bebell LM, Mlisana K, et al. Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression. AIDS. 2010;24:819?1. 35. Sax PE, Tierney C, Collier AC, Fischl MA, Mollan K, Peeples L, et al. Abacavirlamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009;361:2230?0. 36. Le T, Wright EJ, Smith DM, He W, Catano G, Okulicz JF, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med. 2013;368:218?0. 37. Persaud D, Gay H, Ziemniak C, Chen YH, Piatak Jr M, Chun TW, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013;369:1828?5.Submit your next manuscript to BioMed Central and take full advantage of:?Convenient online submission ?Thorough peer review ?No space constraints.

Nd cell proliferation in polycystic Vadadustat clinical trials ovarian syndrome. Hum Reprod 1996, 11:1387?392. 34.

Nd cell proliferation in polycystic Vadadustat clinical trials ovarian syndrome. Hum Reprod 1996, 11:1387?392. 34. Cheng G
Nd cell proliferation in polycystic ovarian syndrome. Hum Reprod 1996, 11:1387?392. 34. Cheng G, Weihua Z, M inen S, M el?S, Saji S, Warner M, Gustafsson JA, Hovatta O: A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary. Biol Reprod 2002, 66:77?4. 35. Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA: Androgen stimulate early stages of follicular growth in the primate ovary. J Clin Invest 1998, 101:2622?629. 36. Leung PC, Armstrong DT: Interactions of steroids and gonadotropins in the control of steroidogenesis in the ovarian follicle. Annu Rev Physiol 1980, 42:71?2. 37. McNatty KP, Smith DM, Makris A, Osathanondh R, Ryan KJ: The microenvironment of the human antral follicle: interrelationships among the steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro. J Clin Endocrinol Metab 1979, 49:851?60. 38. Westergaard L, Christensen IJ, McNatty KP: Steroid levels in ovarian follicular fluid related to follicle size and health status during the normal menstrual cycle in women. Hum Reprod 1986, 1:227?32.doi:10.1186/1757-2215-5-26 Cite this article as: Li et al.: Immunoreactivities of androgen receptor, estrogen receptors, p450arom, p450c17 proteins in wild ground squirrels ovaries during the nonbreeding and breeding seasons. Journal of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28506461 Ovarian Research 2012 5:26.Submit your next manuscript to BioMed Central and take full advantage of:?Convenient online submission PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 ?Thorough peer review ?No space constraints or color figure charges ?Immediate publication on acceptance ?Inclusion in PubMed, CAS, Scopus and Google Scholar ?Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit
Hayashi et al. Journal of Ovarian Research 2012, 5:31 http://www.ovarianresearch.com/content/5/1/RESEARCHOpen AccessDienogest increases the progesterone receptor isoform B/A ratio in patients with ovarian endometriosisAtsushi Hayashi, Akiko Tanabe*, Sachiko Kawabe, Mika Hayashi, Hiroko Yuguchi, Yoshiki Yamashita, Kiyoji Okuda and Masahide OhmichiAbstractBackground: The resistance of endometriotic tissue to progesterone can be explained by alterations in the distribution of progesterone receptor (PR) and estrogen receptor (ER) isoforms. The aims of this study were to examine the expressions of PR-A, PR-B, ER and ER in endometrioma and assess whether these expressions are affected by dienogest or leuprolide acetate (LA) treatment. Methods: We enrolled 60 females, including 43 patients with endometriosis (14 who received no medical treatment, 13 who received dienogest and 16 who received LA before undergoing laparoscopic surgery) and 17 patients with leiomyoma. The expression levels of PR and ER isoforms in eutopic and ectopic endometrium were assayed with quantitative real-time PCR, and confirmed with immunohistochemistry. Results: A decreased PR-B/PR-A ratio and an increased ER/ER ratio were demonstrated in ectopic endometrium derived from females with endometriosis compared with the ratios observed in eutopic endometrium obtained from females without endometriosis. Although LA treatment did not affect the PR-B/PR-A and ER/ER ratios, dienogest treatment increased the PR-B/PR-A ratio and decreased the ER/ER ratio in patients with endometriomas. Conclusions: Dienogest may improve progesterone resistance in endometriotic tissue by increasing the relative expressions of PR-B and PR-A, and decreasing the relative ex.

N factor in 2004 [1] and acts within the post-entry, pre-integration window [2,3]. TheN factor

N factor in 2004 [1] and acts within the post-entry, pre-integration window [2,3]. The
N factor in 2004 [1] and acts within the post-entry, pre-integration window [2,3]. The viral molecular target of TRIM5 is the correctly matured N-terminal domain of capsid (CA) proteins forming the outer surface of the retroviral core [2,4-8]. A direct interaction between the two proteins, each present as high molecular weight multimers, occurs shortly after entry and is required for downstream inhibition of viral replication [8-12]. The mechanism of TRIM5-mediated restriction can be broken down to discrete events, some of them inter-dependent: (i) virus entrapment into TRIM5 cytoplasmic bodies [13], (ii) decreased stability of the virus core [8,14-16], (iii) targeting to a proteasome-dependent degradation pathway [17-20], and (iv) inhibition of nuclear transport [17,21,22]. CypA, a host peptidyl-prolyl cis/trans isomerase that is ubiquitously expressed in tissues, is known to play roles in both HIV-1 infection of human cells and in HIV-1 restriction by TRIM5 in monkey cells. In dividing permissive human cells, CypA enhances HIV-1 infectivity by regulating the disassembly of its core [23-25] independently of TRIM5 [26,27]. On the other hand, restriction of HIV-1 by simian TRIM5 orthologues is enhanced by CypA, and inhibition of CypA expression or of its activity partially rescues infectivity in restrictive conditions [21,26,28-30]. CypA binds to an exposed proline-rich loop on buy Aviptadil pubmed ID:https://www.ncbi.nlm.nih.gov/pubmed/25447644 the viral CA [31,32] and catalyzes the isomerisation of the peptide bond G89-P90 [33,34]. The mutation V86M in the CypA-binding loop of HIV-1 CA has been identified as conferring partial resistance to TRIM5rh [35]. The mechanism of HIV-1 resistance to TRIM5rh conferred by V86M CA was not addressed in this study. However, it was established that this mutation in the CypA-binding loop did not disrupt CA-CypA interactions in vitro or in cell cultures [35]. We and others have proposed that point mutations in the variable region 1 (v1) of TRIM5hu could confer HIV-1 restriction capability [36-41]. These mutations were discovered by mapping of HIV-1 restriction determinants in non-human TRIM5 orthologues [36,39-41] or through the use of random mutagenesis-based screens [38,42]. Such antiviral genes are promising candidates for gene therapy applications, owing to a few key characteristics: (i) They block replication early after virus entry and before integration can occur; (ii) They are human-like and thus probably nonimmunogenic; (iii) PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27484364 They inhibit HIV-1 by a well-established, natural mechanism with little side effect expected. However, it is currently unknown whether HIV-1 can acquire resistance to TRIM5hu mutants. Here we investigate the extent and mechanism of resistance of the HIV-1 CA mutant V86M to R332GR335G TRIM5hu and other mutants of the v1 domain. Our data show that this mutation affects physical andfunctional interactions with CypA in order to decrease HIV-1 sensitivity to TRIM5 while retaining replicationenhancement functions also conferred by CypA binding.ResultsCA-V86M HIV-1 is partially resistant to restriction by TRIM5hu mutant R332G-R335GWe analyzed whether V86M could protect HIV-1 against restriction by TRIM5hu mutant R332G-R335G in human TE671, human Sup-T1 and feline CRFK cells. The choice of human cells as an experimental model was justified by the need to gather data in cells representative of the HIV1 natural host, while the analysis in cat cells was prompted by the absence of an endogenous TRIM5 protein in this species, thus allowing us to analyz.

Rporated several new safety features that include removing the Gag/Gag-PolRporated several new safety features that

Rporated several new safety features that include removing the Gag/Gag-Pol
Rporated several new safety features that include removing the Gag/Gag-Pol frameshift, splitting the Gag, PR, and reverse transcriptase/integrase (RT/IN) functions onto separate plasmids, and greatly reducing the nucleotide sequence overlap between vector and Gag and between Gag and Pol. As part of the construction of this novel system, we used a truncated form of the accessory protein Vpr, which binds the P6 region of Gag, as a vehicle to deliver both PR and RT/IN as fusion proteins to the site of viral assembly and budding. We also replaced wt PR with a slightly less active T26S PR mutant in an effort to prevent premature processing and cytoxicity associated with wt PR. This novel “supersplit” packaging system yielded lentiviral titers comparable to those generated by conventional lentiviral packaging where Gag-Pol is supplied intact (1.0 ?106 TU/ml, unconcentrated). Conclusion: Here, we were able to create a true “split-function” lentiviral packaging system that has the potential to be used for gene therapy applications. This novel system incorporates many new safety features while maintaining high titers. In addition, because PR is supplied in trans, this unique system may also provide opportunities to examine viral protein processing and maturation.BackgroundThe genome of Human Immunodeficiency Virus Type 1 (HIV-1) is complex in that it employs overlapping reading frames to encode two essential polyproteins known asGag and Gag-Pol. The Gag polyprotein precursor supplies the structural components of the virus that include the matrix (MAp17), capsid (CAp17), nucleocapsid (NCp7), and p6 proteins while the Pol polyprotein precursor sup-Page 1 of(page number not for citation purposes)Retrovirology PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27324125 2007, 4:http://www.retrovirology.com/content/4/1/plies the viral enzymes protease (PR, p11), reverse transcriptase/Rnase H (RT, p66/p51), and integrase (IN, p32) (for review see [1,2]). The concentrations of Gag to Gag-Pol polyproteins are maintained at a ratio of 20:1 through a frameshift mechanism in which the ribosome slips by -1 on a heptanucleotide AU rich sequence located at the end of the NCp7 protein [3]. The ensuing frameshift results in the ribosome reading through P6 to produce the full length Gag-Pol polyprotein. This 20:1 ratio of the Gag to Gag-Pol has been shown by many researchers to be critical for the production of “infectious” viral particles. Attempts to vary the 20:1 polyprotein ratio, has resulted in BAY1217389 cost decreases in virus infectivity and stability [4-6]. In addition, the expression of Gag without Gag-Pol has been shown to result in the assembly of particles that are noninfectious [7], and in the reverse case, when Gag-Pol is expressed without Gag, there is efficient PR processing but no production of virions [8]. PR is essential for the processing of the viral polyprotein precursors and thus plays an important role in the maturation of viral particles and in the production of infectious particles [9-12]. During the assembly of the Gag and GagPol polyproteins, PR is initially inactive. As the concentration of polyproteins increases and the virion components are confined in the budding particle, PR then dimerizes and becomes active [13-16]. Once PR is active, it then sequentially cleaves the assembled precursor polyproteins resulting in the transformation of the immature viral particle into a mature infectious virion [10,12]. Hence, the correct balance of Gag to Gag-Pol is PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28212752 critical to ensure that not only the viral enzymes are.

Old) (Figure 4A, lower panel). This phenomenon represents an experimental caseOld) (Figure 4A, lower panel).

Old) (Figure 4A, lower panel). This phenomenon represents an experimental case
Old) (Figure 4A, lower panel). This phenomenon represents an experimental case in which integration inhibition does not systematically lead to strong 2-LTRc accumulation. Indeed, in the TL3.4 cells, 2-LTRc accumulation was observed only with RAL treatment or D116N (Figure 4A, lower panel). This also suggests that LEDGF/p75 is not an essential factor for 2-LTRc formation. It is important to note that the inhibition of the remaining integration between conditions of TL3.4 infected with WT, and TL3.4 infected with D116N or in the presence of RAL (Figure 4A, upper panel, columns 3 and 4), cannot explain the difference of 2-LTRc accumulation in these conditions of infection (Figure 4A, lower panel, columns 3 and 4). Indeed, the observed 7-fold decrease in integration is expected PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28945807 to display 85 of maximal 2-LTRc accumulation based on the correlation shown in Figure 1D. Moreover, as described previously in other cell lines, RAL reversal produced a fall in the percentage of 2-LTR circles in both cell lines (Additional file 1: Figure S8). These results indicate that when integration is inhibited without blocking IN catalytic competence (i.e. in the absence of LEDGF), the inhibition is not necessarily associated with 2-LTRc accumulation since IN is still competent to GW0742 cost cleave 2-LTRc (see model in Figure 4B). Accordingly, inhibiting the catalytic activity of IN (RAL treatment or D116N infection) leads to accumulation of 2-LTRc due to the inability of IN to cleave these circular DNA forms. Our data imply that IN plays a key role in controlling the balance between the amounts of DNAL PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27484364 and 2-LTRc through direct effects on 2-LTRc – > DNAL conversion. In this context, RAL removal leads to 2LTRC cleavage, which in turn produces new DNAL that can integrate and support resumption of viral replication. Taken together with the above-mentioned observation of new DNAL forms after RAL removal, our data indicate that IN catalytic activity is directly involved in the 2-LTRc – > DNAL conversion.Thierry et al. Retrovirology (2015) 12:Page 7 ofFigure 4 2-LTRc are related to the IN catalytic activity. Cells expressing (TC3) or depleted (TL3.4) of LEDGF/p75 were infected with NLENG1-ES-IRES-WT +/- 500 nM RAL or NLENG1-ES-IRES-D116N. (A) Percentage of integration efficiency (upper panel) and 2-LTRc (lower panel) at d3 post-infection for both cell lines. Results are representative of four independent experiments; p value is reported in the histogram. (B) Model explaining the modulation of 2-LTRc amount in different contexts: LEDGF+ (TC3) or LEDGF- (TL3.4) with IN+ (WT) or IN- (D116N or WT + RAL). The numbers above the bars in panel A are related to the corresponding model in panel B.Integrase is found at the palindromic junction of 2-LTRcThe IN-dependent conversion of 2-LTR circles into DNAL implies that IN should be physically present at the palindromic junction. It has been demonstrated by Bukrinsky and collaborators that HIV-1 IN was not detected in association with 2-LTRc [27]. Importantly, this result was obtained under condition where no 2-LTRc accumulation was observed (i.e. WT infection in the absence of any INSTI compound). We then performed ChIP (chromatin immunoprecipitation) experiments to assess the presence of IN on 2-LTRc within cells under 2-LTRc accumulation conditions at 24 and 72 hours post-infection. According to Bukrinsky’s study [27], IN was not found at the palindromic junction during WT infection (Figure 5), probably due to the small amount of 2-LT.

D 100 M FeSO4 for 8 hours. Then, after removal of H2OD 100 M FeSO4

D 100 M FeSO4 for 8 hours. Then, after removal of H2O
D 100 M FeSO4 for 8 hours. Then, after removal of H2O2 and FeSO4, cells were cultured in DMEM/F12 medium containing 10 Heshouwuyin-containing serum for 72 hours. The protective effect of Heshouwuyin on the aging of Leydig cells in the testes was observed. The -galactosidase staining kit was used, which purchased from Genmed Scientifics Inc., USA(GMS10010.1). According to the experimental requirements, the Leydig cells were cultured primarily using Petri dishes. After the culture medium was aspirated, the cells were washed twice with 0.1 M PBS, and fixed using 1 mL -galactosidase fixative for 15 minutes. Then, the fixative was aspirated, and the cells were washed with 0.1 M PBS three times for 3 minutes each. -galactosidase dye working solution was added, 1 mL per well, along with 10 L A solution, 10 L B solution, 930 L C solution, and 50 L X-Gal solution. Cells were incubated at 37 overnight. The six-well plates were covered with plastic wrap to prevent evaporation. Then, the working fluid was removed. Under the optical microscope (Leica DM 6000 M, Germany), the cytoplasm of -galactosidase positive cells was blue. The number of blue cells out of 200 cells was observed and recorded. The SP600125 site experiments were repeated five times for robust statistical analysis.Fluorescence immunocytochemistry for observation of StAR and P450scc expression -galactosidase enzyme assayH2O2 and FeSO4 solutions, at a final concentration of 50 M and 100 M, respectively, were added into the six-well culture plates containing Leydig cells cultured for 48 hours. After culture 8 hours, H2O2 and FeSO4 were removed. Then, the cells were placed in DMEM/ F12 containing 10 fetal bovine serum for 72 hours.Sterilized 20 mm coverslips were placed in 90 mm Petri dishes. The cells were seeded in the Petri dishes at density of 2 ?104/mL. The corresponding treatment was given in each group. Samples were fixed in 4 paraformaldehyde for 30 minutes, incubated in 0.5 Triton X-100 for 20 minutes, and cultured in 3 H2O2 for 15 minutes toNiu et al. BMC Complementary and Alternative Medicine 2014, 14:250 http://www.biomedcentral.com/1472-6882/14/Page 5 ofeliminate endogenous peroxidase activity. The samples were rinsed with 0.1 M PBS three times for 2 minutes each before each experimental procedure. After rinsing with 0.1 M PBS three times for 2 minutes each, normal goat serum was added, and the samples were inoculated at 37 for 30 minutes. Filter paper was used to absorb the serum. Diluted rabbit anti-StAR, P450scc monoclonal antibody (1:100; Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) was added and incubated with samples at 4 overnight. Then, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25636517 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 samples were rinsed with PBS three times, for 5 minutes each. Fluorescent dye-labeled secondary antibody working solution (goat anti-rabbit IgG, Santa Cruz) was added and incubated with samples at 37 in darkness for 30 minutes. Green granules in the cytoplasm were observed under the fluorescence microscope, and the number of positive cells out of 200 cells was recorded. The experiments were repeated five times for robust statistical analysis.Western blot assay for determination of StAR and P450scc protein expression in Leydig cellsCultured cells in each group were digested with 0.25 trypsin and centrifuged to remove the supernatant. The total protein of each sample was quantified by a BCA protein assay kit. In each group, 50 g Leydig cell proteins were mixed with loading buffer, placed in a boiling water bath for 5?0 minutes and co.

S a successful approach for infertile couples, which commonly overcomes theS a successful approach for

S a successful approach for infertile couples, which commonly overcomes the
S a successful approach for infertile couples, which commonly overcomes the underlying infertility causes resulting in significantly PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28298493 higher pregnancy PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27872238 rates compared to natural conception. The variability in patient characteristics is directly related to the response to ART treatment, which consequently dictates the need* Correspondence: [email protected] Division of Human Reproduction, IVF Unit, 1st Department of Obstetrics and Gynaecology, Thonzonium (bromide) solubility Alexandra Hospital, Athens University Medical School, Athens, Greecefor reliable, personalized diagnostic and therapeutic approaches to optimize efficacy, as well as safety outcomes. Significant scientific discoveries have made the causes of infertility more apprehensible and ART has facilitated the development of increasingly complex diagnostic tools, prognostic models and treatment options. As a result, it is crucial to extend investigation to more genetic factors, not necessarily related directly to the reproductive system, such as runt-related transcription factor 2 (RUNX2) gene, in order to conclude whether or not they are involved in the outcome of ART treatment [1].?2012 Papamentzelopoulou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Papamentzelopoulou et al. Reproductive Biology and Endocrinology 2012, 10:99 http://www.rbej.com/content/10/1/Page 2 ofRUNX2 (Cbfa1, AML-3, PEBP2A) is well known for regulating both intramembranous and endochondral bone formation, as well as osteoblast development and differentiation and chondrocyte differentiation. It is a member of the runt family of transcription factors. The three mammalian RUNX proteins (RUNX1, RUNX2, RUNX3) share a highly conserved 128 amino acid DNA binding domain [2]. RUNX2 gene is located on chromosome 6, consists of eight coding exons and spans a genomic region of 130 kb. It contains a DNA-binding domain, a region of glutamine and alanine repeats in the N-terminal region and a region rich in proline-serinethreonine, which is necessary for transcriptional activation of target genes [3]. Moreover, RUNX2 association with the nuclear domain facilitates interaction with many co-regulatory proteins and chromatin-modifying complexes for the regulation of gene transcription [4]. In general, RUNX2 has been shown to play a crucial role in cell differentiation. Its expression has been recently identified in the rat ovary, but little is known about the regulatory mechanism of RUNX2 expression and the specific function of this protein in the human ovary. RUNX2 mRNA levels were shown to be increased by the luteinizing hormone (LH) surge in preovulatory follicles and newly forming corpus luteum in women and rodents, as determined by real time PCR, in situ hybridization, and human microarray analyses [5,6]. As a result, the LH-surge induced RUNX2 is functionally linked to various aspects of luteal development by regulating the expression of luteal specific genes. Moreover, in a model of doxycyline-inducible, triple transgenic mice (CMV-Cre;ROSA26 neoflox/+ – rtTA;Tet-ORUNX2) highly induced RUNX2 transgene expression was observed in the ovary [7]. A recent study confirmed the strong association of RUNX2 gene with ovulation, luteinization and steroidogenesis, since RUNX2 was down-regulated in gr.

Lease of antiviral agents to liver. J Pharm Pharmacol 2006, 58:321-326. 6. AmijiLease of antiviral

Lease of antiviral agents to liver. J Pharm Pharmacol 2006, 58:321-326. 6. Amiji
Lease of antiviral agents to liver. J Pharm Pharmacol 2006, 58:321-326. 6. Amiji MM, Vyas TK, Shah LK: Role of nanotechnology in HIV/AIDS treatment: potential to overcome the viral reservoir challenge. Discov Med 2006, 6:157-162. 7. Baert L, Schueller L, Tardy Y, Macbride D, Klooster GV, Borghys H, Cllessens E, Mooter GVD, Gysegem EV, Remoortee PV, Rosier PWJ: Development of an implantable infusion pump for sustained anti-HIV drug administration. Int J Pharm 2008, 355:38-44. 8. Tronchet JMJ, Seman M: Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase: from the biology of reverse transcription to molecular design. Current Topics in Medicinal Chemistry 2003, 3:1496-511. 9. Maga G, Ubiali D, Salvetti R, Pregnolato M, Spadari S: Selective interaction of the Human immunodeficiency virus type 1 reverse transcriptase non nucleoside inhibitor efavirenz and its thio-substituted analog with different enzyme-substrate complexes. Antimicrobial Agents and Chemotherapy 2000, 44:1186-1194.Ramana et al. Journal of Biomedical Science 2010, 17:57 http://www.jbiomedsci.com/content/17/1/Page 9 of10. Currier JS, Havlir DV: Complications of HIV Disease and Antiretroviral Therapy. Top HIV Med 2005, 13:16-23. 11. Chen R, Yokoyama M, Sato H, Reilly C, Mansky LM: Human immunodeficiency virus mutagenesis during antiviral therapy: impact of drug-resistant reverse transcriptase and nucleoside and non nucleoside reverse transcriptase inhibitors on human immunodeficiency virus type 1 mutation frequencies. J Virology 2005, 79:12045-12057. 12. Petit F, Fromenty B, Owen A, Estaquier J: Mitochondria are sensors for HIV drugs. Trends in PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27324125 Pharmacological Sciences 2005, 26:2558-2264. 13. Fiala M, Murphy T, MacDougall J, Yang W, Luque A: HAART drugs induce mitochondrial damage and intracellular gaps and gp120 causes apoptosis. J Cardiovascular Toxicology 2004, 4:327-337. 14. Kontorinis N, Dieterich D: Hepatotoxicity of Antiretroviral Therapy. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26100631 AIDS Rev 2003, 5:36-43. 15. Hofstede HJMT, Burger DM, Koopmans PP: Antiretroviral therapy in HIV patients: aspects of metabolic complications and mitochondrial toxicity. Netherlands J Medicine 2003, 61:393-403. 16. Pilon AA, Lum JJ, Dardon JS, Phenix BN, Douglas R, Badley AD: Induction of apoptosis by a nonnucleoside human immunodeficiency virus Type 1 reverse Transcriptase Inhibitor. Antimicrobial Agents and Chemotherapy 2002, 46:2687-2691. 17. Ferrari M: Nanovector therapeutics. Current opinion in chemical biology 2005, 9:343-346. 18. Duncan R: The drawing era of polymer therapeutics. Nature review drug discovery 2003, 3:347-360. 19. Gonzalez de Requena D, Nunez M, Jimenez Nacher I, Soriano V: Liver toxicity caused by nevirapine. AIDS Research Letters 2002, 16:290-291. 20. Betagiri GV, LLY-507 biological activity Deshmukh DV, Gupta RB: Oral sustained- release bioadhesive tablet formulation of didanosine. Drug Dev Ind Pharm 2001, 27:129-136. 21. Govender S, Pillay V, Chetty DJ, Essack SY, Dangor CM, Govender T: Optimisation and characterization of bioadhesive controlled release tetracycline microspheres. Int J Pharm 2005, 306:24-40. 22. Benghuzzi H: Long term sustained delivery of 3′-azido-2′,3′-dideoxy thymidine in vivo by means of HA and TCP delivery devices. Biomed Sci Instrum 2000, 36:343-348. 23. Desormeaux A, Bergeron MG: Liposome as drug delivery system: a strategic approach for the treatment of HIV infection. J Drug target 1998, 6:1-15. 24. Jin SX, Wang DZJ, Wang YZ, Hu HG, Deng YG: Pharmacokinetic and tissue distribution of zidovudine in rats followi.

Rting gates were set as depicted in Additional file 2: Figure SRting gates were set

Rting gates were set as depicted in Additional file 2: Figure S
Rting gates were set as depicted in Additional file 2: Figure S2 using the FMOs controls, as previously described [21,101]. The viability staining Vivid (Invitrogen) was included in each staining cocktail to exclude dead cells. The post-sort quality analysis indicated that sorted subsets were in average >99 pure based on CD3, CD4 and CD45RA expression (Additional file 1 and 2: Figure S1 2). Sorting based on CD25/CD127 expression led to a significant enrichment of naive T-cell subsets (>80 ), with the exception of CD25+CD127+ which were typically >50 enriched (Additional file 2: Figure S2).Th17 polarization in vitroNaive and memory T-cell subsets (106 cells/ml) sorted by FACS were stimulated with immobilized CD3 and soluble CD28 Abs (1 g/ml) and cultured in RPMI 1640 media supplemented with human recombinant IL-23 (50 ng/ml), TGF- (10 ng/ml), IL-1 (10 ng/ml), and IL-6 (50 ng/ml) cytokines and neutralizing IL-4 (1 g/ml) and IFN- Abs (10 g/ml) (R D Systems) for 12 days. Media including polarizing cytokines, Abs, and IL-2 (5 ng/ml) was refreshed at day 4 and 8 post-culture. Cells were split at day 4 and/or 8 post-culture for an optimal density ONO-4059 cancer 1-2×106 cells/well.Intracellular staining for flow cytometry analysisTotal or memory CD4+ T-cells were PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28494239 sorted from frozen PBMCs by negative selection using magnetic beads (Miltenyi). Cell purity (typically >95 ) was determined by FACS analysis upon staining with CD3-PB, CD4-Alexa700, and CD8-FITC Abs for total T-cell enrichment, together with CD45RA-APC eFluor780 and CCR7-PeCy7 Abs for memory T-cell enrichment. In some experiments (Figure 1),Cells were stimulated with PMA (50 ng/ml) and Ionomycin (1 g/ml) in the presence of Brefeldin A (2 g/ml) for 5 h or 17 h. The intracellular expression of IL-17A, IFN- and TNF- was quantified by flow cytometry (BD LSRII) upon staining with appropriate Abs using the Cytofix/Cytoperm kit (BD Biosciences) according to the manufacturer’s protocols. The intracellular expression of FoxP3 was quantified using the Anti-Human Foxp3 Staining Set Alexa Fluor?488 (eBioscience) according to the manufacturer’s protocol.ELISA quantification of IL-17A productionIL-17A levels in cell culture supernatants were quantified by a specific ELISA assay (eBiosciences) according to the manufacturer’s protocol.DaFonseca et al. Retrovirology (2015) 12:Page 20 ofQuantitative SYBR green real-time RT-PCRTotal RNA was isolated using RNeasy kit (Qiagen). The quality (260/280 ratio) and quantity of RNA collected were measured by a Pearl nanophotometer (Implen, Munich, Germany). One step SYBR Green real-time RTPCR (Qiagen) was carried out in a LightCycler 480 II (Roche) according to the manufacturer’s recommendations. The quantification of RORC mRNA relative to the 28S rRNA levels was performed as we previously described [21]. Each RT-PCR reaction was performed in triplicates.Real-time PCR quantification of Gag and integrated HIVDNAAdditional file 2: Figure S2. Flow cytometry sorting of phenotypically naive CD4+ T-cells with differential expression of CD25 and CD127. Total CD4+ T-cells were isolated from PBMCs by negative selection using magnetic beads (Miltenyi). Cells were PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29072704 stained with a cocktail of CD3, CD4, CD45RA, CCR7, CD25, and CD127 Abs and the viability dye Vivid. Viable (Vivid-) naive-like (CD45RA+CCR7+) CD4+ T-cells with a CD25+CD127- (nTregs), CD25-CD127+ (conventional nT), CD25+CD127+ (DP, double positive), and CD25-CD127- (DN, double negative) phenotype were sorted by flow cytometry.

B/dbpAB + Cef2 + aT dbpAB + Cef2 + aT wk 6 fpsyg.2015.00360 0/2 4/4 3/4 0/8 0/8 0/8 0/8 wk 9 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Ear 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Culture

B/dbpAB + Cef2 + aT dbpAB + Cef2 + aT wk 6 0/2 4/4 3/4 0/8 0/8 0/8 0/8 wk 9 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Ear 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Culture at 15 wk Bladder 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Joint 0/2 4/4 3/4 0/8 0/8 0/8 0/doi:10.1371/journal.pone.0121512.tPLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,8 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceFig 3. IgG antibody levels in mouse serum samples. Antibody levels were measured using enzyme immunoassays with whole B. burgdorferi lysate as antigen. In panel A, the XAV-939 chemical information results are from Experiment II, in panel B from Experiment IV, and in panels C and D combined from Experiments II and III. The results in each panel are obtained from an individual analysis. Each symbol represents the result of one animal. Results are expressed as OD492 values and all samples were analysed in duplicate. The line indicates the mean of each group. Groups with the same letter do not differ at 5 level of probability (Tukey’s HSD test, panels A and B). * P 0.05, *** P 0.001. doi:10.1371/journal.pone.0121512.gsusceptibility testing indicated that both strains were equally susceptible to ceftriaxone with MIC of 0.064 g/ml. B. burgdorferi cultures of ear biopsy samples taken at 6 and 9 weeks of infection were negative in dbpAB/dbpAB and dbpAB infected mice suggesting clearance of spirochetemia (Table 2, groups 9 and 10). In parallel, the post mortem B. burgdorferi cultures of ear, bladder and joint LDN193189MedChemExpress DM-3189 tissues did not show growth, and, importantly, there was no measurable swelling in the tibiotarsal joints of the treated animals (Fig. 2B, groups 9 and 10). Immunosuppression of the mice with anti-TNF-alpha treatment (once a week during weeks 7 to 10) did not have any effect on the culture results or on the arthritis development (Table 2 and Fig. 2B, groups 11 and 12).PLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,9 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTable 3. B. burgdorferi PCR results of Experiment II at 15 weeks of infection. flaB Group 6 7 8 9 10 11 12 Strain/treatment Uninfected dbpAB/dbpAB dbpAB dbpAB/dbpAB + Cef2 dbpAB + Cef2 dbpAB/dbpAB + Cef2 + aT dbpAB + Cef2 + aT Ear 0/2 3/4 0/4 0/8 0/8 0/8 0/8 Bladder 0/2 1/3a 0/4 0/8 0/8 0/8 0/8 Joint 0/2 4/4 2/4 5/8 0/8 8/8 0/8 Ear 0/2 2/4 1/4 0/8 0/8 0/8 0/8 ospA Bladder 0/2 4/4 0/4 0/8 0/8 0/8 0/8 Joint 0/2 4/4 3/4 8/8 0/8 8/8 0/a One sample not available for flaB PCR doi:10.1371/journal.pone.0121512.tFig 4. Bacterial load in joint samples. A 102 base pair fragment of ospA gene was amplified from the joint DNA samples. The minimal sensitivity of PCR was 40 bacterial cells. The results are expressed as the number of bacteria genomes per 100 ng of extracted DNA. Each symbol represents an individual animal and the samples were analysed in triplicate. In Experiment II, one joint sample of dbpAB infected mice was qPCR negative at 15 weeks of infection, in Experiment III jir.2010.0097 five joint samples of dbpAB infected animals were qPCR negative at two weeks, and in Experiment IV three joint samples of dbpAB infected and ceftriaxone treated (at six weeks of infection) mice were qPCR negative at 15 weeks. The line indicates the median of positive results in each group. “Cef” Ceftriaxone treatment, “aT” anti-TNF-alpha treatment. ** P 0.01 doi:10.1371/journal.pone.0121512.gPLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,10 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTaken together, the above results.B/dbpAB + Cef2 + aT dbpAB + Cef2 + aT wk 6 0/2 4/4 3/4 0/8 0/8 0/8 0/8 wk 9 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Ear 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Culture at 15 wk Bladder 0/2 4/4 3/4 0/8 0/8 0/8 0/8 Joint 0/2 4/4 3/4 0/8 0/8 0/8 0/doi:10.1371/journal.pone.0121512.tPLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,8 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceFig 3. IgG antibody levels in mouse serum samples. Antibody levels were measured using enzyme immunoassays with whole B. burgdorferi lysate as antigen. In panel A, the results are from Experiment II, in panel B from Experiment IV, and in panels C and D combined from Experiments II and III. The results in each panel are obtained from an individual analysis. Each symbol represents the result of one animal. Results are expressed as OD492 values and all samples were analysed in duplicate. The line indicates the mean of each group. Groups with the same letter do not differ at 5 level of probability (Tukey’s HSD test, panels A and B). * P 0.05, *** P 0.001. doi:10.1371/journal.pone.0121512.gsusceptibility testing indicated that both strains were equally susceptible to ceftriaxone with MIC of 0.064 g/ml. B. burgdorferi cultures of ear biopsy samples taken at 6 and 9 weeks of infection were negative in dbpAB/dbpAB and dbpAB infected mice suggesting clearance of spirochetemia (Table 2, groups 9 and 10). In parallel, the post mortem B. burgdorferi cultures of ear, bladder and joint tissues did not show growth, and, importantly, there was no measurable swelling in the tibiotarsal joints of the treated animals (Fig. 2B, groups 9 and 10). Immunosuppression of the mice with anti-TNF-alpha treatment (once a week during weeks 7 to 10) did not have any effect on the culture results or on the arthritis development (Table 2 and Fig. 2B, groups 11 and 12).PLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,9 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTable 3. B. burgdorferi PCR results of Experiment II at 15 weeks of infection. flaB Group 6 7 8 9 10 11 12 Strain/treatment Uninfected dbpAB/dbpAB dbpAB dbpAB/dbpAB + Cef2 dbpAB + Cef2 dbpAB/dbpAB + Cef2 + aT dbpAB + Cef2 + aT Ear 0/2 3/4 0/4 0/8 0/8 0/8 0/8 Bladder 0/2 1/3a 0/4 0/8 0/8 0/8 0/8 Joint 0/2 4/4 2/4 5/8 0/8 8/8 0/8 Ear 0/2 2/4 1/4 0/8 0/8 0/8 0/8 ospA Bladder 0/2 4/4 0/4 0/8 0/8 0/8 0/8 Joint 0/2 4/4 3/4 8/8 0/8 8/8 0/a One sample not available for flaB PCR doi:10.1371/journal.pone.0121512.tFig 4. Bacterial load in joint samples. A 102 base pair fragment of ospA gene was amplified from the joint DNA samples. The minimal sensitivity of PCR was 40 bacterial cells. The results are expressed as the number of bacteria genomes per 100 ng of extracted DNA. Each symbol represents an individual animal and the samples were analysed in triplicate. In Experiment II, one joint sample of dbpAB infected mice was qPCR negative at 15 weeks of infection, in Experiment III jir.2010.0097 five joint samples of dbpAB infected animals were qPCR negative at two weeks, and in Experiment IV three joint samples of dbpAB infected and ceftriaxone treated (at six weeks of infection) mice were qPCR negative at 15 weeks. The line indicates the median of positive results in each group. “Cef” Ceftriaxone treatment, “aT” anti-TNF-alpha treatment. ** P 0.01 doi:10.1371/journal.pone.0121512.gPLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,10 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTaken together, the above results.

Racy. It is best to use plain language for these messages

Racy. It is best to use plain language for these messages so that community members can easily understand them. Messages should: ?Be simple, clear, and direct; ?Use the fewest words needed to convey jasp.12117 key information; ?Communicate one to three key points at most; ?Be free of jargon and aimed at approximately a sixth-grade reading level (guidelines on simplifying messages can be found in the U.S. government’s Plain Language Action and Information Network Quick Reference Guide12 and the Clear Communication Index);13 ?Be translated in appropriate languages for communities; and?Be framed in positive terms (i.e., focused on what to do as opposed to what not to do). Step 8: use a variety of methods to convey and amplify messages Health department communications and community mobilization teams may find it useful to disseminate health messages through existing, established networks (e.g., ethnic media outlets) rather than trying to create new channels. Working through existing networks may better meet partners’ needs and help to ensure overall message sustainability. CFBOs can provide important insight into these established networks. For effective communications, health officials should consider engaging at multiple levels. Low-level engagement uses channels such as traditional advertisements, websites, flyers, and press releases. Medium-level engagement uses a mix of indirect and semidirect communication pathways (e.g., prerecorded, widely distributed phone messages). High-level engagement relies on face-to-face, direct communication.14 Trusted messengers are vital in conveying informationFigure 2. Resources for health GDC-0084 manufacturer communicators on how to work with community and faith-based organizations to prepare for an Ebola response and other public health emergenciesResourceHHS Center for FaithBased and Neighborhood Partnerships website CDC’s Crisis and Emergency Risk Communication ProgramTools offeredContains tool kits and resources to help community organizations work with health departments. Tools are available to assist faith leaders in Mdivi-1 price helping communities address Ebola concerns. (http://www.hhs.gov/partnerships/resources/index.html) Tools that can help health department communicators involve partner organizations, including resources on working with communities and building consensus during a public health crisis. (http://emergency.cdc.gov/cerc/resources/pdf/cerc_2014edition.pdf) A free online course that provides risk communication techniques to j.jebo.2013.04.005 help partners communicate accurate risk information during times of anxiety and fear. (http://emergency.cdc.gov/cerc/training/basic/index.asp)CDC Clear Communication Index CDC ASTHO At-Risk Populations Guidance National Voluntary Organizations Active in Disaster website Model Practices to Increase Influenza Prevention Among Hard-to-Reach PopulationsProvides a research-based tool to help users develop and assess public communication materials. (http://www.cdc.gov/ccindex/index.html) Provides a framework and recommendations to assist planning for at-risk populations during pandemics and other public health emergencies. (http://www.astho.org/programs/infectious-disease/at-risk-populations) A nonpartisan, nonprofit, membership-based organization that has resources for organizations wishing to share knowledge and resources in disasters. (www.nvoad.org) A guide developed by ASTHO in collaboration with Emory University’s Interfaith Health Program, designed for public health and religious leaders. It aims to str.Racy. It is best to use plain language for these messages so that community members can easily understand them. Messages should: ?Be simple, clear, and direct; ?Use the fewest words needed to convey jasp.12117 key information; ?Communicate one to three key points at most; ?Be free of jargon and aimed at approximately a sixth-grade reading level (guidelines on simplifying messages can be found in the U.S. government’s Plain Language Action and Information Network Quick Reference Guide12 and the Clear Communication Index);13 ?Be translated in appropriate languages for communities; and?Be framed in positive terms (i.e., focused on what to do as opposed to what not to do). Step 8: use a variety of methods to convey and amplify messages Health department communications and community mobilization teams may find it useful to disseminate health messages through existing, established networks (e.g., ethnic media outlets) rather than trying to create new channels. Working through existing networks may better meet partners’ needs and help to ensure overall message sustainability. CFBOs can provide important insight into these established networks. For effective communications, health officials should consider engaging at multiple levels. Low-level engagement uses channels such as traditional advertisements, websites, flyers, and press releases. Medium-level engagement uses a mix of indirect and semidirect communication pathways (e.g., prerecorded, widely distributed phone messages). High-level engagement relies on face-to-face, direct communication.14 Trusted messengers are vital in conveying informationFigure 2. Resources for health communicators on how to work with community and faith-based organizations to prepare for an Ebola response and other public health emergenciesResourceHHS Center for FaithBased and Neighborhood Partnerships website CDC’s Crisis and Emergency Risk Communication ProgramTools offeredContains tool kits and resources to help community organizations work with health departments. Tools are available to assist faith leaders in helping communities address Ebola concerns. (http://www.hhs.gov/partnerships/resources/index.html) Tools that can help health department communicators involve partner organizations, including resources on working with communities and building consensus during a public health crisis. (http://emergency.cdc.gov/cerc/resources/pdf/cerc_2014edition.pdf) A free online course that provides risk communication techniques to j.jebo.2013.04.005 help partners communicate accurate risk information during times of anxiety and fear. (http://emergency.cdc.gov/cerc/training/basic/index.asp)CDC Clear Communication Index CDC ASTHO At-Risk Populations Guidance National Voluntary Organizations Active in Disaster website Model Practices to Increase Influenza Prevention Among Hard-to-Reach PopulationsProvides a research-based tool to help users develop and assess public communication materials. (http://www.cdc.gov/ccindex/index.html) Provides a framework and recommendations to assist planning for at-risk populations during pandemics and other public health emergencies. (http://www.astho.org/programs/infectious-disease/at-risk-populations) A nonpartisan, nonprofit, membership-based organization that has resources for organizations wishing to share knowledge and resources in disasters. (www.nvoad.org) A guide developed by ASTHO in collaboration with Emory University’s Interfaith Health Program, designed for public health and religious leaders. It aims to str.

Lch t-tests. We conducted the same procedure to analyse patterns of

Lch t-tests. We conducted the same procedure to analyse patterns of phylogenetic diversity (PD) and its respective changes from wet to dry season. Our analyses are based on a time-calibrated phylogeny of mantellid species [50] as all tadpoles sampled in the streams belonged to this family [40]. We pruned from this tree all taxa not represented in our Ranomafana Win 63843 msds tadpole sampling using TreeEdit version v1.0a10. This reduced the number of species by retaining branch lengths. For a few so far undescribed species, genetic data were insufficient to include them in the tree. In these cases, other species that are known to be in the same clade (according to molecular data of Vieites et al. [34]) were used as replacement for the purpose of PD calculation. Similar to FD calculations [43, 44, 51], we extracted branch lengths from the tree for the assemblages [52] by using the function treedive included in the R package vegan. The sum of branch lengths needed to connect all species of an assemblage represents the assemblage’s PD. All analyses were run using the statistical software R 2.15.1 [53]. Packages used for FD calculations include car R package version 2.0?8 [54], gtools R package version 2.7.0. [55], cluster R package version 1.14.2 [56] and clue R package version 0.3?5 [57, 58]. For PD calculations we used the R packages ape version 3.0? [59, 60] and vegan version 2.0? [61]. Moran’s I was also calculated using the package ape.ResultsSummarizing data over wet and dry seasons, we found tadpoles of a total of 31 species in all twelve stream sections (= assemblages). In the wet season we found five to 15 species, in the dry season two to twelve species per assemblage. Mean SR in the dry season was about 27 lower than in the wet season (paired t-test, scan/nsw074 t = 3.44, df = 11, p = 0.006). Beside this decrease inPLOS ONE | DOI:10.1371/journal.pone.0151744 March 25,6 /Seasons Affect Functional and Phylogenetic DiversityFig 3. Change from the wet to the dry season: Deviation of observed loss of FD and PD from the null models. The dashed lines represent the null models for the change from the wet to the dry season, the box-whisker-plots show the observed deviations from the null models. Values below the dashed line show a smaller loss, values above the line show a higher loss of FD and PD than PG-1016548 chemical information predicted by the null models. jir.2012.0140 FD of tadpoles decreases significantly less than predicted whereas PD decreases significantly more than predicted. doi:10.1371/journal.pone.0151744.gSR (i.e., probably due to reduced reproductive activity), a species turnover from wet to dry season was observed in eight streams, i.e., an assemblage in the dry season harboured on average one or more species that were not present in the assemblage of the same stream during the wet season. However, no species was exclusively found in the dry season.Functional diversityAs observed for SR, FD decreased from the wet to the dry season. However, the observed relative loss of FD (8 ) differs from the loss predicted by the null models (17 ) based on the observed loss in SR (paired t-test, t = -2.34, df = 11, p = 0.04; Fig 3). This difference suggestsPLOS ONE | DOI:10.1371/journal.pone.0151744 March 25,7 /Seasons Affect Functional and Phylogenetic DiversityFig 4. Comparing null models and observed FD from tadpole assemblages from RNP. Given are observed (dark grey filled circles, continuous regression line) and null model FD (light grey circles with dark margins, dashed line) along the observed S.Lch t-tests. We conducted the same procedure to analyse patterns of phylogenetic diversity (PD) and its respective changes from wet to dry season. Our analyses are based on a time-calibrated phylogeny of mantellid species [50] as all tadpoles sampled in the streams belonged to this family [40]. We pruned from this tree all taxa not represented in our Ranomafana tadpole sampling using TreeEdit version v1.0a10. This reduced the number of species by retaining branch lengths. For a few so far undescribed species, genetic data were insufficient to include them in the tree. In these cases, other species that are known to be in the same clade (according to molecular data of Vieites et al. [34]) were used as replacement for the purpose of PD calculation. Similar to FD calculations [43, 44, 51], we extracted branch lengths from the tree for the assemblages [52] by using the function treedive included in the R package vegan. The sum of branch lengths needed to connect all species of an assemblage represents the assemblage’s PD. All analyses were run using the statistical software R 2.15.1 [53]. Packages used for FD calculations include car R package version 2.0?8 [54], gtools R package version 2.7.0. [55], cluster R package version 1.14.2 [56] and clue R package version 0.3?5 [57, 58]. For PD calculations we used the R packages ape version 3.0? [59, 60] and vegan version 2.0? [61]. Moran’s I was also calculated using the package ape.ResultsSummarizing data over wet and dry seasons, we found tadpoles of a total of 31 species in all twelve stream sections (= assemblages). In the wet season we found five to 15 species, in the dry season two to twelve species per assemblage. Mean SR in the dry season was about 27 lower than in the wet season (paired t-test, scan/nsw074 t = 3.44, df = 11, p = 0.006). Beside this decrease inPLOS ONE | DOI:10.1371/journal.pone.0151744 March 25,6 /Seasons Affect Functional and Phylogenetic DiversityFig 3. Change from the wet to the dry season: Deviation of observed loss of FD and PD from the null models. The dashed lines represent the null models for the change from the wet to the dry season, the box-whisker-plots show the observed deviations from the null models. Values below the dashed line show a smaller loss, values above the line show a higher loss of FD and PD than predicted by the null models. jir.2012.0140 FD of tadpoles decreases significantly less than predicted whereas PD decreases significantly more than predicted. doi:10.1371/journal.pone.0151744.gSR (i.e., probably due to reduced reproductive activity), a species turnover from wet to dry season was observed in eight streams, i.e., an assemblage in the dry season harboured on average one or more species that were not present in the assemblage of the same stream during the wet season. However, no species was exclusively found in the dry season.Functional diversityAs observed for SR, FD decreased from the wet to the dry season. However, the observed relative loss of FD (8 ) differs from the loss predicted by the null models (17 ) based on the observed loss in SR (paired t-test, t = -2.34, df = 11, p = 0.04; Fig 3). This difference suggestsPLOS ONE | DOI:10.1371/journal.pone.0151744 March 25,7 /Seasons Affect Functional and Phylogenetic DiversityFig 4. Comparing null models and observed FD from tadpole assemblages from RNP. Given are observed (dark grey filled circles, continuous regression line) and null model FD (light grey circles with dark margins, dashed line) along the observed S.

Side” being involved in the pathogenesis of diseases (fibrosis, inflammation, and

Side” being involved in the NSC 697286 web pathogenesis of diseases (fibrosis, inflammation, and cancer, among many others); at the cellular level, it modulates migration, chemotaxis, proliferation, survival, and other processes (see [1?] and references therein). LPA actions are mainly exerted through a family of G protein-coupled receptors (GPCRs), that is, the LPA receptors, comprising six members that are currently designated LPA1?; the possibility that GPR87 could be also a member of this family has been suggested, i. e., such as LPA7 [1?]. Of jasp.12117 these receptors, LPA1, LPA2 and LPA3 are phylogenetically related among themselves and also with those of other bioactive lipids (the endothelial differentiation gene [“edg”] family); the remaining LPA receptors are distant phylogenetically from these and are more closely related with the purinergic receptor family [1?]. Evolutionary aspects of these receptors, among vertebrates, have been recently reported [7]. It is also known that LPA can modulate transcription through nuclear receptors, such as the peroxisome proliferator-activated receptor [8]. LPA also activates the TRPV1 ion channel involved in the control of body temperature and nociception [9]. Our present work deals exclusively with the LPA1? receptors. The actions of these receptors have been studied using many different natural (i. e. endogenously expressed) and transfected cellular and systemic models. However, few studies have analyzed LPA1? desensitization and internalization employing the same cellular model. In particular, the phosphorylation of these receptors has been scarcely studied. To the best of our knowledge, solely LPA1 receptor phosphorylation has been reported and only by our own group [4, 10?4]. The present work was designed to fulfill this gap in knowledge. Desensitization, defined as a stage of reduced BL-8040 price sensitivity to a particular stimulus, can involve a large number of processes with different time scales. It is generally accepted that GPCR sensitivity (desensitization/ resensitization) involves phosphorylation/ dephosphorylation cycles controlled by particular protein kinases and phosphatases wcs.1183 [15?0]; although there is evidence also for phosphorylation-independent desensitization [21]. The majority of current data indicate that agonist-induced receptor desensitization (homologous desensitization) involves receptor phosphorylation by G protein-coupled receptor kinases (GRKs) whereas desensitization of unoccupied receptors, i. e. agonist-independent (heterologous desensitization) mainly involves signaling activated kinases such as the second messenger-activated kinases, protein kinase A and protein kinase C (PKC), among others [15?0]. Receptor internalization appears to be related with receptor phosphorylation. Current ideas indicate that phosphorylated receptors interact with -arrestins and act as molecular bridges with clathrin, clustering receptors that internalize in coated vesicles; such internalization can lead receptors to plasma membrane recycling, trafficking to other compartments or to degradation. Variation in the phosphorylation pattern of a given receptor has been observed and it has been suggested that such phosphorylation “bar code” might determine receptor’s destination and function [19, 22, 23]. Recently, we reported differential association of 1B-adrenergic receptors to Rab proteins during internalizations induced by agonists (homologous) or unrelated (heterologous) stimuli [24]. In silico analysis showed that.Side” being involved in the pathogenesis of diseases (fibrosis, inflammation, and cancer, among many others); at the cellular level, it modulates migration, chemotaxis, proliferation, survival, and other processes (see [1?] and references therein). LPA actions are mainly exerted through a family of G protein-coupled receptors (GPCRs), that is, the LPA receptors, comprising six members that are currently designated LPA1?; the possibility that GPR87 could be also a member of this family has been suggested, i. e., such as LPA7 [1?]. Of jasp.12117 these receptors, LPA1, LPA2 and LPA3 are phylogenetically related among themselves and also with those of other bioactive lipids (the endothelial differentiation gene [“edg”] family); the remaining LPA receptors are distant phylogenetically from these and are more closely related with the purinergic receptor family [1?]. Evolutionary aspects of these receptors, among vertebrates, have been recently reported [7]. It is also known that LPA can modulate transcription through nuclear receptors, such as the peroxisome proliferator-activated receptor [8]. LPA also activates the TRPV1 ion channel involved in the control of body temperature and nociception [9]. Our present work deals exclusively with the LPA1? receptors. The actions of these receptors have been studied using many different natural (i. e. endogenously expressed) and transfected cellular and systemic models. However, few studies have analyzed LPA1? desensitization and internalization employing the same cellular model. In particular, the phosphorylation of these receptors has been scarcely studied. To the best of our knowledge, solely LPA1 receptor phosphorylation has been reported and only by our own group [4, 10?4]. The present work was designed to fulfill this gap in knowledge. Desensitization, defined as a stage of reduced sensitivity to a particular stimulus, can involve a large number of processes with different time scales. It is generally accepted that GPCR sensitivity (desensitization/ resensitization) involves phosphorylation/ dephosphorylation cycles controlled by particular protein kinases and phosphatases wcs.1183 [15?0]; although there is evidence also for phosphorylation-independent desensitization [21]. The majority of current data indicate that agonist-induced receptor desensitization (homologous desensitization) involves receptor phosphorylation by G protein-coupled receptor kinases (GRKs) whereas desensitization of unoccupied receptors, i. e. agonist-independent (heterologous desensitization) mainly involves signaling activated kinases such as the second messenger-activated kinases, protein kinase A and protein kinase C (PKC), among others [15?0]. Receptor internalization appears to be related with receptor phosphorylation. Current ideas indicate that phosphorylated receptors interact with -arrestins and act as molecular bridges with clathrin, clustering receptors that internalize in coated vesicles; such internalization can lead receptors to plasma membrane recycling, trafficking to other compartments or to degradation. Variation in the phosphorylation pattern of a given receptor has been observed and it has been suggested that such phosphorylation “bar code” might determine receptor’s destination and function [19, 22, 23]. Recently, we reported differential association of 1B-adrenergic receptors to Rab proteins during internalizations induced by agonists (homologous) or unrelated (heterologous) stimuli [24]. In silico analysis showed that.

Normal: BMI< = 23.9, overweight: 24 = = 27) was used to classify BMI.

Normal: BMI< = 23.9, overweight: 24 = = 27) was used to classify BMI. Overweight and obesity were classified together into a group in the analysis. The EPQ-REC original score was transformed into a T score according to Chinese norms, and then categorized into three groups (<43.3, 43.3?6.7 and >56.7). Job burnout total score was also categorized into three groups(<50, 50?75 and !75). The outcome variable considered in the model was categorized as a dichotomous variable (injury or no-injury). To access the relationships GW9662 web between various factors with injury, the crude odds ratios (OR) and their 95 confidence intervals (CI) were calculated with univariate logistic regression. The adjusted odds ratios (ORa) were then estimated using multivariable logistic regression with stepwise procedure. All these statistical analysis were conducted using SAS version 9.3 (SAS Institute, Inc., Cary, NC, USA), and a level of 0.05 was used to declare statistical significance.ResultsA total number of 3618 effective respondents were got from the 4319 participants who had been recruited (83.77 ). The mean age of coal miners was 41.5 years with standard deviation 8.65. The median time that passed between each participant’s last injury and their interview was 1.54 years. Table 1 shows that there were 137 reported accidents among the 3618 coal workers (3.79 ) who experienced at least one accident. The total number of injuries was 138: with one accident n = 136 (3.76 ); with two accidents n = 1 (0.03 ). Table 2 presents the distribution of injuries according to workplace, type of injury, localization of injury and severity of injury. For all injuries, underground represented about 79.71 , and above ground about 20.29 . Smashing injury was the most common pnas.1408988111 injury accounting for 53.63 , sprains and luxation 23.92 . The localization of injury happened mainly in limbs (57.25 ), followed by head and face (18.12 ) and trunk (17.39 ). The majority of injuries (60.87 ) were minor injury. Table 3 indicates that workplace dangerousness had significant differences in different age groups. Workers aged 55 or more tended to rate their workplace as never dangerous, more often than younger workers. Significant differences also existed between males and females.Table 1. Distribution of wcs.1183 the nonfatal occupational injures ( ). The number of injuries 0 1 2 Total doi:10.1371/journal.pone.0134367.t001 Frequencies (n) 3481 136 1 3618 Proportion ( ) 96.21 3.76 0.03 100.0 3.76 0.03 Prevalence ( )PLOS ONE | DOI:10.1371/journal.pone.0134367 July 31,5 /The Risk Factors of Nonfatal Occupational Injury in the Coal WorkersTable 2. Characteristic distribution of nonfatal occupational injuries. Variable Type of injury Characteristics smashing injury blast injury mechanical traffic injury falling injury sprains and luxation poisoning others Localization of injury head and face trunk limbs whole body others Severity of injury minor moderate serious doi:10.1371/journal.pone.0134367.t002 Table 3. The Aviptadil structure danger of the work environment in different groups. The danger of the work environment ( ) Never Age 25yr 25 35yr 35 45yr 45 55yr !55yr Gender male female doi:10.1371/journal.pone.0134367.t003 24.72 26.65 27.50 29.37 40.25 20.90 68.79 Seldom 19.10 15.53 17.58 17.78 20.34 17.58 16.03 Sometimes 26.97 24.70 25.09 25.70 20.76 27.98 8.97 Often 13.48 14.13 11.12 11.50 10.17 13.53 3.97 Usually 15.73 18.99 18.71 15.65 8.47 20.01 2.24 <0.001 0.008 P n 74 5 9 5 33 3 9 25 24 79 3 7 84 50 4.Normal: BMI< = 23.9, overweight: 24 = = 27) was used to classify BMI. Overweight and obesity were classified together into a group in the analysis. The EPQ-REC original score was transformed into a T score according to Chinese norms, and then categorized into three groups (<43.3, 43.3?6.7 and >56.7). Job burnout total score was also categorized into three groups(<50, 50?75 and !75). The outcome variable considered in the model was categorized as a dichotomous variable (injury or no-injury). To access the relationships between various factors with injury, the crude odds ratios (OR) and their 95 confidence intervals (CI) were calculated with univariate logistic regression. The adjusted odds ratios (ORa) were then estimated using multivariable logistic regression with stepwise procedure. All these statistical analysis were conducted using SAS version 9.3 (SAS Institute, Inc., Cary, NC, USA), and a level of 0.05 was used to declare statistical significance.ResultsA total number of 3618 effective respondents were got from the 4319 participants who had been recruited (83.77 ). The mean age of coal miners was 41.5 years with standard deviation 8.65. The median time that passed between each participant's last injury and their interview was 1.54 years. Table 1 shows that there were 137 reported accidents among the 3618 coal workers (3.79 ) who experienced at least one accident. The total number of injuries was 138: with one accident n = 136 (3.76 ); with two accidents n = 1 (0.03 ). Table 2 presents the distribution of injuries according to workplace, type of injury, localization of injury and severity of injury. For all injuries, underground represented about 79.71 , and above ground about 20.29 . Smashing injury was the most common pnas.1408988111 injury accounting for 53.63 , sprains and luxation 23.92 . The localization of injury happened mainly in limbs (57.25 ), followed by head and face (18.12 ) and trunk (17.39 ). The majority of injuries (60.87 ) were minor injury. Table 3 indicates that workplace dangerousness had significant differences in different age groups. Workers aged 55 or more tended to rate their workplace as never dangerous, more often than younger workers. Significant differences also existed between males and females.Table 1. Distribution of wcs.1183 the nonfatal occupational injures ( ). The number of injuries 0 1 2 Total doi:10.1371/journal.pone.0134367.t001 Frequencies (n) 3481 136 1 3618 Proportion ( ) 96.21 3.76 0.03 100.0 3.76 0.03 Prevalence ( )PLOS ONE | DOI:10.1371/journal.pone.0134367 July 31,5 /The Risk Factors of Nonfatal Occupational Injury in the Coal WorkersTable 2. Characteristic distribution of nonfatal occupational injuries. Variable Type of injury Characteristics smashing injury blast injury mechanical traffic injury falling injury sprains and luxation poisoning others Localization of injury head and face trunk limbs whole body others Severity of injury minor moderate serious doi:10.1371/journal.pone.0134367.t002 Table 3. The danger of the work environment in different groups. The danger of the work environment ( ) Never Age 25yr 25 35yr 35 45yr 45 55yr !55yr Gender male female doi:10.1371/journal.pone.0134367.t003 24.72 26.65 27.50 29.37 40.25 20.90 68.79 Seldom 19.10 15.53 17.58 17.78 20.34 17.58 16.03 Sometimes 26.97 24.70 25.09 25.70 20.76 27.98 8.97 Often 13.48 14.13 11.12 11.50 10.17 13.53 3.97 Usually 15.73 18.99 18.71 15.65 8.47 20.01 2.24 <0.001 0.008 P n 74 5 9 5 33 3 9 25 24 79 3 7 84 50 4.

T-tests [52] at P-value = 0.1, rejecting the null ^ ^ hypothesis H0 that x are

T-tests [52] at P-value = 0.1, rejecting the null ^ ^ hypothesis H0 that x are consistent across the databases, H0 : x ?0. Thus, x ij express the consistency of the database i with the other databases, along the j-th network measure. Note also that the absolute values of individual residuals j^j imply a ranking R over the databases, where x the database with the lowest j^j has rank one, the second one has rank two and the one with x the largest j^j has rank N. x T0901317MedChemExpress T0901317 Identifying independent network measures. Denote rij to be the Pearson product-moment ^ correlation coefficient of the residuals x for i-th and j-th network measure over all databases. Spearman rank correlation coefficient ij is defined as the Pearson coefficient of the ranks R for i-th and j-th statistics. Under the null hypothesis of statistical independence of i-th and j-th statistics, H0:ij = 0, adjusted Fisher transformation [53]: pffiffiffiffiffiffiffiffiffiffiffiffi N ?3 1 ?rij ln 2 1 ?rij ??PLOS ONE | DOI:10.1371/journal.pone.0127390 May 18,12 /Consistency of Databasesapproximately follows a standard normal distribution. Pairwise independence of the selected network measures is thus confirmed by the independent two-tailed z-tests. This gives 13 independent measures for directed, and 7 independent measures for undirected networks, as shown in the Fig 3. Furthermore, Friedman rank test [54] confirms that chosen set of measures exhibits significant internal differences, as to still be informative on the databases (see below). Ranking of databases. Significant inconsistencies between the databases are exposed using the methodology introduced for comparing classification algorithms over multiple data sets [55]. Denote Ri to be the mean rank of i-th database over the fnins.2015.00094 selected measure, Ri = j Rij/K, where K is the number of independent measures K 2 7, 13. One-tailed Friedman rank test [54, 56] first verifies the null hypothesis that the databases are statistically equivalent and thus their ranks Ri should equal, H0:Ri = Rj. Under the assumption that the selected statistics are indeed independent, the Friedman testing statistic [54]: ! 2 X 12K N ?1?2 ??Ri ?4 N ?1?i has 2-distribution with N-1 degrees of freedom. By rejecting the hypothesis at P-value = 0.1, we proceed with the Nemenyi post-hoc test that reveals wcs.1183 databases whose ranks Ri differ more than the critical difference [57]: rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi N ?1???; q 6K where q is the critical value based on the studentized range statistic [55], q = 2.59 at Pvalue = 0.1. A critical difference diagram plots the databases with no statistically significant inconsistencies in the selected statistics [55].Supporting InformationS1 File. Degree and clustering graphical profiles, continuation of network measures. Node degree and clustering profiles and distributions of all the considered networks, along with other network statistics. See Methods for interpretation and details on computation. (PDF)AcknowledgmentsAuthors thank American Physical Society and Thomson Reuters for providing the data. Thomson Reuters had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Work supported by purchase Naramycin A Creative Core FISNM-3330-13-500033 funded by the European Union and The European Regional Development Fund, by the H2020-MSCA-ITN-2015 project COSMOS 642563, by the Slovenian Research Agency (ARRS) via programs P2-0359, P1-0383, via projects J1-5454, L7-4119,.T-tests [52] at P-value = 0.1, rejecting the null ^ ^ hypothesis H0 that x are consistent across the databases, H0 : x ?0. Thus, x ij express the consistency of the database i with the other databases, along the j-th network measure. Note also that the absolute values of individual residuals j^j imply a ranking R over the databases, where x the database with the lowest j^j has rank one, the second one has rank two and the one with x the largest j^j has rank N. x Identifying independent network measures. Denote rij to be the Pearson product-moment ^ correlation coefficient of the residuals x for i-th and j-th network measure over all databases. Spearman rank correlation coefficient ij is defined as the Pearson coefficient of the ranks R for i-th and j-th statistics. Under the null hypothesis of statistical independence of i-th and j-th statistics, H0:ij = 0, adjusted Fisher transformation [53]: pffiffiffiffiffiffiffiffiffiffiffiffi N ?3 1 ?rij ln 2 1 ?rij ??PLOS ONE | DOI:10.1371/journal.pone.0127390 May 18,12 /Consistency of Databasesapproximately follows a standard normal distribution. Pairwise independence of the selected network measures is thus confirmed by the independent two-tailed z-tests. This gives 13 independent measures for directed, and 7 independent measures for undirected networks, as shown in the Fig 3. Furthermore, Friedman rank test [54] confirms that chosen set of measures exhibits significant internal differences, as to still be informative on the databases (see below). Ranking of databases. Significant inconsistencies between the databases are exposed using the methodology introduced for comparing classification algorithms over multiple data sets [55]. Denote Ri to be the mean rank of i-th database over the fnins.2015.00094 selected measure, Ri = j Rij/K, where K is the number of independent measures K 2 7, 13. One-tailed Friedman rank test [54, 56] first verifies the null hypothesis that the databases are statistically equivalent and thus their ranks Ri should equal, H0:Ri = Rj. Under the assumption that the selected statistics are indeed independent, the Friedman testing statistic [54]: ! 2 X 12K N ?1?2 ??Ri ?4 N ?1?i has 2-distribution with N-1 degrees of freedom. By rejecting the hypothesis at P-value = 0.1, we proceed with the Nemenyi post-hoc test that reveals wcs.1183 databases whose ranks Ri differ more than the critical difference [57]: rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi N ?1???; q 6K where q is the critical value based on the studentized range statistic [55], q = 2.59 at Pvalue = 0.1. A critical difference diagram plots the databases with no statistically significant inconsistencies in the selected statistics [55].Supporting InformationS1 File. Degree and clustering graphical profiles, continuation of network measures. Node degree and clustering profiles and distributions of all the considered networks, along with other network statistics. See Methods for interpretation and details on computation. (PDF)AcknowledgmentsAuthors thank American Physical Society and Thomson Reuters for providing the data. Thomson Reuters had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Work supported by Creative Core FISNM-3330-13-500033 funded by the European Union and The European Regional Development Fund, by the H2020-MSCA-ITN-2015 project COSMOS 642563, by the Slovenian Research Agency (ARRS) via programs P2-0359, P1-0383, via projects J1-5454, L7-4119,.

R Valley Survey [10, 83]. Here, the assemblages have been standardized in terms

R Valley Survey [10, 83]. Here, the Varlitinib dose assemblages have been standardized in terms of type descriptions and are all of sufficient sample sizes. The error bars indicate the 99 confidence interval for the type frequencies. The largest seriation solutions formed eight spatial sets. The assemblage from Parkin (11-N-1) falls into two SCR7 site different sets, suggesting that it served as a central node of interaction between communities. The Holden Lake assemblage appears as a valid addition to all solutions, supporting the idea that it is earlier than the other samples in the analysis. doi:10.1371/journal.pone.0124942.gUsing a subset of data from the LMV assemblages and new ceramic collections from seven deposits in northeastern Arkansas [32, 83] and shown in Table 2, Lipo used seriation-based techniques and simulations of cultural transmission to account for patterns of stylistic similarity in varying spatial and temporal configurations among 20 late prehistoric locations. Through his analysis, Lipo [80, 83] demonstrated that data generated from the original collections are well suited for examining transmission. In his analysis, Lipo [80, 83] constructed deterministic seriations for the assemblages using a manual graphical technique and found that no single solution could be obtained using the 20 assemblages. Instead, fpsyg.2016.01503 the set of assemblages had to divided into 8 different spatial groups (Figs 9 and 10). These groups reflected the effects of local transmission among communities that overwhelms the effects of longer-range interaction within the region. Interestingly, two valid seriation solutions in the “Parkin” area (Groups 2 and 3 in Fig 10) overlap with one another in that they both share the assemblage 11-N-1, the Parkin site. Lipo [83] explained this result asPLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,19 /The IDSS Frequency Seriation AlgorithmFig 10. Spatial distribution of seriation groups with St. Francis and Memphis Assemblages consisting of Lipo [84] and Phillips et al. [10] samples. Labels for groups refer to seriation solutions numbered in Fig 9. While each seriation group also includes Holden Lake, this assemblage is removed here for visual clarity. The groups are strongly spatial in their configuration. Interestingly, the Parkin (11-N-1) assemblage falls into groups 2 and 3 suggesting that it served as a central node, possibly indicating emerging social complexity. doi:10.1371/journal.pone.0124942.gPLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,20 /The IDSS Frequency Seriation Algorithmthe effect of Parkin acting as a central “node” in a network and possibly indicative of emerging social complexity among otherwise functionally redundant settlements. While Lipo’s result demonstrates the potential for seriation as a means of explaining patterns of cultural transmission, the results and the approach as a whole are limited in practical utility for several reasons. First, the seriation results jir.2010.0097 were created by hand sorting following graphic methods outlined by Ford [6, 10] though assisted using spreadsheet macros in Microsoft Excel [83]. Consequently, we have no way of knowing whether the final sets of orders are the largest set or whether all possible solutions are represented. Second, while Lipo created confidence intervals for each class frequency and tested the pairwise ordering of assemblages, the inability to assess the chosen solution with respect to the entire search space limits confidence in the results. Finally, the us.R Valley Survey [10, 83]. Here, the assemblages have been standardized in terms of type descriptions and are all of sufficient sample sizes. The error bars indicate the 99 confidence interval for the type frequencies. The largest seriation solutions formed eight spatial sets. The assemblage from Parkin (11-N-1) falls into two different sets, suggesting that it served as a central node of interaction between communities. The Holden Lake assemblage appears as a valid addition to all solutions, supporting the idea that it is earlier than the other samples in the analysis. doi:10.1371/journal.pone.0124942.gUsing a subset of data from the LMV assemblages and new ceramic collections from seven deposits in northeastern Arkansas [32, 83] and shown in Table 2, Lipo used seriation-based techniques and simulations of cultural transmission to account for patterns of stylistic similarity in varying spatial and temporal configurations among 20 late prehistoric locations. Through his analysis, Lipo [80, 83] demonstrated that data generated from the original collections are well suited for examining transmission. In his analysis, Lipo [80, 83] constructed deterministic seriations for the assemblages using a manual graphical technique and found that no single solution could be obtained using the 20 assemblages. Instead, fpsyg.2016.01503 the set of assemblages had to divided into 8 different spatial groups (Figs 9 and 10). These groups reflected the effects of local transmission among communities that overwhelms the effects of longer-range interaction within the region. Interestingly, two valid seriation solutions in the “Parkin” area (Groups 2 and 3 in Fig 10) overlap with one another in that they both share the assemblage 11-N-1, the Parkin site. Lipo [83] explained this result asPLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,19 /The IDSS Frequency Seriation AlgorithmFig 10. Spatial distribution of seriation groups with St. Francis and Memphis Assemblages consisting of Lipo [84] and Phillips et al. [10] samples. Labels for groups refer to seriation solutions numbered in Fig 9. While each seriation group also includes Holden Lake, this assemblage is removed here for visual clarity. The groups are strongly spatial in their configuration. Interestingly, the Parkin (11-N-1) assemblage falls into groups 2 and 3 suggesting that it served as a central node, possibly indicating emerging social complexity. doi:10.1371/journal.pone.0124942.gPLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,20 /The IDSS Frequency Seriation Algorithmthe effect of Parkin acting as a central “node” in a network and possibly indicative of emerging social complexity among otherwise functionally redundant settlements. While Lipo’s result demonstrates the potential for seriation as a means of explaining patterns of cultural transmission, the results and the approach as a whole are limited in practical utility for several reasons. First, the seriation results jir.2010.0097 were created by hand sorting following graphic methods outlined by Ford [6, 10] though assisted using spreadsheet macros in Microsoft Excel [83]. Consequently, we have no way of knowing whether the final sets of orders are the largest set or whether all possible solutions are represented. Second, while Lipo created confidence intervals for each class frequency and tested the pairwise ordering of assemblages, the inability to assess the chosen solution with respect to the entire search space limits confidence in the results. Finally, the us.

Practice of culture history in archaeology, we treat unimodality as a

Practice of culture history in archaeology, we treat unimodality as a construct that serves with continuity to help identify patterns that are potentially the product of cultural transmission. Second, generation of candidate solutions should be automated, so that seriation can be used as part of larger analyses (e.g.,PLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,8 /The IDSS Frequency Seriation AlgorithmFig 2. The results of a probabilistic s11606-015-3271-0 seriation analysis for a set of late prehistoric ceramics assemblages from the Memphis and St. Francis areas as described by Lipo [84] and Phillips and colleagues [10]. Here, the figures show the the results of correspondence analysis (CA) for the dataset in Table 2 following [85]. (A) The seriation order produced from the CA shown in standard centered bar format. (B) CA results shown with clusters as determined by hierarchical cluster analysis on the principlePLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,9 /The IDSS Frequency Seriation Algorithmcomponents. One can see that the change in the frequencies of types roughly follows a unimodal distribution, but there are numerous violations of unimodality as well. Data and R code for journal.pone.0174109 the correspondence analysis are available at https://github.com/mmadsen/lipomadsen2015-idss-seriation-paper. doi:10.1371/journal.pone.0124942.gspatial analysis, simulation studies of migration, trade, or cultural transmission). Third, the algorithm should provide error estimates and confidence bands where possible, to allow evaluation of the quality of a solution given the input data, and diagnosis of any violations of unimodality or continuity. Finally, the technique must be able to find all viable deterministic solutions given bounded and reasonable processing time for even relatively large sets of assemblage (e.g., 20 or 50), such that resampling or the bootstrap can be used to calculate error terms and evaluate the effects of sample size. These are not easy requirements to meet. In the space created by all the BMS-5 manufacturer possible orderings of assemblages, the vast majority of orders are invalid, as the combinations violate the conditions of the DFS method due to deviations from unimodality and/or continuity. Even with stricter constraints on possible solutions, valid candidates cannot be found by enumeration for more than a handful of assemblages. The search space must be “pruned” in some fashion to remove combinations that cannot possibly be part of a valid solution. Overview of the IDSS Algorithm. The technique we propose to accomplish these goals is called the Iterative Deterministic Seriation Solution (IDSS). IDSS builds DFS orders in an iterative process, starting with valid seriation solutions composed of the smallest possible number of assemblages and then employing these as building blocks for larger solutions. Solutions are grown from valid smaller solutions instead of enumerating possible combinations. We start with combinations of three assemblages (triples), the fewest number that can be evaluated in terms of the degree to which they meet the ARRY-334543MedChemExpress ARRY-334543 demands of the model. With three assemblages, we retain only those sets in which the frequencies for each of the classes show a steady increase, steady decrease, a middle “peak,” or no change at all (Fig 4). Assemblage orders that have frequencies that decrease then increase are eliminated as building blocks. The next step in the procedure is to use just the successful triples and see if any of the remaining assemblages.Practice of culture history in archaeology, we treat unimodality as a construct that serves with continuity to help identify patterns that are potentially the product of cultural transmission. Second, generation of candidate solutions should be automated, so that seriation can be used as part of larger analyses (e.g.,PLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,8 /The IDSS Frequency Seriation AlgorithmFig 2. The results of a probabilistic s11606-015-3271-0 seriation analysis for a set of late prehistoric ceramics assemblages from the Memphis and St. Francis areas as described by Lipo [84] and Phillips and colleagues [10]. Here, the figures show the the results of correspondence analysis (CA) for the dataset in Table 2 following [85]. (A) The seriation order produced from the CA shown in standard centered bar format. (B) CA results shown with clusters as determined by hierarchical cluster analysis on the principlePLOS ONE | DOI:10.1371/journal.pone.0124942 April 29,9 /The IDSS Frequency Seriation Algorithmcomponents. One can see that the change in the frequencies of types roughly follows a unimodal distribution, but there are numerous violations of unimodality as well. Data and R code for journal.pone.0174109 the correspondence analysis are available at https://github.com/mmadsen/lipomadsen2015-idss-seriation-paper. doi:10.1371/journal.pone.0124942.gspatial analysis, simulation studies of migration, trade, or cultural transmission). Third, the algorithm should provide error estimates and confidence bands where possible, to allow evaluation of the quality of a solution given the input data, and diagnosis of any violations of unimodality or continuity. Finally, the technique must be able to find all viable deterministic solutions given bounded and reasonable processing time for even relatively large sets of assemblage (e.g., 20 or 50), such that resampling or the bootstrap can be used to calculate error terms and evaluate the effects of sample size. These are not easy requirements to meet. In the space created by all the possible orderings of assemblages, the vast majority of orders are invalid, as the combinations violate the conditions of the DFS method due to deviations from unimodality and/or continuity. Even with stricter constraints on possible solutions, valid candidates cannot be found by enumeration for more than a handful of assemblages. The search space must be “pruned” in some fashion to remove combinations that cannot possibly be part of a valid solution. Overview of the IDSS Algorithm. The technique we propose to accomplish these goals is called the Iterative Deterministic Seriation Solution (IDSS). IDSS builds DFS orders in an iterative process, starting with valid seriation solutions composed of the smallest possible number of assemblages and then employing these as building blocks for larger solutions. Solutions are grown from valid smaller solutions instead of enumerating possible combinations. We start with combinations of three assemblages (triples), the fewest number that can be evaluated in terms of the degree to which they meet the demands of the model. With three assemblages, we retain only those sets in which the frequencies for each of the classes show a steady increase, steady decrease, a middle “peak,” or no change at all (Fig 4). Assemblage orders that have frequencies that decrease then increase are eliminated as building blocks. The next step in the procedure is to use just the successful triples and see if any of the remaining assemblages.

The hind tibiotarsal joints once a week. Each curve represents the

The hind tibiotarsal joints once a week. Each curve represents the mean of the study group. Asterisks denote significant difference from uninfected mice (P 0.05). Paraffin-embedded tissue sections were prepared from dbpAB/dbpAB (D; group 7) and dbpAB (E; group 8) infected and uninfected control (F; group 6) mice at 15 weeks of infection and stained for HE. Arrowheads indicate the synovial membrane, and asterisks indicate articular cartilage surface s11606-015-3271-0 in panels D and E. The original magnification in panels D and E is ?00 and in panel F ?0. Panel F indicates the anatomical structure shown in panels D and E. “Cef” get MK-1439 ceftriaxone treatment, “aT” anti-TNFalpha treatment. doi:10.1371/journal.pone.0121512.gSerology using the whole cell antigen and performed on post mortem serum samples indicated that all animals mounted a clear IgG response against both B. burgdorferi strains (Fig. 3A, groups 7 and 8). Antibodies against C6 peptide were significantly increased only in the samples of dbpAB/dbpAB infected mice (S1A Fig., groups 7 and 8). dbpAB/dbpAB infected micePLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,7 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTable 1. B. burgdorferi culture results of Experiment I at seven weeks of infection. Culture at 7 wk Group 1 2 3 4 5 Strain/treatment Uninfected fpsyg.2014.00822 dbpAB/dbpAB dbpAB/dbpA dbpAB/dbpB dbpAB Ear 0/2 4/4 8/8 5/8 0/2 Bladder 0/2 4/4 7/7a 8/8 2/2 Joint 0/2 4/4 7/8 8/8 2/a One sample not CI-1011 supplement available for culture doi:10.1371/journal.pone.0121512.tdeveloped significantly elevated antibody levels also against DbpA and B (S1B and C Fig., group 7). B. burgdorferi culture of post mortem tissue samples demonstrated widespread infection with positive culture results in all analysed tissues of dbpAB/dbpAB infected mice and in the tissues of three out of four dbpAB infected animals (Table 2, groups 7 and 8). Amplification of B. burgdorferi flaB and ospA genes using DNA extracted from joint tissue samples of dbpAB/dbpAB infected mice corroborated the presence of B. burgdorferi in the joints of all dbpAB/dbpAB infected and untreated mice (Table 3, group 7). Sensitivity of PCR appeared to be lower than the sensitivity of culture since 75 (? of ear samples of dbpAB/dbpAB infected mice that were all culture positive were positive in PCR. This was even more pronounced with the samples of dbpAB infected animals with only one out of three culture positive ear samples and none of the three culture positive bladder samples were PCR positive (Table 3, group 8). The results of the quantitative ospA PCR showed that there was no statistically significant difference in the bacterial load between the B. burgdorferi PCR positive joint samples of dbpAB/dbpAB and dbpAB infected mice (Fig. 4, groups 7 and 8). These results demonstrate that also the dbpAB strain is able to persistently infect mice, and that the bacterial load in the joints of dbpAB infected mice does not differ from the load of dbpAB/dbpAB infected mice at 15 weeks of infection.Effect of ceftriaxone and anti-TNF-alpha treatments on dissemination and arthritis developmentCeftriaxone was administered twice a day for five days during the third week of infection in subgroups of dbpAB/dbpAB and dbpAB infected mice (Fig. 1, groups 9?2). AntibioticTable 2. B. burgdorferi culture results of Experiment II at 6, 9 and 15 weeks of infection. Ear Culture Group 6 7 8 9 10 11 12 Strain/treatment Uninfected dbpAB/dbpAB dbpAB dbpAB/dbpAB + Cef2 dbpAB + Cef2 dbpA.The hind tibiotarsal joints once a week. Each curve represents the mean of the study group. Asterisks denote significant difference from uninfected mice (P 0.05). Paraffin-embedded tissue sections were prepared from dbpAB/dbpAB (D; group 7) and dbpAB (E; group 8) infected and uninfected control (F; group 6) mice at 15 weeks of infection and stained for HE. Arrowheads indicate the synovial membrane, and asterisks indicate articular cartilage surface s11606-015-3271-0 in panels D and E. The original magnification in panels D and E is ?00 and in panel F ?0. Panel F indicates the anatomical structure shown in panels D and E. “Cef” Ceftriaxone treatment, “aT” anti-TNFalpha treatment. doi:10.1371/journal.pone.0121512.gSerology using the whole cell antigen and performed on post mortem serum samples indicated that all animals mounted a clear IgG response against both B. burgdorferi strains (Fig. 3A, groups 7 and 8). Antibodies against C6 peptide were significantly increased only in the samples of dbpAB/dbpAB infected mice (S1A Fig., groups 7 and 8). dbpAB/dbpAB infected micePLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,7 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTable 1. B. burgdorferi culture results of Experiment I at seven weeks of infection. Culture at 7 wk Group 1 2 3 4 5 Strain/treatment Uninfected fpsyg.2014.00822 dbpAB/dbpAB dbpAB/dbpA dbpAB/dbpB dbpAB Ear 0/2 4/4 8/8 5/8 0/2 Bladder 0/2 4/4 7/7a 8/8 2/2 Joint 0/2 4/4 7/8 8/8 2/a One sample not available for culture doi:10.1371/journal.pone.0121512.tdeveloped significantly elevated antibody levels also against DbpA and B (S1B and C Fig., group 7). B. burgdorferi culture of post mortem tissue samples demonstrated widespread infection with positive culture results in all analysed tissues of dbpAB/dbpAB infected mice and in the tissues of three out of four dbpAB infected animals (Table 2, groups 7 and 8). Amplification of B. burgdorferi flaB and ospA genes using DNA extracted from joint tissue samples of dbpAB/dbpAB infected mice corroborated the presence of B. burgdorferi in the joints of all dbpAB/dbpAB infected and untreated mice (Table 3, group 7). Sensitivity of PCR appeared to be lower than the sensitivity of culture since 75 (? of ear samples of dbpAB/dbpAB infected mice that were all culture positive were positive in PCR. This was even more pronounced with the samples of dbpAB infected animals with only one out of three culture positive ear samples and none of the three culture positive bladder samples were PCR positive (Table 3, group 8). The results of the quantitative ospA PCR showed that there was no statistically significant difference in the bacterial load between the B. burgdorferi PCR positive joint samples of dbpAB/dbpAB and dbpAB infected mice (Fig. 4, groups 7 and 8). These results demonstrate that also the dbpAB strain is able to persistently infect mice, and that the bacterial load in the joints of dbpAB infected mice does not differ from the load of dbpAB/dbpAB infected mice at 15 weeks of infection.Effect of ceftriaxone and anti-TNF-alpha treatments on dissemination and arthritis developmentCeftriaxone was administered twice a day for five days during the third week of infection in subgroups of dbpAB/dbpAB and dbpAB infected mice (Fig. 1, groups 9?2). AntibioticTable 2. B. burgdorferi culture results of Experiment II at 6, 9 and 15 weeks of infection. Ear Culture Group 6 7 8 9 10 11 12 Strain/treatment Uninfected dbpAB/dbpAB dbpAB dbpAB/dbpAB + Cef2 dbpAB + Cef2 dbpA.

The hind tibiotarsal joints once a week. Each curve represents the

The hind tibiotarsal joints once a week. Each curve represents the mean of the study group. Asterisks denote significant difference from uninfected mice (P 0.05). Paraffin-embedded tissue sections were prepared from dbpAB/dbpAB (D; group 7) and dbpAB (E; group 8) infected and uninfected control (F; group 6) mice at 15 weeks of infection and stained for HE. Arrowheads indicate the synovial membrane, and asterisks indicate articular cartilage surface s11606-015-3271-0 in panels D and E. The original magnification in panels D and E is ?00 and in panel F ?0. Panel F indicates the anatomical structure shown in panels D and E. “Cef” Ceftriaxone treatment, “aT” anti-TNFalpha treatment. doi:10.1371/journal.pone.0121512.gSerology using the whole cell antigen and performed on post mortem serum Cyanein biological activity samples indicated that all animals mounted a clear IgG response against both B. burgdorferi strains (Fig. 3A, groups 7 and 8). Antibodies against C6 peptide were significantly increased only in the samples of dbpAB/dbpAB infected mice (S1A Fig., groups 7 and 8). dbpAB/dbpAB infected micePLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,7 /DbpA and B Promote Arthritis and Post-Treatment Persistence in buy XAV-939 MiceTable 1. B. burgdorferi culture results of Experiment I at seven weeks of infection. Culture at 7 wk Group 1 2 3 4 5 Strain/treatment Uninfected fpsyg.2014.00822 dbpAB/dbpAB dbpAB/dbpA dbpAB/dbpB dbpAB Ear 0/2 4/4 8/8 5/8 0/2 Bladder 0/2 4/4 7/7a 8/8 2/2 Joint 0/2 4/4 7/8 8/8 2/a One sample not available for culture doi:10.1371/journal.pone.0121512.tdeveloped significantly elevated antibody levels also against DbpA and B (S1B and C Fig., group 7). B. burgdorferi culture of post mortem tissue samples demonstrated widespread infection with positive culture results in all analysed tissues of dbpAB/dbpAB infected mice and in the tissues of three out of four dbpAB infected animals (Table 2, groups 7 and 8). Amplification of B. burgdorferi flaB and ospA genes using DNA extracted from joint tissue samples of dbpAB/dbpAB infected mice corroborated the presence of B. burgdorferi in the joints of all dbpAB/dbpAB infected and untreated mice (Table 3, group 7). Sensitivity of PCR appeared to be lower than the sensitivity of culture since 75 (? of ear samples of dbpAB/dbpAB infected mice that were all culture positive were positive in PCR. This was even more pronounced with the samples of dbpAB infected animals with only one out of three culture positive ear samples and none of the three culture positive bladder samples were PCR positive (Table 3, group 8). The results of the quantitative ospA PCR showed that there was no statistically significant difference in the bacterial load between the B. burgdorferi PCR positive joint samples of dbpAB/dbpAB and dbpAB infected mice (Fig. 4, groups 7 and 8). These results demonstrate that also the dbpAB strain is able to persistently infect mice, and that the bacterial load in the joints of dbpAB infected mice does not differ from the load of dbpAB/dbpAB infected mice at 15 weeks of infection.Effect of ceftriaxone and anti-TNF-alpha treatments on dissemination and arthritis developmentCeftriaxone was administered twice a day for five days during the third week of infection in subgroups of dbpAB/dbpAB and dbpAB infected mice (Fig. 1, groups 9?2). AntibioticTable 2. B. burgdorferi culture results of Experiment II at 6, 9 and 15 weeks of infection. Ear Culture Group 6 7 8 9 10 11 12 Strain/treatment Uninfected dbpAB/dbpAB dbpAB dbpAB/dbpAB + Cef2 dbpAB + Cef2 dbpA.The hind tibiotarsal joints once a week. Each curve represents the mean of the study group. Asterisks denote significant difference from uninfected mice (P 0.05). Paraffin-embedded tissue sections were prepared from dbpAB/dbpAB (D; group 7) and dbpAB (E; group 8) infected and uninfected control (F; group 6) mice at 15 weeks of infection and stained for HE. Arrowheads indicate the synovial membrane, and asterisks indicate articular cartilage surface s11606-015-3271-0 in panels D and E. The original magnification in panels D and E is ?00 and in panel F ?0. Panel F indicates the anatomical structure shown in panels D and E. “Cef” Ceftriaxone treatment, “aT” anti-TNFalpha treatment. doi:10.1371/journal.pone.0121512.gSerology using the whole cell antigen and performed on post mortem serum samples indicated that all animals mounted a clear IgG response against both B. burgdorferi strains (Fig. 3A, groups 7 and 8). Antibodies against C6 peptide were significantly increased only in the samples of dbpAB/dbpAB infected mice (S1A Fig., groups 7 and 8). dbpAB/dbpAB infected micePLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,7 /DbpA and B Promote Arthritis and Post-Treatment Persistence in MiceTable 1. B. burgdorferi culture results of Experiment I at seven weeks of infection. Culture at 7 wk Group 1 2 3 4 5 Strain/treatment Uninfected fpsyg.2014.00822 dbpAB/dbpAB dbpAB/dbpA dbpAB/dbpB dbpAB Ear 0/2 4/4 8/8 5/8 0/2 Bladder 0/2 4/4 7/7a 8/8 2/2 Joint 0/2 4/4 7/8 8/8 2/a One sample not available for culture doi:10.1371/journal.pone.0121512.tdeveloped significantly elevated antibody levels also against DbpA and B (S1B and C Fig., group 7). B. burgdorferi culture of post mortem tissue samples demonstrated widespread infection with positive culture results in all analysed tissues of dbpAB/dbpAB infected mice and in the tissues of three out of four dbpAB infected animals (Table 2, groups 7 and 8). Amplification of B. burgdorferi flaB and ospA genes using DNA extracted from joint tissue samples of dbpAB/dbpAB infected mice corroborated the presence of B. burgdorferi in the joints of all dbpAB/dbpAB infected and untreated mice (Table 3, group 7). Sensitivity of PCR appeared to be lower than the sensitivity of culture since 75 (? of ear samples of dbpAB/dbpAB infected mice that were all culture positive were positive in PCR. This was even more pronounced with the samples of dbpAB infected animals with only one out of three culture positive ear samples and none of the three culture positive bladder samples were PCR positive (Table 3, group 8). The results of the quantitative ospA PCR showed that there was no statistically significant difference in the bacterial load between the B. burgdorferi PCR positive joint samples of dbpAB/dbpAB and dbpAB infected mice (Fig. 4, groups 7 and 8). These results demonstrate that also the dbpAB strain is able to persistently infect mice, and that the bacterial load in the joints of dbpAB infected mice does not differ from the load of dbpAB/dbpAB infected mice at 15 weeks of infection.Effect of ceftriaxone and anti-TNF-alpha treatments on dissemination and arthritis developmentCeftriaxone was administered twice a day for five days during the third week of infection in subgroups of dbpAB/dbpAB and dbpAB infected mice (Fig. 1, groups 9?2). AntibioticTable 2. B. burgdorferi culture results of Experiment II at 6, 9 and 15 weeks of infection. Ear Culture Group 6 7 8 9 10 11 12 Strain/treatment Uninfected dbpAB/dbpAB dbpAB dbpAB/dbpAB + Cef2 dbpAB + Cef2 dbpA.

Psy that are often difficult to manage, health-related stigma associated with

Psy that are often difficult to manage, health-related stigma associated with narcolepsy is likely to have a negative impact on the quality of life of young adults and is likely partially responsible for the depression, occupational and academic difficulties and personal and social problems reported by younger patients. The present study builds upon previous research to provide a better understanding of the impact of stigma and related variables associated with HRQOL in young adults with narcolepsy. We sought to compare young adults with and without narcolepsy on health-related stigma, mood and health-related quality of life, determine relationships among the variables and identify predictors of functioning in young adults with narcolepsy. Results providePLOS ONE | DOI:10.1371/journal.pone.0122478 April 21,2 /Stigma in Young Adults with Narcolepsyevidence for further research on stigma and the development of interventions for people with narcolepsy.Materials and Methods Design SampleFor this cross sectional ZM241385 site Survey study we utilized data collected by Merritt and colleagues in 2002[18]. The sample consisted of young adults with narcolepsy 18?7 years of age who contacted the University of Illinois at Chicago, Center for Narcolepsy Research asking that they be placed on the mailing list and indicating an interest in participating in research. An acquaintance approach was used to obtain a control group of young adults without narcolepsy[19]. Young adults with narcolepsy answering an advertisement by phone and agreeing to participate were mailed a packet that included the questionnaire along with a cover letter and a selfaddressed postage paid envelope. The questionnaire included demographic, socioeconomic and disease-related information and a composite of instruments including the Short Form 36 [20], the modified Social Impact Scale (MSIS)[21], the Hospital Anxiety and Depression Scale (HADS)[22,23], the Epworth Sleepiness Scale (ESS)[24] and the Pittsburgh Sleep Quality Index[25].Ethics StatementThe principal investigator provided information In the cover letter explaining the purpose and procedures of the study and confidentiality information generally found in the consent form. Also included in the cover letter was a statement that participation in the study was voluntary and that by returning the completed survey, the subject provided consent to be included in the study. Survey data were anonymized and de-identified. The study was approved by the University of Illinois at Chicago Institutional Review Board.MeasuresHealth-related stigma was measured using the Stigma and Social Impact Scale (SSIS)[21] and the Disclosure Concerns scale[26] The SSIS includes 24 items with a 4-point likert response scale (strongly agree, agree, disagree and strongly disagree). It consists of four subscales: social EPZ-5676 price rejection (9 items), financial insecurity (3 items), internalized shame (5 items) and social isolation (7 items) experienced in the past 4 weeks. Social rejection signifies the feelings of social and job rejection experienced by the respondent. Financial insecurity captures feelings of the financial consequences of discrimination including income and job security. Internalized shame indicates the extent to which the participant has feelings of being different from others, blames his/her self for the illness and feels the need to conceal the illness. Social isolation captures feelings of low self-esteem and loneliness[21]. The items were reworded o.Psy that are often difficult to manage, health-related stigma associated with narcolepsy is likely to have a negative impact on the quality of life of young adults and is likely partially responsible for the depression, occupational and academic difficulties and personal and social problems reported by younger patients. The present study builds upon previous research to provide a better understanding of the impact of stigma and related variables associated with HRQOL in young adults with narcolepsy. We sought to compare young adults with and without narcolepsy on health-related stigma, mood and health-related quality of life, determine relationships among the variables and identify predictors of functioning in young adults with narcolepsy. Results providePLOS ONE | DOI:10.1371/journal.pone.0122478 April 21,2 /Stigma in Young Adults with Narcolepsyevidence for further research on stigma and the development of interventions for people with narcolepsy.Materials and Methods Design SampleFor this cross sectional survey study we utilized data collected by Merritt and colleagues in 2002[18]. The sample consisted of young adults with narcolepsy 18?7 years of age who contacted the University of Illinois at Chicago, Center for Narcolepsy Research asking that they be placed on the mailing list and indicating an interest in participating in research. An acquaintance approach was used to obtain a control group of young adults without narcolepsy[19]. Young adults with narcolepsy answering an advertisement by phone and agreeing to participate were mailed a packet that included the questionnaire along with a cover letter and a selfaddressed postage paid envelope. The questionnaire included demographic, socioeconomic and disease-related information and a composite of instruments including the Short Form 36 [20], the modified Social Impact Scale (MSIS)[21], the Hospital Anxiety and Depression Scale (HADS)[22,23], the Epworth Sleepiness Scale (ESS)[24] and the Pittsburgh Sleep Quality Index[25].Ethics StatementThe principal investigator provided information In the cover letter explaining the purpose and procedures of the study and confidentiality information generally found in the consent form. Also included in the cover letter was a statement that participation in the study was voluntary and that by returning the completed survey, the subject provided consent to be included in the study. Survey data were anonymized and de-identified. The study was approved by the University of Illinois at Chicago Institutional Review Board.MeasuresHealth-related stigma was measured using the Stigma and Social Impact Scale (SSIS)[21] and the Disclosure Concerns scale[26] The SSIS includes 24 items with a 4-point likert response scale (strongly agree, agree, disagree and strongly disagree). It consists of four subscales: social rejection (9 items), financial insecurity (3 items), internalized shame (5 items) and social isolation (7 items) experienced in the past 4 weeks. Social rejection signifies the feelings of social and job rejection experienced by the respondent. Financial insecurity captures feelings of the financial consequences of discrimination including income and job security. Internalized shame indicates the extent to which the participant has feelings of being different from others, blames his/her self for the illness and feels the need to conceal the illness. Social isolation captures feelings of low self-esteem and loneliness[21]. The items were reworded o.

Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed

Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed in vivo that 10?20 compressive strain of cartilage led to about 5?3 cell width strain, depending on the area the cells were located [12]. Similarly, it has recently been calculated that the Green-Lagrange strain for cell width increased by 0.17 ?0.02 when bovine cartilage tissue was compressed with a 15 nominal tissue strain [91]. Extreme tissue strains of 80 cartilage compression increased the cell strain only by an additional 2? [95,96]. This suggests that chondrocytes in vivo are not subjected to more than 15 cell elongation. However, one has to consider that chondrocytes come from different layers within articular cartilage. Within these layers cells experience different physical forces and may therefore respond differently to the same strain magnitudes. Nonetheless, as showed in two of the reviewed papers, chondrocytes might also tolerate higher strains (20 ; 24 ) without inducing catabolic actions, although these strains might rather be un-physiologic [14,52]. There is a fine balance between anabolic and catabolic actions in chondrocytes in response to CTS. We suggest that in a non-inflammatory environment loading protocols below 3 strain, 0.17 Hz and 2 h result in weak or no biological responses. Loading protocols between 3?0 strain, 0.17 Hz–0.5 Hz and 2?2 h tend to induce anabolic responses, whereas above 10 strain, 0.5 Hz and 12 h, catabolic events occur. However, this review not only shows that each of the three loading parameters (magnitude, frequency, duration) but also that the environment of the cell contributes to the shift towards either anabolic or catabolic actions. To provide better comparability of studies and better transition to three-dimensional conditions, we suggest considering the following hints in the future: Loading conditions should be as physiological as possible and should include pauses. Therefore, we advise to apply loading frequencies between 0.5 and 2.5 Hz, loading magnitudes between 0.5 and 15 , and loading durations shorter than 12 h. Further, culture plates should be uncoated or coated with the cartilagespecific collagen II. Data should be collected not only immediately after the last loading cycle but also after a recovery time. All parameters that could affect the cellular PX-478 site outcome should be explained in details.PLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,20 /Cyclic Tensile Strain and MK-5172 site chondrocyte MetabolismConclusionResults from in vitro experiments with CTS disclose further information about the effect of mechanical signals on the biological response of chondrocytes. Many factors are involved in the synthesis and remodeling of the ECM in response to loading. It is important to look not only at single isolated parameters and to combine information from different studies. A better understanding of the relationship between specific loading parameters and chondrocyte response will be useful for the development of tissue engineered cartilage. Furthermore, the simulation of an inflammatory environment allows new insights into the anabolic capabilities of specific loading protocols in rehabilitation and therapy of degenerative joint disease like osteoarthritis.Supporting InformationS1 Checklist. PRISMA checklist. (PDF)Author ContributionsConceived and designed the experiments: JB FZ GB AN. Analyzed the data: JB FZ GB AN. Wrote the paper: JB FZ GB AN. Literature search: JB AN.Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed in vivo that 10?20 compressive strain of cartilage led to about 5?3 cell width strain, depending on the area the cells were located [12]. Similarly, it has recently been calculated that the Green-Lagrange strain for cell width increased by 0.17 ?0.02 when bovine cartilage tissue was compressed with a 15 nominal tissue strain [91]. Extreme tissue strains of 80 cartilage compression increased the cell strain only by an additional 2? [95,96]. This suggests that chondrocytes in vivo are not subjected to more than 15 cell elongation. However, one has to consider that chondrocytes come from different layers within articular cartilage. Within these layers cells experience different physical forces and may therefore respond differently to the same strain magnitudes. Nonetheless, as showed in two of the reviewed papers, chondrocytes might also tolerate higher strains (20 ; 24 ) without inducing catabolic actions, although these strains might rather be un-physiologic [14,52]. There is a fine balance between anabolic and catabolic actions in chondrocytes in response to CTS. We suggest that in a non-inflammatory environment loading protocols below 3 strain, 0.17 Hz and 2 h result in weak or no biological responses. Loading protocols between 3?0 strain, 0.17 Hz–0.5 Hz and 2?2 h tend to induce anabolic responses, whereas above 10 strain, 0.5 Hz and 12 h, catabolic events occur. However, this review not only shows that each of the three loading parameters (magnitude, frequency, duration) but also that the environment of the cell contributes to the shift towards either anabolic or catabolic actions. To provide better comparability of studies and better transition to three-dimensional conditions, we suggest considering the following hints in the future: Loading conditions should be as physiological as possible and should include pauses. Therefore, we advise to apply loading frequencies between 0.5 and 2.5 Hz, loading magnitudes between 0.5 and 15 , and loading durations shorter than 12 h. Further, culture plates should be uncoated or coated with the cartilagespecific collagen II. Data should be collected not only immediately after the last loading cycle but also after a recovery time. All parameters that could affect the cellular outcome should be explained in details.PLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,20 /Cyclic Tensile Strain and Chondrocyte MetabolismConclusionResults from in vitro experiments with CTS disclose further information about the effect of mechanical signals on the biological response of chondrocytes. Many factors are involved in the synthesis and remodeling of the ECM in response to loading. It is important to look not only at single isolated parameters and to combine information from different studies. A better understanding of the relationship between specific loading parameters and chondrocyte response will be useful for the development of tissue engineered cartilage. Furthermore, the simulation of an inflammatory environment allows new insights into the anabolic capabilities of specific loading protocols in rehabilitation and therapy of degenerative joint disease like osteoarthritis.Supporting InformationS1 Checklist. PRISMA checklist. (PDF)Author ContributionsConceived and designed the experiments: JB FZ GB AN. Analyzed the data: JB FZ GB AN. Wrote the paper: JB FZ GB AN. Literature search: JB AN.

ManuscriptAcknowledgmentsWe would like to thank all the community members in Salvador

ManuscriptAcknowledgmentsWe would like to thank all the community members in Salvador who participated in the study. We also thank Milena Soares and 3-MA web Soraia Machado Cordeiro for advice during laboratory analysis. This work was supported by grants from the Brazilian National Research Council (482755/order PF-04418948 2010-5), the Research Foundation for the State of Bahia (FAPESB: 1431040054051) and the National Institutes of Health (TW007303). DMW is supported by the Global Health Equity Scholars training program (TW009338), The Bill and Melinda Gates Foundation (OPP1114733), the Yale Program on Aging (P30AG021342), and NIH/NIAID (R56 AI110449) Conflicts of Interest DMW is the Principal Investigator of an Investigator Initiated Research grant from Pfizer to Yale University and has received consulting fees from Merck and Pfizer.Vaccine. Author manuscript; available in PMC 2017 February 03.Menezes et al.Page
HHS Public AccessAuthor manuscriptHypertension. Author manuscript; available in PMC 2016 June 08.Published in final edited form as: Hypertension. 2015 April ; 65(4): 813?20. doi:10.1161/HYPERTENSIONAHA.114.04533.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptTranscription Factor Avian Erythroblastosis Virus E26 Oncogen Homolog-1 Is a Novel Mediator of Renal Injury in Salt-Sensitive HypertensionWenguang Feng, Phillip Chumley, Minolfa C. Prieto, Kayoko Miyada, Dale M. Seth, Huma Fatima, Ping Hua, Gabriel Rezonzew, Paul W. Sanders, and Edgar A. Jaimes 1,1-Dimethylbiguanide hydrochlorideMedChemExpress 1,1-Dimethylbiguanide hydrochloride Division of Nephrology (W.F., P.C., P.H., G.R., P.W.S.) and Department of Pathology (H.F.), University of Alabama at Birmingham; Department of Physiology, Tulane University, New Orleans, LA (M.C.P., K.M., D.M.S.); Nephrology Section, VA Medical Center, Birmingham, AL (P.W.S., E.A.J.); and Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY (E.A.J.)AbstractTranscription factor E26 transformation-specific sequence-1 (ETS-1) is a transcription factor that regulates the expression of a variety of genes, including growth factors, chemokines, and adhesion molecules. We recently demonstrated that angiotensin II increases the order UNC0642 glomerular expression of ETS-1 and that blockade of ETS-1 ameliorates the profibrotic and proinflammatory effects of angiotensin II. The Dahl salt-sensitive rat is a paradigm of salt-sensitive hypertension associated with local activation of the renin ngiotensin system. In these studies, we determined whether: (1) salt-sensitive hypertension is associated with renal expression of ETS-1 and (2) ETS-1 participates in the development of end-organ injury in salt-sensitive hypertension. Dahl salt-sensitive rats were fed a normal-salt diet (0.5 NaCl diet) or a high-salt diet (4 NaCl) for 4 weeks. Separate groups on high-salt diet received an ETS-1 dominant negative peptide (10mg/kg/day), an inactive ETS-1 mutant peptide (10mg/kg/d), the angiotensin II type 1 receptor blocker candesartan (10 mg/kg/d), or the combination high-salt diet/dominant-negative peptide/angiotensin II type 1 receptor blocker for 4 weeks. High-salt diet rats had a significant increase in the glomerular expression of the phosphorylated ETS-1 that was prevented by angiotensin II type 1 receptor blocker. ETS-1 blockade reduced proteinuria, glomerular injury score, fibronectin expression, urinary transforming growth factor- excretion, and macrophage infiltration. Angiotensin II type 1 receptor blocker reduced proteinuria, glomerular injury score, and macrophage infiltration, whereas concomitan.ManuscriptAcknowledgmentsWe would like to thank all the community members in Salvador who participated in the study. We also thank Milena Soares and Soraia Machado Cordeiro for advice during laboratory analysis. This work was supported by grants from the Brazilian National Research Council (482755/2010-5), the Research Foundation for the State of Bahia (FAPESB: 1431040054051) and the National Institutes of Health (TW007303). DMW is supported by the Global Health Equity Scholars training program (TW009338), The Bill and Melinda Gates Foundation (OPP1114733), the Yale Program on Aging (P30AG021342), and NIH/NIAID (R56 AI110449) Conflicts of Interest DMW is the Principal Investigator of an Investigator Initiated Research grant from Pfizer to Yale University and has received consulting fees from Merck and Pfizer.Vaccine. Author manuscript; available in PMC 2017 February 03.Menezes et al.Page
HHS Public AccessAuthor manuscriptHypertension. Author manuscript; available in PMC 2016 June 08.Published in final edited form as: Hypertension. 2015 April ; 65(4): 813?20. doi:10.1161/HYPERTENSIONAHA.114.04533.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptTranscription Factor Avian Erythroblastosis Virus E26 Oncogen Homolog-1 Is a Novel Mediator of Renal Injury in Salt-Sensitive HypertensionWenguang Feng, Phillip Chumley, Minolfa C. Prieto, Kayoko Miyada, Dale M. Seth, Huma Fatima, Ping Hua, Gabriel Rezonzew, Paul W. Sanders, and Edgar A. Jaimes Division of Nephrology (W.F., P.C., P.H., G.R., P.W.S.) and Department of Pathology (H.F.), University of Alabama at Birmingham; Department of Physiology, Tulane University, New Orleans, LA (M.C.P., K.M., D.M.S.); Nephrology Section, VA Medical Center, Birmingham, AL (P.W.S., E.A.J.); and Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY (E.A.J.)AbstractTranscription factor E26 transformation-specific sequence-1 (ETS-1) is a transcription factor that regulates the expression of a variety of genes, including growth factors, chemokines, and adhesion molecules. We recently demonstrated that angiotensin II increases the glomerular expression of ETS-1 and that blockade of ETS-1 ameliorates the profibrotic and proinflammatory effects of angiotensin II. The Dahl salt-sensitive rat is a paradigm of salt-sensitive hypertension associated with local activation of the renin ngiotensin system. In these studies, we determined whether: (1) salt-sensitive hypertension is associated with renal expression of ETS-1 and (2) ETS-1 participates in the development of end-organ injury in salt-sensitive hypertension. Dahl salt-sensitive rats were fed a normal-salt diet (0.5 NaCl diet) or a high-salt diet (4 NaCl) for 4 weeks. Separate groups on high-salt diet received an ETS-1 dominant negative peptide (10mg/kg/day), an inactive ETS-1 mutant peptide (10mg/kg/d), the angiotensin II type 1 receptor blocker candesartan (10 mg/kg/d), or the combination high-salt diet/dominant-negative peptide/angiotensin II type 1 receptor blocker for 4 weeks. High-salt diet rats had a significant increase in the glomerular expression of the phosphorylated ETS-1 that was prevented by angiotensin II type 1 receptor blocker. ETS-1 blockade reduced proteinuria, glomerular injury score, fibronectin expression, urinary transforming growth factor- excretion, and macrophage infiltration. Angiotensin II type 1 receptor blocker reduced proteinuria, glomerular injury score, and macrophage infiltration, whereas concomitan.ManuscriptAcknowledgmentsWe would like to thank all the community members in Salvador who participated in the study. We also thank Milena Soares and Soraia Machado Cordeiro for advice during laboratory analysis. This work was supported by grants from the Brazilian National Research Council (482755/2010-5), the Research Foundation for the State of Bahia (FAPESB: 1431040054051) and the National Institutes of Health (TW007303). DMW is supported by the Global Health Equity Scholars training program (TW009338), The Bill and Melinda Gates Foundation (OPP1114733), the Yale Program on Aging (P30AG021342), and NIH/NIAID (R56 AI110449) Conflicts of Interest DMW is the Principal Investigator of an Investigator Initiated Research grant from Pfizer to Yale University and has received consulting fees from Merck and Pfizer.Vaccine. Author manuscript; available in PMC 2017 February 03.Menezes et al.Page
HHS Public AccessAuthor manuscriptHypertension. Author manuscript; available in PMC 2016 June 08.Published in final edited form as: Hypertension. 2015 April ; 65(4): 813?20. doi:10.1161/HYPERTENSIONAHA.114.04533.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptTranscription Factor Avian Erythroblastosis Virus E26 Oncogen Homolog-1 Is a Novel Mediator of Renal Injury in Salt-Sensitive HypertensionWenguang Feng, Phillip Chumley, Minolfa C. Prieto, Kayoko Miyada, Dale M. Seth, Huma Fatima, Ping Hua, Gabriel Rezonzew, Paul W. Sanders, and Edgar A. Jaimes Division of Nephrology (W.F., P.C., P.H., G.R., P.W.S.) and Department of Pathology (H.F.), University of Alabama at Birmingham; Department of Physiology, Tulane University, New Orleans, LA (M.C.P., K.M., D.M.S.); Nephrology Section, VA Medical Center, Birmingham, AL (P.W.S., E.A.J.); and Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY (E.A.J.)AbstractTranscription factor E26 transformation-specific sequence-1 (ETS-1) is a transcription factor that regulates the expression of a variety of genes, including growth factors, chemokines, and adhesion molecules. We recently demonstrated that angiotensin II increases the glomerular expression of ETS-1 and that blockade of ETS-1 ameliorates the profibrotic and proinflammatory effects of angiotensin II. The Dahl salt-sensitive rat is a paradigm of salt-sensitive hypertension associated with local activation of the renin ngiotensin system. In these studies, we determined whether: (1) salt-sensitive hypertension is associated with renal expression of ETS-1 and (2) ETS-1 participates in the development of end-organ injury in salt-sensitive hypertension. Dahl salt-sensitive rats were fed a normal-salt diet (0.5 NaCl diet) or a high-salt diet (4 NaCl) for 4 weeks. Separate groups on high-salt diet received an ETS-1 dominant negative peptide (10mg/kg/day), an inactive ETS-1 mutant peptide (10mg/kg/d), the angiotensin II type 1 receptor blocker candesartan (10 mg/kg/d), or the combination high-salt diet/dominant-negative peptide/angiotensin II type 1 receptor blocker for 4 weeks. High-salt diet rats had a significant increase in the glomerular expression of the phosphorylated ETS-1 that was prevented by angiotensin II type 1 receptor blocker. ETS-1 blockade reduced proteinuria, glomerular injury score, fibronectin expression, urinary transforming growth factor- excretion, and macrophage infiltration. Angiotensin II type 1 receptor blocker reduced proteinuria, glomerular injury score, and macrophage infiltration, whereas concomitan.ManuscriptAcknowledgmentsWe would like to thank all the community members in Salvador who participated in the study. We also thank Milena Soares and Soraia Machado Cordeiro for advice during laboratory analysis. This work was supported by grants from the Brazilian National Research Council (482755/2010-5), the Research Foundation for the State of Bahia (FAPESB: 1431040054051) and the National Institutes of Health (TW007303). DMW is supported by the Global Health Equity Scholars training program (TW009338), The Bill and Melinda Gates Foundation (OPP1114733), the Yale Program on Aging (P30AG021342), and NIH/NIAID (R56 AI110449) Conflicts of Interest DMW is the Principal Investigator of an Investigator Initiated Research grant from Pfizer to Yale University and has received consulting fees from Merck and Pfizer.Vaccine. Author manuscript; available in PMC 2017 February 03.Menezes et al.Page
HHS Public AccessAuthor manuscriptHypertension. Author manuscript; available in PMC 2016 June 08.Published in final edited form as: Hypertension. 2015 April ; 65(4): 813?20. doi:10.1161/HYPERTENSIONAHA.114.04533.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptTranscription Factor Avian Erythroblastosis Virus E26 Oncogen Homolog-1 Is a Novel Mediator of Renal Injury in Salt-Sensitive HypertensionWenguang Feng, Phillip Chumley, Minolfa C. Prieto, Kayoko Miyada, Dale M. Seth, Huma Fatima, Ping Hua, Gabriel Rezonzew, Paul W. Sanders, and Edgar A. Jaimes Division of Nephrology (W.F., P.C., P.H., G.R., P.W.S.) and Department of Pathology (H.F.), University of Alabama at Birmingham; Department of Physiology, Tulane University, New Orleans, LA (M.C.P., K.M., D.M.S.); Nephrology Section, VA Medical Center, Birmingham, AL (P.W.S., E.A.J.); and Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY (E.A.J.)AbstractTranscription factor E26 transformation-specific sequence-1 (ETS-1) is a transcription factor that regulates the expression of a variety of genes, including growth factors, chemokines, and adhesion molecules. We recently demonstrated that angiotensin II increases the glomerular expression of ETS-1 and that blockade of ETS-1 ameliorates the profibrotic and proinflammatory effects of angiotensin II. The Dahl salt-sensitive rat is a paradigm of salt-sensitive hypertension associated with local activation of the renin ngiotensin system. In these studies, we determined whether: (1) salt-sensitive hypertension is associated with renal expression of ETS-1 and (2) ETS-1 participates in the development of end-organ injury in salt-sensitive hypertension. Dahl salt-sensitive rats were fed a normal-salt diet (0.5 NaCl diet) or a high-salt diet (4 NaCl) for 4 weeks. Separate groups on high-salt diet received an ETS-1 dominant negative peptide (10mg/kg/day), an inactive ETS-1 mutant peptide (10mg/kg/d), the angiotensin II type 1 receptor blocker candesartan (10 mg/kg/d), or the combination high-salt diet/dominant-negative peptide/angiotensin II type 1 receptor blocker for 4 weeks. High-salt diet rats had a significant increase in the glomerular expression of the phosphorylated ETS-1 that was prevented by angiotensin II type 1 receptor blocker. ETS-1 blockade reduced proteinuria, glomerular injury score, fibronectin expression, urinary transforming growth factor- excretion, and macrophage infiltration. Angiotensin II type 1 receptor blocker reduced proteinuria, glomerular injury score, and macrophage infiltration, whereas concomitan.

Although there were no detectable changes in levels of measured cytokines

Although there were no detectable changes in levels of measured cytokines111. Epidural anesthesia reduces the plasma levels of norepinephrine during surgery when compared to general anesthesia112. This holds true when combined general and epidural anesthesia is compared to general anesthesia alone113. Norepinephrine and epinephrine induce vasoconstriction in the microcirculation114 and also have effects on subsequent biological processes that influence wound repair, such as angiogenesis and inflammation. For example, norepinephrine significantly increased secretion of the angiogenic factor VEGF by ovarian cancer and melanoma cell lines115, 116. Furthermore, epinephrine suppresses phagocytosis of soluble immune complexes (aggregated gamma-globulin) by macrophages in a dosedependent manner117 (Figure 4). IIID2. Duvoglustat web volatile anesthetics agents–Volatile anesthetic agents have several contradictory effects on microcirculatory flow. They decrease flow in the microcirculation by reducing arterial perfusion pressure and depressing myocardial contractility. At the same time these agents can increase flow in the microcirculation by inducing a vasodilatory response118. As a result, clinically useful concentrations of volatile agents will often produce systemic purchase Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone hypotension and decrease regional tissue perfusion in a tissue and agent specific manner119. Muscle perfusion under anesthesia with volatile agents is better maintained in young subjects than in aged subjects120. Not all effects of inhalation anesthesia are detrimental to tissue repair (Figure 5). Volatile anesthetics protect against ischemia-reperfusion injury of several organs (heart121, liver122, kidney123 and potentially others) by reducing necrosis and inflammation124. Several lines of evidence suggest that inhalation anesthetics exert their effects by affecting the microcirculation and influencing subsequent angiogenesis. For example, exposure to volatile anesthetics stimulates growth and proliferation of endothelial progenitor cells125. Volatile anesthetics, at clinically relevant doses, block transcription factor Hypoxia-inducible factor-1 activity and expression of its downstream target genes. Hypoxia-inducible factor-1 is a transcriptional regulator of VEGF expression126 and mediates angiogenic responses to reduced oxygen availability127. When renal proximal tubule cells were exposed to volatile anesthetics for sixteen hours there was increased production and release of TGF-1, a potent stimulator of extracellular matrix synthesis, into the cell culture media. The role of TGF-1 in the protective effect of volatile agents on ischemic injury to the kidney was specifically demonstrated in vivo – mice heterozygous for TGF-1 (TGF-1) were not protected from ischemia reperfusion injury by sevoflurane and a neutralizing TGF-1 antibody blockedAnesthesiology. Author manuscript; available in PMC 2015 March 01.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptBentov and ReedPagerenal protection with sevoflurane in TGF-1 mice128. Despite the data above, it is worth noting that volatile anesthetic agents differ in their effects on the microcirculation with respect to specific agents (desflurane versus isoflurane versus sevoflurane), target organs (heart versus kidney versus splanchnic), and clinical states (healthy versus sepsis versus hemorrhagic states)129. Consequently, we cannot make meaningful recommendations regarding volatile anesthetics and wound healing outcomes. III.Although there were no detectable changes in levels of measured cytokines111. Epidural anesthesia reduces the plasma levels of norepinephrine during surgery when compared to general anesthesia112. This holds true when combined general and epidural anesthesia is compared to general anesthesia alone113. Norepinephrine and epinephrine induce vasoconstriction in the microcirculation114 and also have effects on subsequent biological processes that influence wound repair, such as angiogenesis and inflammation. For example, norepinephrine significantly increased secretion of the angiogenic factor VEGF by ovarian cancer and melanoma cell lines115, 116. Furthermore, epinephrine suppresses phagocytosis of soluble immune complexes (aggregated gamma-globulin) by macrophages in a dosedependent manner117 (Figure 4). IIID2. Volatile anesthetics agents–Volatile anesthetic agents have several contradictory effects on microcirculatory flow. They decrease flow in the microcirculation by reducing arterial perfusion pressure and depressing myocardial contractility. At the same time these agents can increase flow in the microcirculation by inducing a vasodilatory response118. As a result, clinically useful concentrations of volatile agents will often produce systemic hypotension and decrease regional tissue perfusion in a tissue and agent specific manner119. Muscle perfusion under anesthesia with volatile agents is better maintained in young subjects than in aged subjects120. Not all effects of inhalation anesthesia are detrimental to tissue repair (Figure 5). Volatile anesthetics protect against ischemia-reperfusion injury of several organs (heart121, liver122, kidney123 and potentially others) by reducing necrosis and inflammation124. Several lines of evidence suggest that inhalation anesthetics exert their effects by affecting the microcirculation and influencing subsequent angiogenesis. For example, exposure to volatile anesthetics stimulates growth and proliferation of endothelial progenitor cells125. Volatile anesthetics, at clinically relevant doses, block transcription factor Hypoxia-inducible factor-1 activity and expression of its downstream target genes. Hypoxia-inducible factor-1 is a transcriptional regulator of VEGF expression126 and mediates angiogenic responses to reduced oxygen availability127. When renal proximal tubule cells were exposed to volatile anesthetics for sixteen hours there was increased production and release of TGF-1, a potent stimulator of extracellular matrix synthesis, into the cell culture media. The role of TGF-1 in the protective effect of volatile agents on ischemic injury to the kidney was specifically demonstrated in vivo – mice heterozygous for TGF-1 (TGF-1) were not protected from ischemia reperfusion injury by sevoflurane and a neutralizing TGF-1 antibody blockedAnesthesiology. Author manuscript; available in PMC 2015 March 01.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptBentov and ReedPagerenal protection with sevoflurane in TGF-1 mice128. Despite the data above, it is worth noting that volatile anesthetic agents differ in their effects on the microcirculation with respect to specific agents (desflurane versus isoflurane versus sevoflurane), target organs (heart versus kidney versus splanchnic), and clinical states (healthy versus sepsis versus hemorrhagic states)129. Consequently, we cannot make meaningful recommendations regarding volatile anesthetics and wound healing outcomes. III.

T pseudo-selfexchange reactions of TEMPO and related alkyl aminoxyl radicals have

T pseudo-selfexchange reactions of TEMPO and related alkyl aminoxyl radicals have been found to involve significant hydrogen tunneling (as do some cross reactions), in contrast to the related reactions of aryl aminoxyl radicals.74,75 The BDFE and BDE of TEMPOH will serve as benchmarks for some of the following discussion. We have CPI-455 web recently critically evaluated the BDE and BDFE of TEMPOH in MeCN and C6H6 solvents, using both reported calorimetric measurements76 and E?and pKa data (Table 3).40 The calorimetric measurements, for diphenylhydrazine + 2 TEMPO azobenzene + 2 TEMPOH, were reinterpreted using the recently revised heat of formation of azobenzene.77 The other noteworthy redox reaction of TEMPO is its oxidation to the corresponding nitrosonium cation. The nitrosonium cation has received attention for its superoxide dismutase-type BMS-791325MedChemExpress Beclabuvir reactivity78 and catalytic alcohol oxidations,79 both of which can be described as PCET processes. In water E?TEMPO?+) = 0.74 V (vs. NHE),80,81 and in MeCN E?TEMPO?+) = 0.61 V82 (vs. SCE; better: 0.24 V vs. Cp2Fe+/0 33). Several 4-substituted derivatives of TEMPO have been investigated, including 4-oxo-, 4methoxy-, Mirogabalin web 4-amino-, and 4-hydroxy-TEMPO. Bond strengths for these and other aminoxyls in hexane have been reported by Malievskii et al. from kinetic and equilibrium measurements,83 but little acidity or redox potential data are available for these other TEMPO derivatives. As noted above, the TEMPO(?H) 1H+/1e- couple is an excellent example of a PCET reagent that favors GGTI298 chemical information concerted H?transfer over stepwise ET-PT or PT-ET pathways. TEMPOH (pKa = 41 in MeCN) is a very poor acid and TEMPO (pKa -4) is a poor base. Likewise, it is difficult to oxidize TEMPOH to TEMPOH? (Ep,a = 0.71 V vs. Cp2Fe+/0) and quite difficult to reduce TEMPO to TEMPO- (Ep,c = -1.95 V). These data indicate that under typical conditions, TEMPO- and TEMPOH?, the species at the top right and bottom left of the TEMPO square scheme (see Scheme 4), are high-energy species. The preference for concerted transfer of H?in reactions of TEMPO and TEMPOH can be illustrated by examining the energetics for the different pathways for the TEMPOH + TEMPO self exchange reaction (Scheme 7). HAT from TEMPOH to TEMPO has G?= 0 because it is a degenerate process. In MeCN, initial PT from TEMPOH to TEMPO gives TEMPO- + TEMPOH?. This reaction has an equilibrium constant of 10-45 based on the pKas of 41 and -4 respectively (Table 3), indicating a very unfavorable free energy, G T +60 kcal mol-1. Initial ET from TEMPOH to TEMPO is uphill by the same amount ( 2.7 V from the redox potentials). Note that for the unique case of a self-exchange reaction XH + X, these two values must be the same, because initial PT and ET both make the same intermediate state, XH+ + X-.84 Thus, there is a very large (60 kcal mol-1) bias favoring concerted transfer of e- and H+. The self-exchange reaction occurs readily, proceeding on the stopped flow timescale with an Eyring barrier G = 16.5 kcal mol-1 in MeCN.38,74 On this basis, the self-exchange cannot be proceeding through an intermediate state that is 60 kcal mol-1 above the ground state; the two particles must transfer together. This type of thermochemical argument, probably first applied to PCET by Meyer and coworkers,1 is quite powerful and is discussed in more detail for cross reactions in Section 6.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011.T pseudo-selfexchange reactions of TEMPO and related alkyl aminoxyl radicals have been found to involve significant hydrogen tunneling (as do some cross reactions), in contrast to the related reactions of aryl aminoxyl radicals.74,75 The BDFE and BDE of TEMPOH will serve as benchmarks for some of the following discussion. We have recently critically evaluated the BDE and BDFE of TEMPOH in MeCN and C6H6 solvents, using both reported calorimetric measurements76 and E?and pKa data (Table 3).40 The calorimetric measurements, for diphenylhydrazine + 2 TEMPO azobenzene + 2 TEMPOH, were reinterpreted using the recently revised heat of formation of azobenzene.77 The other noteworthy redox reaction of TEMPO is its oxidation to the corresponding nitrosonium cation. The nitrosonium cation has received attention for its superoxide dismutase-type reactivity78 and catalytic alcohol oxidations,79 both of which can be described as PCET processes. In water E?TEMPO?+) = 0.74 V (vs. NHE),80,81 and in MeCN E?TEMPO?+) = 0.61 V82 (vs. SCE; better: 0.24 V vs. Cp2Fe+/0 33). Several 4-substituted derivatives of TEMPO have been investigated, including 4-oxo-, 4methoxy-, 4-amino-, and 4-hydroxy-TEMPO. Bond strengths for these and other aminoxyls in hexane have been reported by Malievskii et al. from kinetic and equilibrium measurements,83 but little acidity or redox potential data are available for these other TEMPO derivatives. As noted above, the TEMPO(?H) 1H+/1e- couple is an excellent example of a PCET reagent that favors concerted H?transfer over stepwise ET-PT or PT-ET pathways. TEMPOH (pKa = 41 in MeCN) is a very poor acid and TEMPO (pKa -4) is a poor base. Likewise, it is difficult to oxidize TEMPOH to TEMPOH? (Ep,a = 0.71 V vs. Cp2Fe+/0) and quite difficult to reduce TEMPO to TEMPO- (Ep,c = -1.95 V). These data indicate that under typical conditions, TEMPO- and TEMPOH?, the species at the top right and bottom left of the TEMPO square scheme (see Scheme 4), are high-energy species. The preference for concerted transfer of H?in reactions of TEMPO and TEMPOH can be illustrated by examining the energetics for the different pathways for the TEMPOH + TEMPO self exchange reaction (Scheme 7). HAT from TEMPOH to TEMPO has G?= 0 because it is a degenerate process. In MeCN, initial PT from TEMPOH to TEMPO gives TEMPO- + TEMPOH?. This reaction has an equilibrium constant of 10-45 based on the pKas of 41 and -4 respectively (Table 3), indicating a very unfavorable free energy, G T +60 kcal mol-1. Initial ET from TEMPOH to TEMPO is uphill by the same amount ( 2.7 V from the redox potentials). Note that for the unique case of a self-exchange reaction XH + X, these two values must be the same, because initial PT and ET both make the same intermediate state, XH+ + X-.84 Thus, there is a very large (60 kcal mol-1) bias favoring concerted transfer of e- and H+. The self-exchange reaction occurs readily, proceeding on the stopped flow timescale with an Eyring barrier G = 16.5 kcal mol-1 in MeCN.38,74 On this basis, the self-exchange cannot be proceeding through an intermediate state that is 60 kcal mol-1 above the ground state; the two particles must transfer together. This type of thermochemical argument, probably first applied to PCET by Meyer and coworkers,1 is quite powerful and is discussed in more detail for cross reactions in Section 6.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011.T pseudo-selfexchange reactions of TEMPO and related alkyl aminoxyl radicals have been found to involve significant hydrogen tunneling (as do some cross reactions), in contrast to the related reactions of aryl aminoxyl radicals.74,75 The BDFE and BDE of TEMPOH will serve as benchmarks for some of the following discussion. We have recently critically evaluated the BDE and BDFE of TEMPOH in MeCN and C6H6 solvents, using both reported calorimetric measurements76 and E?and pKa data (Table 3).40 The calorimetric measurements, for diphenylhydrazine + 2 TEMPO azobenzene + 2 TEMPOH, were reinterpreted using the recently revised heat of formation of azobenzene.77 The other noteworthy redox reaction of TEMPO is its oxidation to the corresponding nitrosonium cation. The nitrosonium cation has received attention for its superoxide dismutase-type reactivity78 and catalytic alcohol oxidations,79 both of which can be described as PCET processes. In water E?TEMPO?+) = 0.74 V (vs. NHE),80,81 and in MeCN E?TEMPO?+) = 0.61 V82 (vs. SCE; better: 0.24 V vs. Cp2Fe+/0 33). Several 4-substituted derivatives of TEMPO have been investigated, including 4-oxo-, 4methoxy-, 4-amino-, and 4-hydroxy-TEMPO. Bond strengths for these and other aminoxyls in hexane have been reported by Malievskii et al. from kinetic and equilibrium measurements,83 but little acidity or redox potential data are available for these other TEMPO derivatives. As noted above, the TEMPO(?H) 1H+/1e- couple is an excellent example of a PCET reagent that favors concerted H?transfer over stepwise ET-PT or PT-ET pathways. TEMPOH (pKa = 41 in MeCN) is a very poor acid and TEMPO (pKa -4) is a poor base. Likewise, it is difficult to oxidize TEMPOH to TEMPOH? (Ep,a = 0.71 V vs. Cp2Fe+/0) and quite difficult to reduce TEMPO to TEMPO- (Ep,c = -1.95 V). These data indicate that under typical conditions, TEMPO- and TEMPOH?, the species at the top right and bottom left of the TEMPO square scheme (see Scheme 4), are high-energy species. The preference for concerted transfer of H?in reactions of TEMPO and TEMPOH can be illustrated by examining the energetics for the different pathways for the TEMPOH + TEMPO self exchange reaction (Scheme 7). HAT from TEMPOH to TEMPO has G?= 0 because it is a degenerate process. In MeCN, initial PT from TEMPOH to TEMPO gives TEMPO- + TEMPOH?. This reaction has an equilibrium constant of 10-45 based on the pKas of 41 and -4 respectively (Table 3), indicating a very unfavorable free energy, G T +60 kcal mol-1. Initial ET from TEMPOH to TEMPO is uphill by the same amount ( 2.7 V from the redox potentials). Note that for the unique case of a self-exchange reaction XH + X, these two values must be the same, because initial PT and ET both make the same intermediate state, XH+ + X-.84 Thus, there is a very large (60 kcal mol-1) bias favoring concerted transfer of e- and H+. The self-exchange reaction occurs readily, proceeding on the stopped flow timescale with an Eyring barrier G = 16.5 kcal mol-1 in MeCN.38,74 On this basis, the self-exchange cannot be proceeding through an intermediate state that is 60 kcal mol-1 above the ground state; the two particles must transfer together. This type of thermochemical argument, probably first applied to PCET by Meyer and coworkers,1 is quite powerful and is discussed in more detail for cross reactions in Section 6.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011.T pseudo-selfexchange reactions of TEMPO and related alkyl aminoxyl radicals have been found to involve significant hydrogen tunneling (as do some cross reactions), in contrast to the related reactions of aryl aminoxyl radicals.74,75 The BDFE and BDE of TEMPOH will serve as benchmarks for some of the following discussion. We have recently critically evaluated the BDE and BDFE of TEMPOH in MeCN and C6H6 solvents, using both reported calorimetric measurements76 and E?and pKa data (Table 3).40 The calorimetric measurements, for diphenylhydrazine + 2 TEMPO azobenzene + 2 TEMPOH, were reinterpreted using the recently revised heat of formation of azobenzene.77 The other noteworthy redox reaction of TEMPO is its oxidation to the corresponding nitrosonium cation. The nitrosonium cation has received attention for its superoxide dismutase-type reactivity78 and catalytic alcohol oxidations,79 both of which can be described as PCET processes. In water E?TEMPO?+) = 0.74 V (vs. NHE),80,81 and in MeCN E?TEMPO?+) = 0.61 V82 (vs. SCE; better: 0.24 V vs. Cp2Fe+/0 33). Several 4-substituted derivatives of TEMPO have been investigated, including 4-oxo-, 4methoxy-, 4-amino-, and 4-hydroxy-TEMPO. Bond strengths for these and other aminoxyls in hexane have been reported by Malievskii et al. from kinetic and equilibrium measurements,83 but little acidity or redox potential data are available for these other TEMPO derivatives. As noted above, the TEMPO(?H) 1H+/1e- couple is an excellent example of a PCET reagent that favors concerted H?transfer over stepwise ET-PT or PT-ET pathways. TEMPOH (pKa = 41 in MeCN) is a very poor acid and TEMPO (pKa -4) is a poor base. Likewise, it is difficult to oxidize TEMPOH to TEMPOH? (Ep,a = 0.71 V vs. Cp2Fe+/0) and quite difficult to reduce TEMPO to TEMPO- (Ep,c = -1.95 V). These data indicate that under typical conditions, TEMPO- and TEMPOH?, the species at the top right and bottom left of the TEMPO square scheme (see Scheme 4), are high-energy species. The preference for concerted transfer of H?in reactions of TEMPO and TEMPOH can be illustrated by examining the energetics for the different pathways for the TEMPOH + TEMPO self exchange reaction (Scheme 7). HAT from TEMPOH to TEMPO has G?= 0 because it is a degenerate process. In MeCN, initial PT from TEMPOH to TEMPO gives TEMPO- + TEMPOH?. This reaction has an equilibrium constant of 10-45 based on the pKas of 41 and -4 respectively (Table 3), indicating a very unfavorable free energy, G T +60 kcal mol-1. Initial ET from TEMPOH to TEMPO is uphill by the same amount ( 2.7 V from the redox potentials). Note that for the unique case of a self-exchange reaction XH + X, these two values must be the same, because initial PT and ET both make the same intermediate state, XH+ + X-.84 Thus, there is a very large (60 kcal mol-1) bias favoring concerted transfer of e- and H+. The self-exchange reaction occurs readily, proceeding on the stopped flow timescale with an Eyring barrier G = 16.5 kcal mol-1 in MeCN.38,74 On this basis, the self-exchange cannot be proceeding through an intermediate state that is 60 kcal mol-1 above the ground state; the two particles must transfer together. This type of thermochemical argument, probably first applied to PCET by Meyer and coworkers,1 is quite powerful and is discussed in more detail for cross reactions in Section 6.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011.

S areola obscured by propodeum sculpture, but still evident as an

S areola obscured by propodeum sculpture, but still evident as an impression) or, very rarely, without any definition of an areola; b) Vannal lobe margin strongly concave to almost straight, and lacking setae at midlength (if some setae are present, they are small and sparsely distributed); c) posterior edge of the scutellar disc smooth; d) vein cu-a in the hind wing not Linaprazan cost sinuate. There are other useful characters to distinguish the genus (e.g. see Mason 1981, Whitfield 1997); but the four detailed above serve well to separate the Apanteles sensu stricto described here from Choeras (character a), from Dolichogenidea (character b), from Exoryza (character b), from Iconella (character d), and from Illidops (character c). A total of 23 Apanteles species were previously known from Mesoamerica (Yu et al. 2012, Smith et al. 2013). After studying the type material for these taxa, 19 are retained in Apanteles sensu stricto and treated in this paper, while four species are transferred to other Microgastrinae genera. The status of the Mesoamerican species Apanteles albinervis (Cameron 1904) is revised, and one European species that is involved in a secondary homonym with the former is transferred to Iconella. All of these nomenclatorial acts are detailed below. When the 186 new species from ACG described in this paper are included, the Apanteles fauna of Mesoamerica comprises 205 species, or about 10 times more species than previously known from that region. There was only one described species recorded from Costa Rica, 19 from Mesoamerica, 86 from the Neotropical region, and 1010 worldwide (Yu et al. 2012). This study emphasizes how much is still unknown about the diversity of parasitoid wasps in general, and Microgastrinae in particular (e.g., Rodriguez et al. 2012). It is unlikely that ACG contains 20 of the species of a global genus as widely distributed and diverse as Apanteles. A more logical explanation is that, whenever other regions are as comprehensively studied, many more undescribed species of Apanteles will be revealed. Even for ACG we are far from completing the inventory of Apanteles. We are aware of another 19 species (which would represent an additional 10 of increase for ACG), which we had to exclude because the available specimens were in poor condition and/or were only represented by males (in most cases Microgastrinae male specimens cannot be taxonomically dealt with, except through their DNA barcodes, or by inference through membership in a LLY-507 side effects presumed sib group containing females, or reared from only one caterpillar). Those species are not described in this paper, although some of their interim names are provided here, for future reference, Apanteles Janzen11, Apanteles Janzen16, Apanteles Janzen34, Apanteles Rodriguez50, Apanteles Rodriguez74, Apanteles Rodriguez75, Apanteles Rodriguez79, Apanteles Rodriguez109, Apanteles Rodriguez121, Apanteles Rodriguez127, Apan-Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)teles Rodriguez128, Apanteles Rodriguez138, Apanteles Rodriguez143, Apanteles Rodriguez149, Apanteles Rodriguez161, Apanteles Rodriguez185, Apanteles Rodriguez200, Apanteles Rodriguez216, and Apanteles Rodriguez250. Full details of these presumed species and many more can be found in the ACG database online (http:// janzen.sas.upenn.edu/caterpillars/database.lasso). We will describe these species in subsequent papers on the ACG Microgastrinae.Species formerly described as Apanteles but here excluded from the.S areola obscured by propodeum sculpture, but still evident as an impression) or, very rarely, without any definition of an areola; b) Vannal lobe margin strongly concave to almost straight, and lacking setae at midlength (if some setae are present, they are small and sparsely distributed); c) posterior edge of the scutellar disc smooth; d) vein cu-a in the hind wing not sinuate. There are other useful characters to distinguish the genus (e.g. see Mason 1981, Whitfield 1997); but the four detailed above serve well to separate the Apanteles sensu stricto described here from Choeras (character a), from Dolichogenidea (character b), from Exoryza (character b), from Iconella (character d), and from Illidops (character c). A total of 23 Apanteles species were previously known from Mesoamerica (Yu et al. 2012, Smith et al. 2013). After studying the type material for these taxa, 19 are retained in Apanteles sensu stricto and treated in this paper, while four species are transferred to other Microgastrinae genera. The status of the Mesoamerican species Apanteles albinervis (Cameron 1904) is revised, and one European species that is involved in a secondary homonym with the former is transferred to Iconella. All of these nomenclatorial acts are detailed below. When the 186 new species from ACG described in this paper are included, the Apanteles fauna of Mesoamerica comprises 205 species, or about 10 times more species than previously known from that region. There was only one described species recorded from Costa Rica, 19 from Mesoamerica, 86 from the Neotropical region, and 1010 worldwide (Yu et al. 2012). This study emphasizes how much is still unknown about the diversity of parasitoid wasps in general, and Microgastrinae in particular (e.g., Rodriguez et al. 2012). It is unlikely that ACG contains 20 of the species of a global genus as widely distributed and diverse as Apanteles. A more logical explanation is that, whenever other regions are as comprehensively studied, many more undescribed species of Apanteles will be revealed. Even for ACG we are far from completing the inventory of Apanteles. We are aware of another 19 species (which would represent an additional 10 of increase for ACG), which we had to exclude because the available specimens were in poor condition and/or were only represented by males (in most cases Microgastrinae male specimens cannot be taxonomically dealt with, except through their DNA barcodes, or by inference through membership in a presumed sib group containing females, or reared from only one caterpillar). Those species are not described in this paper, although some of their interim names are provided here, for future reference, Apanteles Janzen11, Apanteles Janzen16, Apanteles Janzen34, Apanteles Rodriguez50, Apanteles Rodriguez74, Apanteles Rodriguez75, Apanteles Rodriguez79, Apanteles Rodriguez109, Apanteles Rodriguez121, Apanteles Rodriguez127, Apan-Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)teles Rodriguez128, Apanteles Rodriguez138, Apanteles Rodriguez143, Apanteles Rodriguez149, Apanteles Rodriguez161, Apanteles Rodriguez185, Apanteles Rodriguez200, Apanteles Rodriguez216, and Apanteles Rodriguez250. Full details of these presumed species and many more can be found in the ACG database online (http:// janzen.sas.upenn.edu/caterpillars/database.lasso). We will describe these species in subsequent papers on the ACG Microgastrinae.Species formerly described as Apanteles but here excluded from the.

Rld context could be dangerous, expensive, or even impossible [46]. Computer-generated content

Rld context could be dangerous, expensive, or even impossible [46]. Computer-generated content, such as sound, graphics, 3D, video, or text, shows learners an indirect view of surroundings and enhances learners’ different senses to achieve the learning objectives. In these environments, learning activities are added, which will help medical learners to recognize and build their personal paradigm as they develop skills, gain insights, and determine the dispositions that are essential for translating what they learn into action. Each mixed environment in MARE has its own focus on different learning activities, and the environments should complement and reinforce one another.Personal ParadigmThe personal paradigm is compiled from the frames of reference that shape learners’ beliefs regarding guiding JWH-133 supplier action in transformative learning theory. The personal paradigm combines the individual’s mind-sets, habits, and meaning perspectives,http://mededu.jmir.org/2015/2/e10/and JWH-133MedChemExpress JWH-133 encompasses cognitive, conative, and affective components. This paradigm is affected by sociolinguistics, moral and ethical values, learning styles, religious beliefs, psychological heath, and aesthetic preferences [43], and is developed through the learners’ learning and/or practice experience. Problematic frames of reference can be caused by poor teaching, disjointed practice,JMIR Medical Education 2015 | vol. 1 | iss. 2 | e10 | p.9 (page number not for citation purposes)XSL?FORenderXJMIR MEDICAL EDUCATION bad example by colleagues, patient pressure, and salesmanship [47].Zhu et al for easy understanding. Attitudes within each level will be surveyed through an attitude questionnaire instrument.Learning Environment, Assets, and ActivitiesThe learning environment provides the conditions and external stimuli that facilitate learning and transform the learners’ paradigms. Learning assets provide the content for learning [48]. Learning assets are composed of different media forms, such as text, sound, and video; various media can be used in MARE to create different learning environments and realize the valuable functions of different media [49]. MARE mixes real clinical environments and virtual environments in a learning environment within which learners feel, think, watch, and act. Real clinical environments are an immediate context in which learners connect with the learning and practice. These environments include physical environments and social environments. As expected by situation learning theory [39], the clinical environments provide the anchor and scaffold in which learning is encouraged. The virtual environment is useful for learners who learn in different ways and transforms the problematic frames of reference in their personal paradigms. These types of environments conform to create safe environments, in which learners experience learning theories including transformative learning theory [42]. Learning activities are the approach by which learners obtain meaning from learning material, context, and other people in the learning environment. The three learning theories suggest various learning activities, as seen in Table 1. Although an individual’s learning style preferences may be inclined toward specific activities, using diverse learning activities is effective for all learning styles [42].Knowledge LevelKnowledge-level expectations for GPs regarding the rational use of antibiotics are shown in Table 1. When GPs use MARE as a tool for evaluating knowledge, they ca.Rld context could be dangerous, expensive, or even impossible [46]. Computer-generated content, such as sound, graphics, 3D, video, or text, shows learners an indirect view of surroundings and enhances learners’ different senses to achieve the learning objectives. In these environments, learning activities are added, which will help medical learners to recognize and build their personal paradigm as they develop skills, gain insights, and determine the dispositions that are essential for translating what they learn into action. Each mixed environment in MARE has its own focus on different learning activities, and the environments should complement and reinforce one another.Personal ParadigmThe personal paradigm is compiled from the frames of reference that shape learners’ beliefs regarding guiding action in transformative learning theory. The personal paradigm combines the individual’s mind-sets, habits, and meaning perspectives,http://mededu.jmir.org/2015/2/e10/and encompasses cognitive, conative, and affective components. This paradigm is affected by sociolinguistics, moral and ethical values, learning styles, religious beliefs, psychological heath, and aesthetic preferences [43], and is developed through the learners’ learning and/or practice experience. Problematic frames of reference can be caused by poor teaching, disjointed practice,JMIR Medical Education 2015 | vol. 1 | iss. 2 | e10 | p.9 (page number not for citation purposes)XSL?FORenderXJMIR MEDICAL EDUCATION bad example by colleagues, patient pressure, and salesmanship [47].Zhu et al for easy understanding. Attitudes within each level will be surveyed through an attitude questionnaire instrument.Learning Environment, Assets, and ActivitiesThe learning environment provides the conditions and external stimuli that facilitate learning and transform the learners’ paradigms. Learning assets provide the content for learning [48]. Learning assets are composed of different media forms, such as text, sound, and video; various media can be used in MARE to create different learning environments and realize the valuable functions of different media [49]. MARE mixes real clinical environments and virtual environments in a learning environment within which learners feel, think, watch, and act. Real clinical environments are an immediate context in which learners connect with the learning and practice. These environments include physical environments and social environments. As expected by situation learning theory [39], the clinical environments provide the anchor and scaffold in which learning is encouraged. The virtual environment is useful for learners who learn in different ways and transforms the problematic frames of reference in their personal paradigms. These types of environments conform to create safe environments, in which learners experience learning theories including transformative learning theory [42]. Learning activities are the approach by which learners obtain meaning from learning material, context, and other people in the learning environment. The three learning theories suggest various learning activities, as seen in Table 1. Although an individual’s learning style preferences may be inclined toward specific activities, using diverse learning activities is effective for all learning styles [42].Knowledge LevelKnowledge-level expectations for GPs regarding the rational use of antibiotics are shown in Table 1. When GPs use MARE as a tool for evaluating knowledge, they ca.

Sequence described in the E26 27 avian erythroblastosis virus (E26 Transformation-specific Sequence

Sequence described in the E26 27 avian erythroblastosis virus (E26 Transformation-specific Sequence). Studies in mutant mice have Pan-RAS-IN-1 chemical information demonstrated that ETS-1 knockout animals have a lower number of glomeruli, 28 and among the existing glomeruli, a higher number are immature, highlighting the 29 31 important role of ETS-1 in the regulation of normal kidney development. ?The transcriptional activity of ETS-1 is PM01183 web modulated through post-translational modifications. 32 Phosphorylation of threonine-38 increases the transcriptional activity of ETS-1 while calmodulin-dependent kinase II inhibits DNA binding through serine phosphorylation of 33 ETS-1 inhibitory domains. ETS-1 is also regulated through nuclear transport via specific nuclear localization sequences that facilitate the movement of ETS-1 from the cytoplasm 34 into the nucleus. The renal expression of ETS-1 is increased in a variety of models of renal injury. The antiThy1 model of glomerulonephritis is associated with a 4-fold increase in ETS-1 expression predominantly in the glomerular mesangium and at a lesser degree in podocytes and the 35 glomerular endothelium. In rats with antiglomerular basement nduced glomerulonephritis, there is also increased upregulation of ETS-1 in the glomeruli and in the 36 interstitium, and in an ischemic model of acute renal failure, the tubular expression of ETS-1 is increased and associated with augmented expression of cyclin D, suggesting a role 37 for ETS-1 in the control of tubular regeneration in acute kidney injury. In previous studies, we also demonstrated that Ang II increases the cortical expression of ETS-1 in SpragueDawley rats and that knockdown of ETS-1 reduces Ang II-stimulated fibronectin production 38 in rat mesangial cells. In other studies, we demonstrated that Ang II increases the glomerular expression of ETS-1 in mice and that blockade of ETS-1 using a specific DN 13 reduces proteinuria, inflammation, and fibrosis induced by Ang II. Importantly, in these studies, ETS-1 blockade did not reduce blood pressure, suggesting that hemodynamic effects did not mediate the beneficial actions of ETS-1 blockade. In the present studies, we have demonstrated increased glomerular expression of ETS-1 in hypertensive Dahl/Rapp salt-sensitive rats, a paradigm of salt-sensitive hypertension in humans. We demonstrated that hypertensive Dahl/Rapp salt-sensitive rats have a significant increase in the expression of the phosphorylated (T38) form of ETS-1 without significant changes in the expression of total ETS-1. Although we did not observe changes in the expression of total ETS-1, we cannot rule out that changes in the expression of total ETS-Hypertension. Author manuscript; available in PMC 2016 June 08.Feng et al.Pagemay occur at other time points. Using colocalization methods, we demonstrated that the expression of ETS-1 is mostly glomerular and predominantly expressed in the glomerular epithelium and to a lesser degree in the glomerular endothelium. Several studies have demonstrated that DS rats when fed a high-salt diet and made hypertensive have increased local activation of the RAS, characterized by sustained levels of 14 Ang II, increased levels of angiotensinogen, and increased expression of the AT1 receptor. In addition, as others and we have shown, salt-sensitive hypertension is associated with 2 reduced nitric oxide bioavailability and increased reactive oxygen species production. ,39,40 In support of the role for increased RAS activation in s.Sequence described in the E26 27 avian erythroblastosis virus (E26 Transformation-specific Sequence). Studies in mutant mice have demonstrated that ETS-1 knockout animals have a lower number of glomeruli, 28 and among the existing glomeruli, a higher number are immature, highlighting the 29 31 important role of ETS-1 in the regulation of normal kidney development. ?The transcriptional activity of ETS-1 is modulated through post-translational modifications. 32 Phosphorylation of threonine-38 increases the transcriptional activity of ETS-1 while calmodulin-dependent kinase II inhibits DNA binding through serine phosphorylation of 33 ETS-1 inhibitory domains. ETS-1 is also regulated through nuclear transport via specific nuclear localization sequences that facilitate the movement of ETS-1 from the cytoplasm 34 into the nucleus. The renal expression of ETS-1 is increased in a variety of models of renal injury. The antiThy1 model of glomerulonephritis is associated with a 4-fold increase in ETS-1 expression predominantly in the glomerular mesangium and at a lesser degree in podocytes and the 35 glomerular endothelium. In rats with antiglomerular basement nduced glomerulonephritis, there is also increased upregulation of ETS-1 in the glomeruli and in the 36 interstitium, and in an ischemic model of acute renal failure, the tubular expression of ETS-1 is increased and associated with augmented expression of cyclin D, suggesting a role 37 for ETS-1 in the control of tubular regeneration in acute kidney injury. In previous studies, we also demonstrated that Ang II increases the cortical expression of ETS-1 in SpragueDawley rats and that knockdown of ETS-1 reduces Ang II-stimulated fibronectin production 38 in rat mesangial cells. In other studies, we demonstrated that Ang II increases the glomerular expression of ETS-1 in mice and that blockade of ETS-1 using a specific DN 13 reduces proteinuria, inflammation, and fibrosis induced by Ang II. Importantly, in these studies, ETS-1 blockade did not reduce blood pressure, suggesting that hemodynamic effects did not mediate the beneficial actions of ETS-1 blockade. In the present studies, we have demonstrated increased glomerular expression of ETS-1 in hypertensive Dahl/Rapp salt-sensitive rats, a paradigm of salt-sensitive hypertension in humans. We demonstrated that hypertensive Dahl/Rapp salt-sensitive rats have a significant increase in the expression of the phosphorylated (T38) form of ETS-1 without significant changes in the expression of total ETS-1. Although we did not observe changes in the expression of total ETS-1, we cannot rule out that changes in the expression of total ETS-Hypertension. Author manuscript; available in PMC 2016 June 08.Feng et al.Pagemay occur at other time points. Using colocalization methods, we demonstrated that the expression of ETS-1 is mostly glomerular and predominantly expressed in the glomerular epithelium and to a lesser degree in the glomerular endothelium. Several studies have demonstrated that DS rats when fed a high-salt diet and made hypertensive have increased local activation of the RAS, characterized by sustained levels of 14 Ang II, increased levels of angiotensinogen, and increased expression of the AT1 receptor. In addition, as others and we have shown, salt-sensitive hypertension is associated with 2 reduced nitric oxide bioavailability and increased reactive oxygen species production. ,39,40 In support of the role for increased RAS activation in s.

E the ways in which negotiations for the care of AIDS

E the ways in which negotiations for the care of AIDS orphans utilizes the cultural logics of bridewealth and patrilineality in order to justify a range of configurations of care.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSituating caregiving: fostering, migrant labour, and marriageLike many of the grandmothers I spoke with, ‘M’e Matau lived with her own maternal grandmother from early childhood until she was 15 years old. She was sent by her parents to provide companionship and to assist her grandmother with household chores. Basotho like ‘M’e Matau use what they know about BQ-123 custom synthesis fostering from their own experiences and adapt it to accommodate shifting domestic arrangements stemming from the increase in the number of orphans. While this recent increase is perhaps more dramatic owing to the severity and scale of the AIDS pandemic, caregiving practices, including child fostering, have always been in flux, shifting in response to historical and political-economic circumstances. In this section, I situate long-standing child fostering practices that serve as the basis for the contemporary movement of AIDS orphans, and trace the legal and historical processes that have impacted these practices, with a focus on migrant labour and marriage. Child fostering has been widely studied across the African continent (Bledsoe 1989; Goody 1982; Madhavan 2004; Renne 1993). It is typically characterized by the movement of children for a variety of purposes related to health, fertility, social responsibility, caregiving relationships, apprenticeship, and educational opportunities. Despite numerous characterizations of fostering as fundamentally reciprocal in nature (Bledsoe 1989), such practices are not always beneficial or voluntary. Several scholars have highlighted the role that poverty plays in the circulation of children, often transferring the productive contributions of children from one household to another (Goody 1982; Leinaweaver 2007; Schrauwers 1999). Thus, processes that shape social relationships are not always unambiguously positive, alliance-building strategies, but may also be necessitated by poverty, inequality, and disease. Child fostering has a long history in Lesotho as a regular strategy for sharing responsibility and supporting and connecting kin (Murray 1981; Page 1989). In Lesotho, HIV/AIDS has been a major Sodium lasalocid biological activity factor in changing fostering patterns, as it has elsewhere in sub-Saharan Africa. 4 Household migration has been an important coping strategy employed by children and families impacted by AIDS (Ansell van Blerk 2004). Although orphans are still predominantly cared for within the family, researchers worry that family and communitybased networks of care are becoming saturated (Abebe Aase 2007; Courtney buy Mangafodipir (trisodium) Iwaniec 2009; L. Townsend Dawes 2004). Others also note that increased pressure on caregivers has resulted in some children receiving inadequate care, as caregivers struggle to meet these children’s needs, whether financial (Ansell van Blerk 2004; Kidman, Petrow Heymann 2007) or emotional and psycho-social (Ansell Young 2004; Nyesigomwe 2005). The emergence and uncertainty of matrilocal care must be understood as embedded in a context4UNICEF (2010) Lasalocid (sodium) price estimates that there are 110,000?20,000 AIDS orphans in Lesotho; of these children, 12,000 are HIV-positive. J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagethat is constrained not only by AIDS and poverty but also by a varie.E the ways in which negotiations for the care of AIDS orphans utilizes the cultural logics of bridewealth and patrilineality in order to justify a range of configurations of care.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSituating caregiving: fostering, migrant labour, and marriageLike many of the grandmothers I spoke with, ‘M’e Matau lived with her own maternal grandmother from early childhood until she was 15 years old. She was sent by her parents to provide companionship and to assist her grandmother with household chores. Basotho like ‘M’e Matau use what they know about fostering from their own experiences and adapt it to accommodate shifting domestic arrangements stemming from the increase in the number of orphans. While this recent increase is perhaps more dramatic owing to the severity and scale of the AIDS pandemic, caregiving practices, including child fostering, have always been in flux, shifting in response to historical and political-economic circumstances. In this section, I situate long-standing child fostering practices that serve as the basis for the contemporary movement of AIDS orphans, and trace the legal and historical processes that have impacted these practices, with a focus on migrant labour and marriage. Child fostering has been widely studied across the African continent (Bledsoe 1989; Goody 1982; Madhavan 2004; Renne 1993). It is typically characterized by the movement of children for a variety of purposes related to health, fertility, social responsibility, caregiving relationships, apprenticeship, and educational opportunities. Despite numerous characterizations of fostering as fundamentally reciprocal in nature (Bledsoe 1989), such practices are not always beneficial or voluntary. Several scholars have highlighted the role that poverty plays in the circulation of children, often transferring the productive contributions of children from one household to another (Goody 1982; Leinaweaver 2007; Schrauwers 1999). Thus, processes that shape social relationships are not always unambiguously positive, alliance-building strategies, but may also be necessitated by poverty, inequality, and disease. Child fostering has a long history in Lesotho as a regular strategy for sharing responsibility and supporting and connecting kin (Murray 1981; Page 1989). In Lesotho, HIV/AIDS has been a major factor in changing fostering patterns, as it has elsewhere in sub-Saharan Africa. 4 Household migration has been an important coping strategy employed by children and families impacted by AIDS (Ansell van Blerk 2004). Although orphans are still predominantly cared for within the family, researchers worry that family and communitybased networks of care are becoming saturated (Abebe Aase 2007; Courtney Iwaniec 2009; L. Townsend Dawes 2004). Others also note that increased pressure on caregivers has resulted in some children receiving inadequate care, as caregivers struggle to meet these children’s needs, whether financial (Ansell van Blerk 2004; Kidman, Petrow Heymann 2007) or emotional and psycho-social (Ansell Young 2004; Nyesigomwe 2005). The emergence and uncertainty of matrilocal care must be understood as embedded in a context4UNICEF (2010) estimates that there are 110,000?20,000 AIDS orphans in Lesotho; of these children, 12,000 are HIV-positive. J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagethat is constrained not only by AIDS and poverty but also by a varie.E the ways in which negotiations for the care of AIDS orphans utilizes the cultural logics of bridewealth and patrilineality in order to justify a range of configurations of care.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSituating caregiving: fostering, migrant labour, and marriageLike many of the grandmothers I spoke with, ‘M’e Matau lived with her own maternal grandmother from early childhood until she was 15 years old. She was sent by her parents to provide companionship and to assist her grandmother with household chores. Basotho like ‘M’e Matau use what they know about fostering from their own experiences and adapt it to accommodate shifting domestic arrangements stemming from the increase in the number of orphans. While this recent increase is perhaps more dramatic owing to the severity and scale of the AIDS pandemic, caregiving practices, including child fostering, have always been in flux, shifting in response to historical and political-economic circumstances. In this section, I situate long-standing child fostering practices that serve as the basis for the contemporary movement of AIDS orphans, and trace the legal and historical processes that have impacted these practices, with a focus on migrant labour and marriage. Child fostering has been widely studied across the African continent (Bledsoe 1989; Goody 1982; Madhavan 2004; Renne 1993). It is typically characterized by the movement of children for a variety of purposes related to health, fertility, social responsibility, caregiving relationships, apprenticeship, and educational opportunities. Despite numerous characterizations of fostering as fundamentally reciprocal in nature (Bledsoe 1989), such practices are not always beneficial or voluntary. Several scholars have highlighted the role that poverty plays in the circulation of children, often transferring the productive contributions of children from one household to another (Goody 1982; Leinaweaver 2007; Schrauwers 1999). Thus, processes that shape social relationships are not always unambiguously positive, alliance-building strategies, but may also be necessitated by poverty, inequality, and disease. Child fostering has a long history in Lesotho as a regular strategy for sharing responsibility and supporting and connecting kin (Murray 1981; Page 1989). In Lesotho, HIV/AIDS has been a major factor in changing fostering patterns, as it has elsewhere in sub-Saharan Africa. 4 Household migration has been an important coping strategy employed by children and families impacted by AIDS (Ansell van Blerk 2004). Although orphans are still predominantly cared for within the family, researchers worry that family and communitybased networks of care are becoming saturated (Abebe Aase 2007; Courtney Iwaniec 2009; L. Townsend Dawes 2004). Others also note that increased pressure on caregivers has resulted in some children receiving inadequate care, as caregivers struggle to meet these children’s needs, whether financial (Ansell van Blerk 2004; Kidman, Petrow Heymann 2007) or emotional and psycho-social (Ansell Young 2004; Nyesigomwe 2005). The emergence and uncertainty of matrilocal care must be understood as embedded in a context4UNICEF (2010) estimates that there are 110,000?20,000 AIDS orphans in Lesotho; of these children, 12,000 are HIV-positive. J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagethat is constrained not only by AIDS and poverty but also by a varie.E the ways in which negotiations for the care of AIDS orphans utilizes the cultural logics of bridewealth and patrilineality in order to justify a range of configurations of care.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSituating caregiving: fostering, migrant labour, and marriageLike many of the grandmothers I spoke with, ‘M’e Matau lived with her own maternal grandmother from early childhood until she was 15 years old. She was sent by her parents to provide companionship and to assist her grandmother with household chores. Basotho like ‘M’e Matau use what they know about fostering from their own experiences and adapt it to accommodate shifting domestic arrangements stemming from the increase in the number of orphans. While this recent increase is perhaps more dramatic owing to the severity and scale of the AIDS pandemic, caregiving practices, including child fostering, have always been in flux, shifting in response to historical and political-economic circumstances. In this section, I situate long-standing child fostering practices that serve as the basis for the contemporary movement of AIDS orphans, and trace the legal and historical processes that have impacted these practices, with a focus on migrant labour and marriage. Child fostering has been widely studied across the African continent (Bledsoe 1989; Goody 1982; Madhavan 2004; Renne 1993). It is typically characterized by the movement of children for a variety of purposes related to health, fertility, social responsibility, caregiving relationships, apprenticeship, and educational opportunities. Despite numerous characterizations of fostering as fundamentally reciprocal in nature (Bledsoe 1989), such practices are not always beneficial or voluntary. Several scholars have highlighted the role that poverty plays in the circulation of children, often transferring the productive contributions of children from one household to another (Goody 1982; Leinaweaver 2007; Schrauwers 1999). Thus, processes that shape social relationships are not always unambiguously positive, alliance-building strategies, but may also be necessitated by poverty, inequality, and disease. Child fostering has a long history in Lesotho as a regular strategy for sharing responsibility and supporting and connecting kin (Murray 1981; Page 1989). In Lesotho, HIV/AIDS has been a major factor in changing fostering patterns, as it has elsewhere in sub-Saharan Africa. 4 Household migration has been an important coping strategy employed by children and families impacted by AIDS (Ansell van Blerk 2004). Although orphans are still predominantly cared for within the family, researchers worry that family and communitybased networks of care are becoming saturated (Abebe Aase 2007; Courtney Iwaniec 2009; L. Townsend Dawes 2004). Others also note that increased pressure on caregivers has resulted in some children receiving inadequate care, as caregivers struggle to meet these children’s needs, whether financial (Ansell van Blerk 2004; Kidman, Petrow Heymann 2007) or emotional and psycho-social (Ansell Young 2004; Nyesigomwe 2005). The emergence and uncertainty of matrilocal care must be understood as embedded in a context4UNICEF (2010) estimates that there are 110,000?20,000 AIDS orphans in Lesotho; of these children, 12,000 are HIV-positive. J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagethat is constrained not only by AIDS and poverty but also by a varie.

N a specific form.MethodsThe ORION statement for transparent reporting of

N a specific form.MethodsThe ORION statement for transparent reporting of intervention studies concerning healthcare-acquired infections was followed [36].SettingDelfos Medical Center is a private 200-bed hospital with teaching BUdR web Crotaline custom synthesis nursing activity, with about 12,000 admissions and 50,000 patient-days each year. Almost 90 of the rooms are single. There are eight medical-surgical wards and a polyvalent intensive care unit (ICU) with 11 beds attending nearly 500 patients each year. A Nosocomial Infection Control Unit (NICU) was created in 2002 as part of the Infection Committee, which is formed by a full-time specialist in epidemiology and infectious diseases and by an infection control nurse.Outcomes variablesThe primary outcome was HH compliance calculated by dividing the number of HH episodes by the number of potential opportunities. The data was stratified by type of indications, working areas and professional category. Our retrospective control data included three sessions of HH audits performed over a week in October 2007, January 2008 and April 2008.These audits were performed following a similar procedure as that used during the intervention period (with the exception that the moment “after touching surroundings” was not evaluated) and were conducted also by nosocomial infection control and nursing supervisors’ staff.Study DesignWe developed a “pre-post intervention” study through statistical comparison of HH performance at baseline and the two intervention phases. Furthermore, we performed prospective time series analysis through statistical process control (SPC) on HH during phase 2, alcohol hand rub solution (AHRs) consumption, and rate of healthcare-acquired MRSA colonization or infection (as detected by means of clinical samples only).The Ethics Committee from Delfos Medical Center approved conduct ofPLOS ONE | www.plosone.orgHospital Wide Hand Hygiene InterventionTable 1. Main characteristics of a 2 phase multifaceted hospital-wide hand hygiene intervention, Delfos Medical Center (2010?2011).Periods and data Preintervention period (March 2007 ecember 2009)Description Promotion of hand hygiene (HH) was performed but it was neither structured nor sustained on time. A limited HH campaign based on staff education, reminders (March 2007 ctober 2007) followed by limited six-month HH audit by direct observations (October 2007?April 2008) over a week (basal, and on month 3 and 6) was conducted. The alcohol hand rub solution (AHRs) was changed on June 2008 (SterilliumH gel, Bode Chemie, Hamburg, Germany); at this point, AHRs dispensers were located outside each room (corridor) and in the nursing carts. Isolation practices and HH promotion was reinforced during pandemic H1N1 threat (June2009-September 2009). Phase 2 (January 2011 ecember 2011) Continuous Quality Improvement (CQI) Promotion locally developed by Infection Control Unit and Supervisor’s Nursing Department. AHRs were placed at all patient beds in conventional wards while maintaining those at corridors. At this point the ratio AHRs dispensers/bed was 1.56 (340/217).Hospital Wide Intervention Phase 1 (January 2010 ecember 2010) Epidemiological context Catalonian Regional Campaign promoted by the “Alliance for Patient Safety” supported by WHO educational resources. AHRs were placed at all bedsides on high risk areas (Emergency Department and Intensive Care Unit). At this point the ratio AHRs dispensers/bed was 0.57 (123/217).1, Promotion of easy access to hand-rub solution.N a specific form.MethodsThe ORION statement for transparent reporting of intervention studies concerning healthcare-acquired infections was followed [36].SettingDelfos Medical Center is a private 200-bed hospital with teaching nursing activity, with about 12,000 admissions and 50,000 patient-days each year. Almost 90 of the rooms are single. There are eight medical-surgical wards and a polyvalent intensive care unit (ICU) with 11 beds attending nearly 500 patients each year. A Nosocomial Infection Control Unit (NICU) was created in 2002 as part of the Infection Committee, which is formed by a full-time specialist in epidemiology and infectious diseases and by an infection control nurse.Outcomes variablesThe primary outcome was HH compliance calculated by dividing the number of HH episodes by the number of potential opportunities. The data was stratified by type of indications, working areas and professional category. Our retrospective control data included three sessions of HH audits performed over a week in October 2007, January 2008 and April 2008.These audits were performed following a similar procedure as that used during the intervention period (with the exception that the moment “after touching surroundings” was not evaluated) and were conducted also by nosocomial infection control and nursing supervisors’ staff.Study DesignWe developed a “pre-post intervention” study through statistical comparison of HH performance at baseline and the two intervention phases. Furthermore, we performed prospective time series analysis through statistical process control (SPC) on HH during phase 2, alcohol hand rub solution (AHRs) consumption, and rate of healthcare-acquired MRSA colonization or infection (as detected by means of clinical samples only).The Ethics Committee from Delfos Medical Center approved conduct ofPLOS ONE | www.plosone.orgHospital Wide Hand Hygiene InterventionTable 1. Main characteristics of a 2 phase multifaceted hospital-wide hand hygiene intervention, Delfos Medical Center (2010?2011).Periods and data Preintervention period (March 2007 ecember 2009)Description Promotion of hand hygiene (HH) was performed but it was neither structured nor sustained on time. A limited HH campaign based on staff education, reminders (March 2007 ctober 2007) followed by limited six-month HH audit by direct observations (October 2007?April 2008) over a week (basal, and on month 3 and 6) was conducted. The alcohol hand rub solution (AHRs) was changed on June 2008 (SterilliumH gel, Bode Chemie, Hamburg, Germany); at this point, AHRs dispensers were located outside each room (corridor) and in the nursing carts. Isolation practices and HH promotion was reinforced during pandemic H1N1 threat (June2009-September 2009). Phase 2 (January 2011 ecember 2011) Continuous Quality Improvement (CQI) Promotion locally developed by Infection Control Unit and Supervisor’s Nursing Department. AHRs were placed at all patient beds in conventional wards while maintaining those at corridors. At this point the ratio AHRs dispensers/bed was 1.56 (340/217).Hospital Wide Intervention Phase 1 (January 2010 ecember 2010) Epidemiological context Catalonian Regional Campaign promoted by the “Alliance for Patient Safety” supported by WHO educational resources. AHRs were placed at all bedsides on high risk areas (Emergency Department and Intensive Care Unit). At this point the ratio AHRs dispensers/bed was 0.57 (123/217).1, Promotion of easy access to hand-rub solution.

Be good for a group discussion. . . just because I think time

Be good for a group discussion. . . just because I think time wise I think during clinic, it would be very lengthy. They would all want to try it (the order Thonzonium (bromide) demonstration with equipment). (Physician) For any integration to occur at the physician level, a paradigm shift in role may need to occur, as well as additional time for visits. The challenges are really more of a time factor because you’re trying to do it during clinic hours when other patients are waiting to be seen. And it seems like the time flies when you’re in the room with a patient. I don’t know how people see patients in 10 min. (Physician) The time barrier also seemed to be commonly linked to the frustration with other pressing responsibilities, such as paperwork, which interfere with providing more extensive clinical care services. This may be of particular concern in a publicly-funded clinic, whose paperwork requirements and grant writing are often completed by clinical leadership, and require time away from patients to complete. Whether it’s a form to go to the dentist or whatever it is you need, we take care of it, so it isn’t the actual hands on with the patient. A lot of times, it’s the paperwork that takes you a little while to get done. . . Like 30 percent of the time I’m actually taking care of the patient, and 70 percent, I’m taking care of all the paperwork needs that they have. (Physician)Carlberg-Racich (2016), PeerJ, DOI 10.7717/peerj.16/Despite the time barrier, the advanced practice nurses were very optimistic about incorporating Harm Reduction counseling into practice, although many agreed that physicians may not have the time to do so and that other clinic staff would need to be involved for successful implementation, as in these statements: I think we’re doing a lot of it. There is more that we can do. I think using this kind of teaching tool would be really good, using a DVD would be good. I think it would have to have a certain class or a setting. Some of the things I could do, some of the tools, you know, a little thing here, a little thing there, because it would take up a lot of time in a regular visit, but I think it could be incorporated very easily. I think it would be really great, really, really great. (Nurse Practitioner) I think it’s not only feasible, I think it should be. We actually do have the luxury of time so much more so than many of our colleagues in many settings. We can bring people back more often medically, when it’s really a mental health issue or a substance use issue. (Nurse Practitioner) These quotes illustrate the ARA290 molecular weight potential for nurse practitioners to act as champions in moving implementation forward; however, patients have lingering concerns to address.The patient as a barrier Clinicians also cited patient-related barriers in their interviews, from getting them to show up for appointments, adhere to medications, or recognize the health problems that their use may cause. In these descriptions of challenges and barriers, clinicians often seemed suspicious of the motives of their own patients. Common challenges are illustrated in these quotes by different clinicians:The biggest thing is people coming back for follow up, that’s the biggest challenge. Even with all of this stuff being put in place, if clients don’t come back to receive the services, it’s extremely hard, and the biggest carrot or the stick, the reason why they come back for primary care is `cause they got to have it in order to get those other services. If they want the.Be good for a group discussion. . . just because I think time wise I think during clinic, it would be very lengthy. They would all want to try it (the demonstration with equipment). (Physician) For any integration to occur at the physician level, a paradigm shift in role may need to occur, as well as additional time for visits. The challenges are really more of a time factor because you’re trying to do it during clinic hours when other patients are waiting to be seen. And it seems like the time flies when you’re in the room with a patient. I don’t know how people see patients in 10 min. (Physician) The time barrier also seemed to be commonly linked to the frustration with other pressing responsibilities, such as paperwork, which interfere with providing more extensive clinical care services. This may be of particular concern in a publicly-funded clinic, whose paperwork requirements and grant writing are often completed by clinical leadership, and require time away from patients to complete. Whether it’s a form to go to the dentist or whatever it is you need, we take care of it, so it isn’t the actual hands on with the patient. A lot of times, it’s the paperwork that takes you a little while to get done. . . Like 30 percent of the time I’m actually taking care of the patient, and 70 percent, I’m taking care of all the paperwork needs that they have. (Physician)Carlberg-Racich (2016), PeerJ, DOI 10.7717/peerj.16/Despite the time barrier, the advanced practice nurses were very optimistic about incorporating Harm Reduction counseling into practice, although many agreed that physicians may not have the time to do so and that other clinic staff would need to be involved for successful implementation, as in these statements: I think we’re doing a lot of it. There is more that we can do. I think using this kind of teaching tool would be really good, using a DVD would be good. I think it would have to have a certain class or a setting. Some of the things I could do, some of the tools, you know, a little thing here, a little thing there, because it would take up a lot of time in a regular visit, but I think it could be incorporated very easily. I think it would be really great, really, really great. (Nurse Practitioner) I think it’s not only feasible, I think it should be. We actually do have the luxury of time so much more so than many of our colleagues in many settings. We can bring people back more often medically, when it’s really a mental health issue or a substance use issue. (Nurse Practitioner) These quotes illustrate the potential for nurse practitioners to act as champions in moving implementation forward; however, patients have lingering concerns to address.The patient as a barrier Clinicians also cited patient-related barriers in their interviews, from getting them to show up for appointments, adhere to medications, or recognize the health problems that their use may cause. In these descriptions of challenges and barriers, clinicians often seemed suspicious of the motives of their own patients. Common challenges are illustrated in these quotes by different clinicians:The biggest thing is people coming back for follow up, that’s the biggest challenge. Even with all of this stuff being put in place, if clients don’t come back to receive the services, it’s extremely hard, and the biggest carrot or the stick, the reason why they come back for primary care is `cause they got to have it in order to get those other services. If they want the.

D communication [13?7] have been extensively studied in the past in order

D communication [13?7] have been extensively studied in the past in order to understand better the way in which they affect the wealth, resilience and function of social systems on global, regional, national and sub-national scales. With our work we aim to address the general question of whether structural network properties of different flow networks purchase AZD-8055 between countries can be used to produce proxy indicators for the socioeconomic profile of a country.Methodology and DataIn this work, we explore over four years of daily postal data records between all countries by comparing them to other global flow networks, such as the trade, migration and digital networks. We show how the network properties of global flow networks can approximate critical socioeconomic indicators and how network communities formed across physical and digital flow networks can reveal socioeconomic similarities. Real-time measurements of international flow networks can ultimately act as global monitors of wellbeing with positive implications for international development efforts. Using knowledge about the way in which countries interact through flows of goods, people and information, we use the principles of multiplexity theory to understand the strength of international ties and the network communities they form. In this section, we will detail the methods used to perform our analysis and the various datasets with focus on the international postal network (IPN), which has previously not been described.Global MultiplexityMultiplexity, or the multiple layers of interactions between the same entities, has been explored in a wide range of systems from global air transportation [18] to massive online multiplayerPLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,2 /The International Postal Network and Other Global Flows as Proxies for National Wellbeinggames [19]. In [20], the author studied the implications of multiple media usage on social ties in an academic organisation and discovered that PD98059MedChemExpress PD98059 multiplex ties (those which use multiple media) indicate a stronger bond. This has been empirically evaluated on networks with both geographical and social interactions recently [21], where it was found that people share a stronger bond when observed to communicate through many different media. These findings support the intuition that a pair of nodes enjoy a stronger relationship if they are better connected across several diverse network layers. The multichannel exchange of information or goods, offers a simple and reliable way of estimating tie strength but has not been applied to international networks of flows until now. Multiplex network model. A natural extension of a network in which edges between pairs of nodes represent a single kind of flow between those nodes, is to a multiplex network [22] including several qualitatively different kinds of flows which may each be understood as a single distinct layer. The advantages of a multiplex model is that the presence of several different network layers has been consistently shown to be more informative than a single layer [23?6]. A comprehensive review of multiplex network models can be found in [27], however, in this work we will apply a simple multiplex model to capture the multiple flow interactions which we will describe in the following section. A multiplex network is one where multiple connections exist between the same entities yet a different set of neighbours exists for a node in each layer [28]. Although many possible repr.D communication [13?7] have been extensively studied in the past in order to understand better the way in which they affect the wealth, resilience and function of social systems on global, regional, national and sub-national scales. With our work we aim to address the general question of whether structural network properties of different flow networks between countries can be used to produce proxy indicators for the socioeconomic profile of a country.Methodology and DataIn this work, we explore over four years of daily postal data records between all countries by comparing them to other global flow networks, such as the trade, migration and digital networks. We show how the network properties of global flow networks can approximate critical socioeconomic indicators and how network communities formed across physical and digital flow networks can reveal socioeconomic similarities. Real-time measurements of international flow networks can ultimately act as global monitors of wellbeing with positive implications for international development efforts. Using knowledge about the way in which countries interact through flows of goods, people and information, we use the principles of multiplexity theory to understand the strength of international ties and the network communities they form. In this section, we will detail the methods used to perform our analysis and the various datasets with focus on the international postal network (IPN), which has previously not been described.Global MultiplexityMultiplexity, or the multiple layers of interactions between the same entities, has been explored in a wide range of systems from global air transportation [18] to massive online multiplayerPLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,2 /The International Postal Network and Other Global Flows as Proxies for National Wellbeinggames [19]. In [20], the author studied the implications of multiple media usage on social ties in an academic organisation and discovered that multiplex ties (those which use multiple media) indicate a stronger bond. This has been empirically evaluated on networks with both geographical and social interactions recently [21], where it was found that people share a stronger bond when observed to communicate through many different media. These findings support the intuition that a pair of nodes enjoy a stronger relationship if they are better connected across several diverse network layers. The multichannel exchange of information or goods, offers a simple and reliable way of estimating tie strength but has not been applied to international networks of flows until now. Multiplex network model. A natural extension of a network in which edges between pairs of nodes represent a single kind of flow between those nodes, is to a multiplex network [22] including several qualitatively different kinds of flows which may each be understood as a single distinct layer. The advantages of a multiplex model is that the presence of several different network layers has been consistently shown to be more informative than a single layer [23?6]. A comprehensive review of multiplex network models can be found in [27], however, in this work we will apply a simple multiplex model to capture the multiple flow interactions which we will describe in the following section. A multiplex network is one where multiple connections exist between the same entities yet a different set of neighbours exists for a node in each layer [28]. Although many possible repr.

Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed

Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed in vivo that 10?20 compressive strain of cartilage led to about 5?3 cell width strain, depending on the area the cells were located [12]. Similarly, it has recently been calculated that the Green-Lagrange strain for cell width increased by 0.17 ?0.02 when bovine cartilage tissue was compressed with a 15 nominal tissue strain [91]. Extreme tissue strains of 80 cartilage compression increased the cell strain only by an additional 2? [95,96]. This suggests that chondrocytes in vivo are not GSK-1605786 site subjected to more than 15 cell elongation. However, one has to consider that chondrocytes come from different layers within articular cartilage. Within these layers cells experience different physical forces and may therefore respond differently to the same strain magnitudes. Nonetheless, as showed in two of the reviewed papers, chondrocytes might also tolerate higher strains (20 ; 24 ) without inducing catabolic actions, although these strains might rather be un-physiologic [14,52]. There is a fine balance between anabolic and catabolic actions in chondrocytes in response to CTS. We suggest that in a non-inflammatory environment loading protocols below 3 strain, 0.17 Hz and 2 h result in weak or no order Vercirnon biological responses. Loading protocols between 3?0 strain, 0.17 Hz–0.5 Hz and 2?2 h tend to induce anabolic responses, whereas above 10 strain, 0.5 Hz and 12 h, catabolic events occur. However, this review not only shows that each of the three loading parameters (magnitude, frequency, duration) but also that the environment of the cell contributes to the shift towards either anabolic or catabolic actions. To provide better comparability of studies and better transition to three-dimensional conditions, we suggest considering the following hints in the future: Loading conditions should be as physiological as possible and should include pauses. Therefore, we advise to apply loading frequencies between 0.5 and 2.5 Hz, loading magnitudes between 0.5 and 15 , and loading durations shorter than 12 h. Further, culture plates should be uncoated or coated with the cartilagespecific collagen II. Data should be collected not only immediately after the last loading cycle but also after a recovery time. All parameters that could affect the cellular outcome should be explained in details.PLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,20 /Cyclic Tensile Strain and Chondrocyte MetabolismConclusionResults from in vitro experiments with CTS disclose further information about the effect of mechanical signals on the biological response of chondrocytes. Many factors are involved in the synthesis and remodeling of the ECM in response to loading. It is important to look not only at single isolated parameters and to combine information from different studies. A better understanding of the relationship between specific loading parameters and chondrocyte response will be useful for the development of tissue engineered cartilage. Furthermore, the simulation of an inflammatory environment allows new insights into the anabolic capabilities of specific loading protocols in rehabilitation and therapy of degenerative joint disease like osteoarthritis.Supporting InformationS1 Checklist. PRISMA checklist. (PDF)Author ContributionsConceived and designed the experiments: JB FZ GB AN. Analyzed the data: JB FZ GB AN. Wrote the paper: JB FZ GB AN. Literature search: JB AN.Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed in vivo that 10?20 compressive strain of cartilage led to about 5?3 cell width strain, depending on the area the cells were located [12]. Similarly, it has recently been calculated that the Green-Lagrange strain for cell width increased by 0.17 ?0.02 when bovine cartilage tissue was compressed with a 15 nominal tissue strain [91]. Extreme tissue strains of 80 cartilage compression increased the cell strain only by an additional 2? [95,96]. This suggests that chondrocytes in vivo are not subjected to more than 15 cell elongation. However, one has to consider that chondrocytes come from different layers within articular cartilage. Within these layers cells experience different physical forces and may therefore respond differently to the same strain magnitudes. Nonetheless, as showed in two of the reviewed papers, chondrocytes might also tolerate higher strains (20 ; 24 ) without inducing catabolic actions, although these strains might rather be un-physiologic [14,52]. There is a fine balance between anabolic and catabolic actions in chondrocytes in response to CTS. We suggest that in a non-inflammatory environment loading protocols below 3 strain, 0.17 Hz and 2 h result in weak or no biological responses. Loading protocols between 3?0 strain, 0.17 Hz–0.5 Hz and 2?2 h tend to induce anabolic responses, whereas above 10 strain, 0.5 Hz and 12 h, catabolic events occur. However, this review not only shows that each of the three loading parameters (magnitude, frequency, duration) but also that the environment of the cell contributes to the shift towards either anabolic or catabolic actions. To provide better comparability of studies and better transition to three-dimensional conditions, we suggest considering the following hints in the future: Loading conditions should be as physiological as possible and should include pauses. Therefore, we advise to apply loading frequencies between 0.5 and 2.5 Hz, loading magnitudes between 0.5 and 15 , and loading durations shorter than 12 h. Further, culture plates should be uncoated or coated with the cartilagespecific collagen II. Data should be collected not only immediately after the last loading cycle but also after a recovery time. All parameters that could affect the cellular outcome should be explained in details.PLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,20 /Cyclic Tensile Strain and Chondrocyte MetabolismConclusionResults from in vitro experiments with CTS disclose further information about the effect of mechanical signals on the biological response of chondrocytes. Many factors are involved in the synthesis and remodeling of the ECM in response to loading. It is important to look not only at single isolated parameters and to combine information from different studies. A better understanding of the relationship between specific loading parameters and chondrocyte response will be useful for the development of tissue engineered cartilage. Furthermore, the simulation of an inflammatory environment allows new insights into the anabolic capabilities of specific loading protocols in rehabilitation and therapy of degenerative joint disease like osteoarthritis.Supporting InformationS1 Checklist. PRISMA checklist. (PDF)Author ContributionsConceived and designed the experiments: JB FZ GB AN. Analyzed the data: JB FZ GB AN. Wrote the paper: JB FZ GB AN. Literature search: JB AN.

Induce the release of calcium from internal stores within neuronal cells

Induce the release of calcium from internal stores within neuronal cells (285). Sublytic concentrations of HlgCB, and, to a lesser extent, HlgAB and PVL, are capable of stimulating glutamate release from cerebellar granular neurons. The release of glutamate was subsequently determined to be a direct consequence of alterations in intracellular calcium release that were induced by leucocidin cellular engagement (285). As a result of this study, it has been suggested that the leucocidins could foreseeably play a role in neuronal tissue damage, thereby influencing the perception of pain during invasive infection with S. aureus. A recent study suggested that S. aureus is indeed able to LIMKI 3MedChemExpress LIMKI 3 directly induce sensations of pain through the action of a pore-forming toxin (in this case, alpha-hemolysin) on nociceptive neurons; however, the bicomponent leucocidins were not implicated (286). Thus, the biological functions of glutamate release caused by HlgCB on granular neurons remain to be determined.MIXED PORES AND TOXIN SYNERGISMThe genes encoding the S and F subunits of a given leucocidin (LukED, LukAB, LukSF-PV, LukMF=, and HlgCB) sit directly adjacent to one NVP-BEZ235 cancer another in the S. aureus chromosome and are cotranscribed (Fig. 4). The pairing of the S subunit with its genetically linked F subunit always results in the formation of an active toxin on target host immune cells. As such, native pairings of leucocid-June 2014 Volume 78 Numbermmbr.asm.orgAlonzo and Torresins are assumed to be the most common biologically active toxins seen in vivo. However, the high degree of sequence similarity among the leucocidins and the unconventional pairing of HlgA with HlgB, despite being translated from independent transcripts, imply that other mixed pairings of leucocidins may be able to form biologically active toxins capable of causing lytic activity or influencing the responses of host cells. Indeed, Prevost et al. performed studies with mixed-subunit pairings of gamma-hemolysin and PVL and found that while hemolytic activity was restricted to pairings of gamma-hemolysin subunits only, PMN lytic activity was not (98). Combinations of LukF-PV and either HlgA or HlgC and combinations of HlgB and LukS-PV caused lysis of primary PMNs (98). In addition, Colin and Monteil provided compelling evidence that mixed pairings of gamma-hemolysin and PVL subunits can induce immune cell activation by priming neutrophils with similar capacities (265). Upon the identification of LukED, additional combinations of leucocidin subunits were found to have lytic activity on both RBCs and PMNs. Hemolytic activity was seen for a number of nonconventional subunit combinations, including LukE plus HlgB, HlgA plus LukD, and HlgA plus LukF-PV (93). An even greater repertoire of toxin combinations exhibited activity on PMNs, as determined by induction of calcium mobilization. However, measurement of ethidium bromide uptake as a readout for pore formation demonstrated that mixed subunits of gamma-hemolysin and PVL were the only toxin combinations capable of inducing robust cell lysis, consistent with what had previously been described (93). In contrast, Morinaga et al. demonstrated that their identified “variant” of LukED (later determined to be highly conserved in nearly all sequenced strains of S. aureus) could form active toxins through nonconventional subunit pairings of both PVL and gamma-hemolysin subunits, indicating that the overall diversity of active toxins can become quite large (9.Induce the release of calcium from internal stores within neuronal cells (285). Sublytic concentrations of HlgCB, and, to a lesser extent, HlgAB and PVL, are capable of stimulating glutamate release from cerebellar granular neurons. The release of glutamate was subsequently determined to be a direct consequence of alterations in intracellular calcium release that were induced by leucocidin cellular engagement (285). As a result of this study, it has been suggested that the leucocidins could foreseeably play a role in neuronal tissue damage, thereby influencing the perception of pain during invasive infection with S. aureus. A recent study suggested that S. aureus is indeed able to directly induce sensations of pain through the action of a pore-forming toxin (in this case, alpha-hemolysin) on nociceptive neurons; however, the bicomponent leucocidins were not implicated (286). Thus, the biological functions of glutamate release caused by HlgCB on granular neurons remain to be determined.MIXED PORES AND TOXIN SYNERGISMThe genes encoding the S and F subunits of a given leucocidin (LukED, LukAB, LukSF-PV, LukMF=, and HlgCB) sit directly adjacent to one another in the S. aureus chromosome and are cotranscribed (Fig. 4). The pairing of the S subunit with its genetically linked F subunit always results in the formation of an active toxin on target host immune cells. As such, native pairings of leucocid-June 2014 Volume 78 Numbermmbr.asm.orgAlonzo and Torresins are assumed to be the most common biologically active toxins seen in vivo. However, the high degree of sequence similarity among the leucocidins and the unconventional pairing of HlgA with HlgB, despite being translated from independent transcripts, imply that other mixed pairings of leucocidins may be able to form biologically active toxins capable of causing lytic activity or influencing the responses of host cells. Indeed, Prevost et al. performed studies with mixed-subunit pairings of gamma-hemolysin and PVL and found that while hemolytic activity was restricted to pairings of gamma-hemolysin subunits only, PMN lytic activity was not (98). Combinations of LukF-PV and either HlgA or HlgC and combinations of HlgB and LukS-PV caused lysis of primary PMNs (98). In addition, Colin and Monteil provided compelling evidence that mixed pairings of gamma-hemolysin and PVL subunits can induce immune cell activation by priming neutrophils with similar capacities (265). Upon the identification of LukED, additional combinations of leucocidin subunits were found to have lytic activity on both RBCs and PMNs. Hemolytic activity was seen for a number of nonconventional subunit combinations, including LukE plus HlgB, HlgA plus LukD, and HlgA plus LukF-PV (93). An even greater repertoire of toxin combinations exhibited activity on PMNs, as determined by induction of calcium mobilization. However, measurement of ethidium bromide uptake as a readout for pore formation demonstrated that mixed subunits of gamma-hemolysin and PVL were the only toxin combinations capable of inducing robust cell lysis, consistent with what had previously been described (93). In contrast, Morinaga et al. demonstrated that their identified “variant” of LukED (later determined to be highly conserved in nearly all sequenced strains of S. aureus) could form active toxins through nonconventional subunit pairings of both PVL and gamma-hemolysin subunits, indicating that the overall diversity of active toxins can become quite large (9.

From each other (Fig. 1a). When making a second MDS analysis

From each other (Fig. 1a). When making a second MDS analysis of the aforementioned seven breeds (Fig. 1b), we were able to distinguish the Gallega sheep from the other populations. These results were consistent with the Admixture analysis (Fig. 2), which showed that Canaria de Pelo, Roja Mallorquina, Latxa and order Stattic Churra breeds have a well defined genetic identity. In contrast, Castellana, Ojalada,Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/Figure 2. Admixture analysis of 11 Spanish ovine breeds: Castellana (CASTEL), Churra (CHURRA), Ojalada (OJALAD), Rasa Aragonesa (RASA AR), Xisqueta (XISQUE), Ripollesa (RIPOLL), Latxa (LATXA), Canaria de Pelo (CANARI), Roja Mallorquina (ROJA MAR), Gallega (GALLEG) and Segure (SEGURE). We set the number of clusters to K = 7 (this K-value had the lowest cross-validation error).Rasa Aragonesa, Xisqueta, Ripollesa, Gallega and Segure sheep share a similar genetic background. These findings are consistent with the weak population structure observed in ovine breeds with a worldwide distribution10. There are reports that indicate that Canaria de Pelo, the only hair sheep breed in Spain, became extinct in the Canary islands during the 16?7th centuries and that current populations descend from Pelibuey sheep brought from Venezuela11. This Pelibuey sheep, in turn, may have a Canarian origin because this Atlantic archipelago was an obliged port-of-call for the ships in route to the New World during the 15th century and onwards11. Hair sheep are the most widespread race in Africa because of their excellent adaptation to the highly humid tropical forest12. Linguistic and genetic evidences connect the aborigin Canarian population with the Imazighen peoples indigenous to North Africa13. In consequence, we attribute the high genetic differentiation of the Canaria de Pelo sheep to the fact that it has an African rather than Iberian origin. Geographic isolation, until the discovery of the Canarian archipelago by the Spanish in the 15th century, combined with the occurrence of population bottlenecks may have also contributed to enhance genetic divergence14,15. Roja Mallorquina, Churra and Latxa sheep also had a defined genetic identity (Figs 1 and 2). Roja Mallorquina sheep display phenotypic features that are distinctive of certain breeds from North Africa and Asia such as a fat triangular tail and a red color. Indeed, fat-tailed sheep are particularly abundant in Lybia, Tunisia and Algeria and it is assumed that they were introduced from the Middle East12. Churra is one of the most important milking sheep breeds in Spain and it is StatticMedChemExpress Stattic mainly raised in Castile and Leon, while Latxa has a lower census and a more restricted geographic distribution in Navarra and the Basque Country. The classical phenotypic classification of ovine Spanish breeds proposed by Antonio S chez-Belda highlights the existence of four main lineages16: (1) Churro (Churra and Latxa breeds, that have a coarse wool), (2) Merino (not represented in our dataset), (3) Medium Fine Wool (Segure , Gallega, Ripollesa, Rasa Aragonesa, Castellana and others), and (4) Iberian (Xisqueta, Ojalada and others). Our genetic data do not support the existence of a substantial genetic divergence between the Medium Fine Wool and the Iberian breeds. As shown in Fig. 1b, Ojalada and Xisqueta sheep are not significantly differentiated from their Segure , Ripollesa, Gallega, Rasa Aragonesa and Castellana counterparts, suggesting that these.From each other (Fig. 1a). When making a second MDS analysis of the aforementioned seven breeds (Fig. 1b), we were able to distinguish the Gallega sheep from the other populations. These results were consistent with the Admixture analysis (Fig. 2), which showed that Canaria de Pelo, Roja Mallorquina, Latxa and Churra breeds have a well defined genetic identity. In contrast, Castellana, Ojalada,Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/Figure 2. Admixture analysis of 11 Spanish ovine breeds: Castellana (CASTEL), Churra (CHURRA), Ojalada (OJALAD), Rasa Aragonesa (RASA AR), Xisqueta (XISQUE), Ripollesa (RIPOLL), Latxa (LATXA), Canaria de Pelo (CANARI), Roja Mallorquina (ROJA MAR), Gallega (GALLEG) and Segure (SEGURE). We set the number of clusters to K = 7 (this K-value had the lowest cross-validation error).Rasa Aragonesa, Xisqueta, Ripollesa, Gallega and Segure sheep share a similar genetic background. These findings are consistent with the weak population structure observed in ovine breeds with a worldwide distribution10. There are reports that indicate that Canaria de Pelo, the only hair sheep breed in Spain, became extinct in the Canary islands during the 16?7th centuries and that current populations descend from Pelibuey sheep brought from Venezuela11. This Pelibuey sheep, in turn, may have a Canarian origin because this Atlantic archipelago was an obliged port-of-call for the ships in route to the New World during the 15th century and onwards11. Hair sheep are the most widespread race in Africa because of their excellent adaptation to the highly humid tropical forest12. Linguistic and genetic evidences connect the aborigin Canarian population with the Imazighen peoples indigenous to North Africa13. In consequence, we attribute the high genetic differentiation of the Canaria de Pelo sheep to the fact that it has an African rather than Iberian origin. Geographic isolation, until the discovery of the Canarian archipelago by the Spanish in the 15th century, combined with the occurrence of population bottlenecks may have also contributed to enhance genetic divergence14,15. Roja Mallorquina, Churra and Latxa sheep also had a defined genetic identity (Figs 1 and 2). Roja Mallorquina sheep display phenotypic features that are distinctive of certain breeds from North Africa and Asia such as a fat triangular tail and a red color. Indeed, fat-tailed sheep are particularly abundant in Lybia, Tunisia and Algeria and it is assumed that they were introduced from the Middle East12. Churra is one of the most important milking sheep breeds in Spain and it is mainly raised in Castile and Leon, while Latxa has a lower census and a more restricted geographic distribution in Navarra and the Basque Country. The classical phenotypic classification of ovine Spanish breeds proposed by Antonio S chez-Belda highlights the existence of four main lineages16: (1) Churro (Churra and Latxa breeds, that have a coarse wool), (2) Merino (not represented in our dataset), (3) Medium Fine Wool (Segure , Gallega, Ripollesa, Rasa Aragonesa, Castellana and others), and (4) Iberian (Xisqueta, Ojalada and others). Our genetic data do not support the existence of a substantial genetic divergence between the Medium Fine Wool and the Iberian breeds. As shown in Fig. 1b, Ojalada and Xisqueta sheep are not significantly differentiated from their Segure , Ripollesa, Gallega, Rasa Aragonesa and Castellana counterparts, suggesting that these.

Acceptances of ordinary favorable roles and total SPQ scores. This was

Acceptances of LY2510924 supplement ordinary favorable roles and total SPQ scores. This was the case (Fisher Z-transform, P = 0.002). This was also observed for the disorganization factor (Fisher Z-transform, P = 0.003), the delusionlike-ideation factor (Fisher Z-transform, P = 0.005) and the interpersonal one (Fisher Z-transform, P = 0.018). The specificity for extraordinary versus ordinary roles was further demonstrated by the presence of significant differences between the two following correlation coefficients: the one for acceptances of extraordinary unfavorable roles and the total SPQ scores, and the one for acceptances of ordinary unfavorable roles and the total SPQ scores (Fisher Z-transform, P = 0.014). No such differences were observed for the total PDI correlation coefficients and for the PDI subscales’ correlation coefficients. Regardless of their favorability, the higher the SPQ score, the greater the number of extraordinary roles that were accepted (see Figures 1b and d). A multiple regression analysis was performed toPublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al3 explore whether percentages of accepted roles for each category combination could complement each other in predicting total SPQ scores and/or whether some conditions would render others insignificant. A significant regression equation was found (F (4, 202) = 11.57, P = 2E – 08), with an R2 of 0.189. The standardized -coefficients were as follows: positive for extraordinary unfavorable ( = 0.280, P = 0.026), for extraordinary favorable ( = 0.238, P = 0.047), and for ordinary unfavorable roles ( = 0.071, P = 0.511), and negative for ordinary favorable roles ( = 0.212, P = 0.041). The same regression analysis was performed to predict disorganization. It was significant (F(4, 202) = 10.14, P = 1.7E – 7), with an R2 of 0.170. The standardized -coefficient were as follows, positive for extraordinary unfavorable ( = 0.259, P = 0.042), for extraordinary favorable ( = 0.226, P = 0.063), and for ordinary unfavorable roles ( = 0.095, P = 0.386), and again negative for ordinary favorable roles ( = – 0.235, P = 0.026). The percentages of social roles accepted in each category combination for each of the two SPQ subject-subgroups are shown in Figure 2. The results of the repeated-measures analysis of variance (ANOVA) revealed that ordinary and favorable roles, independently, were more often accepted than their counterparts (F(1, 201) = 435.78, P{0.000001) and (F(1, 201) = 582.84, P{0.000001), respectively. Also, there was an ordinariness ?SPQ group interaction (F(1, 201) = 5.44, P = 0.021) but no three-way interaction was observed. In general, across all categories, individuals with high SPQ scores accepted more social roles than those with low SPQ scores (F(1, 201) = 18.95, P = 0.000013; see Figure 2). Reaction times Mean reaction times are shown in Figure 3 High accepters of extraordinary roles appeared faster at accepting all roles (M = 1038, s.d. = 258) and slower at rejecting them (M = 1,084, s.d. = 303) than low accepters (M = 1,099, s.d. = 299) and (M = 992, s.d. = 257), respectively. The mixed-model ANOVA revealed that this acceptance ?subgroup interaction was significant (F(1, 163) = 55.56, P = 5E – 12). Post hoc MK-571 (sodium salt) web analyses using independent samples t-tests showed that high accepters were significantly slower at rejecting extraordinary favorable and unfavorable roles than low accepters, (t(177) = – 3.Acceptances of ordinary favorable roles and total SPQ scores. This was the case (Fisher Z-transform, P = 0.002). This was also observed for the disorganization factor (Fisher Z-transform, P = 0.003), the delusionlike-ideation factor (Fisher Z-transform, P = 0.005) and the interpersonal one (Fisher Z-transform, P = 0.018). The specificity for extraordinary versus ordinary roles was further demonstrated by the presence of significant differences between the two following correlation coefficients: the one for acceptances of extraordinary unfavorable roles and the total SPQ scores, and the one for acceptances of ordinary unfavorable roles and the total SPQ scores (Fisher Z-transform, P = 0.014). No such differences were observed for the total PDI correlation coefficients and for the PDI subscales’ correlation coefficients. Regardless of their favorability, the higher the SPQ score, the greater the number of extraordinary roles that were accepted (see Figures 1b and d). A multiple regression analysis was performed toPublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al3 explore whether percentages of accepted roles for each category combination could complement each other in predicting total SPQ scores and/or whether some conditions would render others insignificant. A significant regression equation was found (F (4, 202) = 11.57, P = 2E – 08), with an R2 of 0.189. The standardized -coefficients were as follows: positive for extraordinary unfavorable ( = 0.280, P = 0.026), for extraordinary favorable ( = 0.238, P = 0.047), and for ordinary unfavorable roles ( = 0.071, P = 0.511), and negative for ordinary favorable roles ( = 0.212, P = 0.041). The same regression analysis was performed to predict disorganization. It was significant (F(4, 202) = 10.14, P = 1.7E – 7), with an R2 of 0.170. The standardized -coefficient were as follows, positive for extraordinary unfavorable ( = 0.259, P = 0.042), for extraordinary favorable ( = 0.226, P = 0.063), and for ordinary unfavorable roles ( = 0.095, P = 0.386), and again negative for ordinary favorable roles ( = – 0.235, P = 0.026). The percentages of social roles accepted in each category combination for each of the two SPQ subject-subgroups are shown in Figure 2. The results of the repeated-measures analysis of variance (ANOVA) revealed that ordinary and favorable roles, independently, were more often accepted than their counterparts (F(1, 201) = 435.78, P{0.000001) and (F(1, 201) = 582.84, P{0.000001), respectively. Also, there was an ordinariness ?SPQ group interaction (F(1, 201) = 5.44, P = 0.021) but no three-way interaction was observed. In general, across all categories, individuals with high SPQ scores accepted more social roles than those with low SPQ scores (F(1, 201) = 18.95, P = 0.000013; see Figure 2). Reaction times Mean reaction times are shown in Figure 3 High accepters of extraordinary roles appeared faster at accepting all roles (M = 1038, s.d. = 258) and slower at rejecting them (M = 1,084, s.d. = 303) than low accepters (M = 1,099, s.d. = 299) and (M = 992, s.d. = 257), respectively. The mixed-model ANOVA revealed that this acceptance ?subgroup interaction was significant (F(1, 163) = 55.56, P = 5E – 12). Post hoc analyses using independent samples t-tests showed that high accepters were significantly slower at rejecting extraordinary favorable and unfavorable roles than low accepters, (t(177) = – 3.

Graphic evidence to illuminate exactly how families are reorganizing themselves in

Graphic evidence to illuminate exactly how families are reorganizing themselves in order to maintain kin-based care in this context. I show how a novel way of negotiating for the care of orphans has emerged that no longer privileges patrilocality. While other regional studies have also noted a move away from ideals of patrilineality in fostering patterns (Adato et al. 2005; Howard et al. 2006; Oleke, Blystad Rekdal 2005), this article looks at how deeply embedded patrilineal ideals persist despite practices that seemingly subvert them. Among Basotho families, there has been a gradual shift towards increasing care by maternal relatives, the majority of whom are grandmothers. Paradoxically, the process of negotiation and justification that occurs when families are deciding on the locality of care for orphans highlights the continued adherence to the principles of patrilineal descent, while in practice, care has emerged as the strongest motivation for new patterns of social organization. Kinship continues to be intrinsic to the very notion of care; as a result, few orphans are cared for outside of the family. Increasingly, it is the willingness to care, or what Borneman calls ‘processes of voluntary affiliation’ (1997: 574), as demonstrated by everyday acts of caring, that have become most important in influencing patterns of child circulation. This, in turn, impacts the very nature of relationships between kin (LY317615 dose Klaits 2010). At the family level, there has been considerable flexibility in caregiving patterns. At the structural level, there has been an increase in matrilocal care that remains to be understood as part of a patrilineal system of fostering. The gap that exists between Basotho’s kinship ideology and their caring practices can be explained, in part, by the differentiation Bourdieu makes between ‘official’ and ‘practical’ kin. Lixisenatide web Whereas ‘official kin’ is the representation of kinship for the Pyrvinium pamoate web public sphere by the group as a whole, ‘practical kin’ is ‘directed towards the satisfaction of the practical interests of an individual or group of individuals’ (Bourdieu 1977: 35). People actively forge relationships based on their practical needs, in spite of the tenets of ‘official kin’ doctrine. While Basotho may frame their negotiations as structured by an inflexible set of rules, in reality they are working within a series of competing ideologies, or, as Comaroff puts it, a ‘repertoire of potential manipulations’ (1978: 4). Far from being a simple dichotomy between stated norms and practices, relatedness is processual in nature, allowing caregivers to navigate an array of seemingly conflicting possibilities structured by patrilineal ideals, which are inevitably constrained by the political-economic and social context of which they are a part. Caregivers work within these constraints, often emphasizing idealized rigidity rather than flexibility, in order to make the desired forms ofAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript3Lesotho has a 23.6 per cent HIV-prevalence rate, the second highest Lasalocid (sodium) biological activity globally (UNAIDS 2012). J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagerelatedness appear more or less novel, traditional, or incompatible, depending on their intended outcomes. This article will explore how and why a decline in customary patrilineal practices has not been matched by their lessened importance. As many of the following case studies show, bridewealth payment is particularly p.Graphic evidence to illuminate exactly how families are reorganizing themselves in order to maintain kin-based care in this context. I show how a novel way of negotiating for the care of orphans has emerged that no longer privileges patrilocality. While other regional studies have also noted a move away from ideals of patrilineality in fostering patterns (Adato et al. 2005; Howard et al. 2006; Oleke, Blystad Rekdal 2005), this article looks at how deeply embedded patrilineal ideals persist despite practices that seemingly subvert them. Among Basotho families, there has been a gradual shift towards increasing care by maternal relatives, the majority of whom are grandmothers. Paradoxically, the process of negotiation and justification that occurs when families are deciding on the locality of care for orphans highlights the continued adherence to the principles of patrilineal descent, while in practice, care has emerged as the strongest motivation for new patterns of social organization. Kinship continues to be intrinsic to the very notion of care; as a result, few orphans are cared for outside of the family. Increasingly, it is the willingness to care, or what Borneman calls ‘processes of voluntary affiliation’ (1997: 574), as demonstrated by everyday acts of caring, that have become most important in influencing patterns of child circulation. This, in turn, impacts the very nature of relationships between kin (Klaits 2010). At the family level, there has been considerable flexibility in caregiving patterns. At the structural level, there has been an increase in matrilocal care that remains to be understood as part of a patrilineal system of fostering. The gap that exists between Basotho’s kinship ideology and their caring practices can be explained, in part, by the differentiation Bourdieu makes between ‘official’ and ‘practical’ kin. Whereas ‘official kin’ is the representation of kinship for the public sphere by the group as a whole, ‘practical kin’ is ‘directed towards the satisfaction of the practical interests of an individual or group of individuals’ (Bourdieu 1977: 35). People actively forge relationships based on their practical needs, in spite of the tenets of ‘official kin’ doctrine. While Basotho may frame their negotiations as structured by an inflexible set of rules, in reality they are working within a series of competing ideologies, or, as Comaroff puts it, a ‘repertoire of potential manipulations’ (1978: 4). Far from being a simple dichotomy between stated norms and practices, relatedness is processual in nature, allowing caregivers to navigate an array of seemingly conflicting possibilities structured by patrilineal ideals, which are inevitably constrained by the political-economic and social context of which they are a part. Caregivers work within these constraints, often emphasizing idealized rigidity rather than flexibility, in order to make the desired forms ofAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript3Lesotho has a 23.6 per cent HIV-prevalence rate, the second highest globally (UNAIDS 2012). J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagerelatedness appear more or less novel, traditional, or incompatible, depending on their intended outcomes. This article will explore how and why a decline in customary patrilineal practices has not been matched by their lessened importance. As many of the following case studies show, bridewealth payment is particularly p.Graphic evidence to illuminate exactly how families are reorganizing themselves in order to maintain kin-based care in this context. I show how a novel way of negotiating for the care of orphans has emerged that no longer privileges patrilocality. While other regional studies have also noted a move away from ideals of patrilineality in fostering patterns (Adato et al. 2005; Howard et al. 2006; Oleke, Blystad Rekdal 2005), this article looks at how deeply embedded patrilineal ideals persist despite practices that seemingly subvert them. Among Basotho families, there has been a gradual shift towards increasing care by maternal relatives, the majority of whom are grandmothers. Paradoxically, the process of negotiation and justification that occurs when families are deciding on the locality of care for orphans highlights the continued adherence to the principles of patrilineal descent, while in practice, care has emerged as the strongest motivation for new patterns of social organization. Kinship continues to be intrinsic to the very notion of care; as a result, few orphans are cared for outside of the family. Increasingly, it is the willingness to care, or what Borneman calls ‘processes of voluntary affiliation’ (1997: 574), as demonstrated by everyday acts of caring, that have become most important in influencing patterns of child circulation. This, in turn, impacts the very nature of relationships between kin (Klaits 2010). At the family level, there has been considerable flexibility in caregiving patterns. At the structural level, there has been an increase in matrilocal care that remains to be understood as part of a patrilineal system of fostering. The gap that exists between Basotho’s kinship ideology and their caring practices can be explained, in part, by the differentiation Bourdieu makes between ‘official’ and ‘practical’ kin. Whereas ‘official kin’ is the representation of kinship for the public sphere by the group as a whole, ‘practical kin’ is ‘directed towards the satisfaction of the practical interests of an individual or group of individuals’ (Bourdieu 1977: 35). People actively forge relationships based on their practical needs, in spite of the tenets of ‘official kin’ doctrine. While Basotho may frame their negotiations as structured by an inflexible set of rules, in reality they are working within a series of competing ideologies, or, as Comaroff puts it, a ‘repertoire of potential manipulations’ (1978: 4). Far from being a simple dichotomy between stated norms and practices, relatedness is processual in nature, allowing caregivers to navigate an array of seemingly conflicting possibilities structured by patrilineal ideals, which are inevitably constrained by the political-economic and social context of which they are a part. Caregivers work within these constraints, often emphasizing idealized rigidity rather than flexibility, in order to make the desired forms ofAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript3Lesotho has a 23.6 per cent HIV-prevalence rate, the second highest globally (UNAIDS 2012). J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagerelatedness appear more or less novel, traditional, or incompatible, depending on their intended outcomes. This article will explore how and why a decline in customary patrilineal practices has not been matched by their lessened importance. As many of the following case studies show, bridewealth payment is particularly p.Graphic evidence to illuminate exactly how families are reorganizing themselves in order to maintain kin-based care in this context. I show how a novel way of negotiating for the care of orphans has emerged that no longer privileges patrilocality. While other regional studies have also noted a move away from ideals of patrilineality in fostering patterns (Adato et al. 2005; Howard et al. 2006; Oleke, Blystad Rekdal 2005), this article looks at how deeply embedded patrilineal ideals persist despite practices that seemingly subvert them. Among Basotho families, there has been a gradual shift towards increasing care by maternal relatives, the majority of whom are grandmothers. Paradoxically, the process of negotiation and justification that occurs when families are deciding on the locality of care for orphans highlights the continued adherence to the principles of patrilineal descent, while in practice, care has emerged as the strongest motivation for new patterns of social organization. Kinship continues to be intrinsic to the very notion of care; as a result, few orphans are cared for outside of the family. Increasingly, it is the willingness to care, or what Borneman calls ‘processes of voluntary affiliation’ (1997: 574), as demonstrated by everyday acts of caring, that have become most important in influencing patterns of child circulation. This, in turn, impacts the very nature of relationships between kin (Klaits 2010). At the family level, there has been considerable flexibility in caregiving patterns. At the structural level, there has been an increase in matrilocal care that remains to be understood as part of a patrilineal system of fostering. The gap that exists between Basotho’s kinship ideology and their caring practices can be explained, in part, by the differentiation Bourdieu makes between ‘official’ and ‘practical’ kin. Whereas ‘official kin’ is the representation of kinship for the public sphere by the group as a whole, ‘practical kin’ is ‘directed towards the satisfaction of the practical interests of an individual or group of individuals’ (Bourdieu 1977: 35). People actively forge relationships based on their practical needs, in spite of the tenets of ‘official kin’ doctrine. While Basotho may frame their negotiations as structured by an inflexible set of rules, in reality they are working within a series of competing ideologies, or, as Comaroff puts it, a ‘repertoire of potential manipulations’ (1978: 4). Far from being a simple dichotomy between stated norms and practices, relatedness is processual in nature, allowing caregivers to navigate an array of seemingly conflicting possibilities structured by patrilineal ideals, which are inevitably constrained by the political-economic and social context of which they are a part. Caregivers work within these constraints, often emphasizing idealized rigidity rather than flexibility, in order to make the desired forms ofAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript3Lesotho has a 23.6 per cent HIV-prevalence rate, the second highest globally (UNAIDS 2012). J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagerelatedness appear more or less novel, traditional, or incompatible, depending on their intended outcomes. This article will explore how and why a decline in customary patrilineal practices has not been matched by their lessened importance. As many of the following case studies show, bridewealth payment is particularly p.

Graphic evidence to illuminate exactly how families are reorganizing themselves in

Graphic evidence to illuminate exactly how families are reorganizing themselves in order to maintain kin-based care in this context. I show how a novel way of negotiating for the care of orphans has emerged that no longer privileges patrilocality. While other regional studies have also noted a move away from ideals of patrilineality in fostering patterns (Adato et al. 2005; Howard et al. 2006; Oleke, Blystad Rekdal 2005), this article looks at how deeply embedded patrilineal ideals persist despite practices that seemingly subvert them. Among Basotho families, there has been a gradual shift towards increasing care by maternal relatives, the majority of whom are grandmothers. Paradoxically, the process of negotiation and justification that occurs when families are deciding on the locality of care for orphans highlights the continued adherence to the principles of patrilineal descent, while in practice, care has emerged as the strongest motivation for new patterns of social organization. Kinship continues to be intrinsic to the very notion of care; as a result, few orphans are cared for outside of the family. Increasingly, it is the willingness to care, or what Borneman calls ‘processes of voluntary affiliation’ (1997: 574), as demonstrated by everyday acts of caring, that have become most important in influencing patterns of child circulation. This, in turn, impacts the very nature of relationships between kin (Klaits 2010). At the family level, there has been considerable flexibility in caregiving patterns. At the structural level, there has been an increase in matrilocal care that remains to be understood as part of a patrilineal system of fostering. The gap that exists between Basotho’s kinship ideology and their caring practices can be explained, in part, by the differentiation Bourdieu makes between ‘official’ and ‘practical’ kin. Lixisenatide web Whereas ‘official kin’ is the representation of kinship for the Pyrvinium pamoate web public sphere by the group as a whole, ‘practical kin’ is ‘directed towards the satisfaction of the practical interests of an individual or group of individuals’ (Bourdieu 1977: 35). People actively forge relationships based on their practical needs, in spite of the tenets of ‘official kin’ doctrine. While Basotho may frame their negotiations as structured by an inflexible set of rules, in reality they are working within a series of competing ideologies, or, as Comaroff puts it, a ‘repertoire of potential manipulations’ (1978: 4). Far from being a simple dichotomy between stated norms and practices, relatedness is processual in nature, allowing caregivers to navigate an array of seemingly conflicting possibilities structured by patrilineal ideals, which are inevitably constrained by the political-economic and social context of which they are a part. Caregivers work within these constraints, often emphasizing idealized rigidity rather than flexibility, in order to make the desired forms ofAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript3Lesotho has a 23.6 per cent HIV-prevalence rate, the second highest globally (UNAIDS 2012). J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagerelatedness appear more or less novel, traditional, or incompatible, depending on their intended outcomes. This article will explore how and why a decline in customary patrilineal practices has not been matched by their lessened importance. As many of the following case studies show, bridewealth payment is particularly p.Graphic evidence to illuminate exactly how families are reorganizing themselves in order to maintain kin-based care in this context. I show how a novel way of negotiating for the care of orphans has emerged that no longer privileges patrilocality. While other regional studies have also noted a move away from ideals of patrilineality in fostering patterns (Adato et al. 2005; Howard et al. 2006; Oleke, Blystad Rekdal 2005), this article looks at how deeply embedded patrilineal ideals persist despite practices that seemingly subvert them. Among Basotho families, there has been a gradual shift towards increasing care by maternal relatives, the majority of whom are grandmothers. Paradoxically, the process of negotiation and justification that occurs when families are deciding on the locality of care for orphans highlights the continued adherence to the principles of patrilineal descent, while in practice, care has emerged as the strongest motivation for new patterns of social organization. Kinship continues to be intrinsic to the very notion of care; as a result, few orphans are cared for outside of the family. Increasingly, it is the willingness to care, or what Borneman calls ‘processes of voluntary affiliation’ (1997: 574), as demonstrated by everyday acts of caring, that have become most important in influencing patterns of child circulation. This, in turn, impacts the very nature of relationships between kin (Klaits 2010). At the family level, there has been considerable flexibility in caregiving patterns. At the structural level, there has been an increase in matrilocal care that remains to be understood as part of a patrilineal system of fostering. The gap that exists between Basotho’s kinship ideology and their caring practices can be explained, in part, by the differentiation Bourdieu makes between ‘official’ and ‘practical’ kin. Whereas ‘official kin’ is the representation of kinship for the public sphere by the group as a whole, ‘practical kin’ is ‘directed towards the satisfaction of the practical interests of an individual or group of individuals’ (Bourdieu 1977: 35). People actively forge relationships based on their practical needs, in spite of the tenets of ‘official kin’ doctrine. While Basotho may frame their negotiations as structured by an inflexible set of rules, in reality they are working within a series of competing ideologies, or, as Comaroff puts it, a ‘repertoire of potential manipulations’ (1978: 4). Far from being a simple dichotomy between stated norms and practices, relatedness is processual in nature, allowing caregivers to navigate an array of seemingly conflicting possibilities structured by patrilineal ideals, which are inevitably constrained by the political-economic and social context of which they are a part. Caregivers work within these constraints, often emphasizing idealized rigidity rather than flexibility, in order to make the desired forms ofAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript3Lesotho has a 23.6 per cent HIV-prevalence rate, the second highest globally (UNAIDS 2012). J R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPagerelatedness appear more or less novel, traditional, or incompatible, depending on their intended outcomes. This article will explore how and why a decline in customary patrilineal practices has not been matched by their lessened importance. As many of the following case studies show, bridewealth payment is particularly p.

Author ManuscriptBentov and ReedPageof age-related deficits in angiogenesis, which has an

Author ManuscriptBentov and ReedPageof age-related deficits in angiogenesis, which has an adverse effect on the development of an effective microcirculation38. In an explant model, age-related deficiencies in angiogenesis were reversed, in part, by stimulation with angiogenic growth factors39. IIC. Extracellular matrix and tissue remodeling During the last phase of wound healing, the extracellular matrix begins to remodel and the wound undergoes further contraction. Fibroblasts assume a myofibroblast phenotype characterized by bundles of alpha smooth muscle actin-containing microfilaments. Synchronized collagen reorganization occurs by synthesis and catabolism (although at a much slower rate than in previous stages), which allows the granulation tissue to turn into a scar. Deposition and remodeling of collagen is slower in aged animals resulting in less scar formation40. Moreover, the collagen deposited has a looser, more Leupeptin (hemisulfate) structure disorganized matrix that has decreased tensile strength. The changes in aged collagen matrix reflect decreases in circulating factors, in particular reduced levels of TGF-1 – a potent stimulator of collagen synthesis 41. Of note, dermal fibroblasts from aged and young donors exposed to TGF-1 exhibit similar biosynthetic and contractile properties42. Other matrix components43 that are altered with age (Figure 3C) include: decreased osteonectin (also known as secreted protein acidic and rich in cysteine – SPARC), increases in thrombospondin44 and alterations in fibronectin and laminin45, 46. Non-protein components of the extracellular matrix include glycosaminoglycans, such as hyaluronan, which interact with other matrix components to maintain hydration in the dermis. Hyaluronan is a linear disaccharide polymer that can range from 2?5,000 disaccharides with molecular masses up to 2?04 kDa. Hyaluronan size determines its biologic properties: high molecular weight forms can inhibit proliferation and migration of many cell types, whereas middle and lower molecular weight forms usually promote tissue formation46. Hyaluronan content is maintained in aged wound dermis, but its degradation is reduced47. Wound healing also requires matrix get Velpatasvir metalloproteinases (MMPs), which promote cell proliferation and vessel ingrowth by degrading the existing extracellular matrix. MMP activity is balanced, in part, by endogenous tissue inhibitors of metalloproteinases. Aged tissues are associated with dysregulation of MMP activity48, with a tendency toward overexpression of MMPs49 and reduced levels of tissue inhibitors of metalloproteinases50. As highlighted above, alterations occur during each stage of wound repair in aging, and many of these changes negatively impact the microcirculation. Nonetheless, given sufficient time aged animals eventually (age related delay is roughly 30?0 ) catch up to their young counterparts with respect to most aspects of tissue repair51.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIII. The Surgical Context of Wound Repair and AgingMeasures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection52. General pre-operative measures such as smoking cessation and optimal management of co-morbid medical conditions have been reviewed in other contexts53, 54. For the purpose of this review, we will focus on interventions in the peri-operative setting. IIIA. Oxygen administration Wound healing is dependent upon adequate levels.Author ManuscriptBentov and ReedPageof age-related deficits in angiogenesis, which has an adverse effect on the development of an effective microcirculation38. In an explant model, age-related deficiencies in angiogenesis were reversed, in part, by stimulation with angiogenic growth factors39. IIC. Extracellular matrix and tissue remodeling During the last phase of wound healing, the extracellular matrix begins to remodel and the wound undergoes further contraction. Fibroblasts assume a myofibroblast phenotype characterized by bundles of alpha smooth muscle actin-containing microfilaments. Synchronized collagen reorganization occurs by synthesis and catabolism (although at a much slower rate than in previous stages), which allows the granulation tissue to turn into a scar. Deposition and remodeling of collagen is slower in aged animals resulting in less scar formation40. Moreover, the collagen deposited has a looser, more disorganized matrix that has decreased tensile strength. The changes in aged collagen matrix reflect decreases in circulating factors, in particular reduced levels of TGF-1 – a potent stimulator of collagen synthesis 41. Of note, dermal fibroblasts from aged and young donors exposed to TGF-1 exhibit similar biosynthetic and contractile properties42. Other matrix components43 that are altered with age (Figure 3C) include: decreased osteonectin (also known as secreted protein acidic and rich in cysteine – SPARC), increases in thrombospondin44 and alterations in fibronectin and laminin45, 46. Non-protein components of the extracellular matrix include glycosaminoglycans, such as hyaluronan, which interact with other matrix components to maintain hydration in the dermis. Hyaluronan is a linear disaccharide polymer that can range from 2?5,000 disaccharides with molecular masses up to 2?04 kDa. Hyaluronan size determines its biologic properties: high molecular weight forms can inhibit proliferation and migration of many cell types, whereas middle and lower molecular weight forms usually promote tissue formation46. Hyaluronan content is maintained in aged wound dermis, but its degradation is reduced47. Wound healing also requires matrix metalloproteinases (MMPs), which promote cell proliferation and vessel ingrowth by degrading the existing extracellular matrix. MMP activity is balanced, in part, by endogenous tissue inhibitors of metalloproteinases. Aged tissues are associated with dysregulation of MMP activity48, with a tendency toward overexpression of MMPs49 and reduced levels of tissue inhibitors of metalloproteinases50. As highlighted above, alterations occur during each stage of wound repair in aging, and many of these changes negatively impact the microcirculation. Nonetheless, given sufficient time aged animals eventually (age related delay is roughly 30?0 ) catch up to their young counterparts with respect to most aspects of tissue repair51.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIII. The Surgical Context of Wound Repair and AgingMeasures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection52. General pre-operative measures such as smoking cessation and optimal management of co-morbid medical conditions have been reviewed in other contexts53, 54. For the purpose of this review, we will focus on interventions in the peri-operative setting. IIIA. Oxygen administration Wound healing is dependent upon adequate levels.

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the Z-DEVD-FMK dose values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the get Flavopiridol commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in SIS3 chemical information hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and Necrosulfonamide chemical information horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.

T between 6 and 20 weeks, in both cortex and medulla (Table 4 and

T between 6 and 20 weeks, in both cortex and medulla (Table 4 and Fig. 6, panels 1 vs. 4 and 7 vs. 5). 3.5 Correlation analysis The results obtained with Pearson and Spearman analyses were comparable. Spearman correlations with correlation coefficients |0.5| and p values 0.05 are presented in Supplementary Table 1. Degree of PAS staining in glomeruli (PTA) showed a positive correlation with GTA (Table S1, N 1). A positive correlation was observed between numbers of immune-positive tubules and degree of staining in cortex and medulla for eNOS (Table S1, N 2 and 3), nNOS (Table S1, N 4 and 5) and iNOS (Table S1, N 6). Also a positive correlation was seen between numbers of tubules immune-positive for iNOS and nNOS in cortex (Table S1, N 7). Mesangial matrix PAS staining and glomerular tuft expansion showed a number of Pan-RAS-IN-1 chemical information negative correlations with the immunostaining for NOS isoforms. For eNOS in medulla, a negativeActa Histochem. Author manuscript; available in PMC 2017 March 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptMG-132MedChemExpress MG-132 Slyvka et al.Pagecorrelation was observed with GTA (Table S1, N 8). A negative correlation was observed between nNOS in medulla and both PTA (Table S1, N 12) and PTA/GTA (Table S1, N 16 and 17) and for nNOS in cortex with GTA (Table S1, N 9), PTA (Table S1, N 11 and 13), and PTA/GTA (Table S1, N 15). A similar negative correlation was observed between iNOS in cortex and both GTA and PTA (Table S1, N 10 and 14). Please see Table S1 in the section on supplementary data given at the end of this article for details.Author Manuscript Author Manuscript4.2 eNOS4. Discussion4.1 Glomerular staining and morphology Mesangial matrix expansion, glomerular basement membrane thickening and glomerular hypertrophy are key histological findings in early DN (Abrass, 1995, Couser and Johnson, 1994, Kasiske et al., 1985, Schena and Gesualdo, 2005), followed later by glomerular contraction. In the present study, increases in both GTA and PTA were observed in both male and female obese diabetic Zucker rats with age and both GTA and PTA were less in rats on the AO diet indicating a correspondence between diet and matrix proliferation. As mesangial cells are important in regulation of glomerular filtration, this may be related to the improved GFR in 20 week females on the AO diet observed by Slyvka et al. (Slyvka, Inman, 2009). Treatment of STZ-induced diabetic rats (Wistar) with an NO donor has been shown to alleviate extracellular matrix proliferation (ECM) (Hsu et al., 2015), consistent with our finding that the AO-fortified diet also decreases the ECM in diabetic rats.Pathologic changes in the kidney are accompanied by changes in the expression and localization of constitutive and inducible NOS isoforms. In animal models of DN, endothelial damage caused by increased inflammation and excess production of ROS coupled with ineffective NO action leads to compensatory increases in constitutive eNOS and nNOS as well as iNOS (Prabhakar et al., 2007, Tan et al., 2007), eventually compounding and accelerating the damage. In the current experiment, levels of eNOS protein increased with duration of hyperglycemia in glomerular and vascular endothelium, in agreement with the findings of others (Veelken et al., 2000). It is known that eNOS levels are increased in glomerular endothelial cells of patients with DN (Hohenstein, Hugo, 2008). An increase in glomerular eNOS has also been seen in diabetic patients with microalbuminuria (.T between 6 and 20 weeks, in both cortex and medulla (Table 4 and Fig. 6, panels 1 vs. 4 and 7 vs. 5). 3.5 Correlation analysis The results obtained with Pearson and Spearman analyses were comparable. Spearman correlations with correlation coefficients |0.5| and p values 0.05 are presented in Supplementary Table 1. Degree of PAS staining in glomeruli (PTA) showed a positive correlation with GTA (Table S1, N 1). A positive correlation was observed between numbers of immune-positive tubules and degree of staining in cortex and medulla for eNOS (Table S1, N 2 and 3), nNOS (Table S1, N 4 and 5) and iNOS (Table S1, N 6). Also a positive correlation was seen between numbers of tubules immune-positive for iNOS and nNOS in cortex (Table S1, N 7). Mesangial matrix PAS staining and glomerular tuft expansion showed a number of negative correlations with the immunostaining for NOS isoforms. For eNOS in medulla, a negativeActa Histochem. Author manuscript; available in PMC 2017 March 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSlyvka et al.Pagecorrelation was observed with GTA (Table S1, N 8). A negative correlation was observed between nNOS in medulla and both PTA (Table S1, N 12) and PTA/GTA (Table S1, N 16 and 17) and for nNOS in cortex with GTA (Table S1, N 9), PTA (Table S1, N 11 and 13), and PTA/GTA (Table S1, N 15). A similar negative correlation was observed between iNOS in cortex and both GTA and PTA (Table S1, N 10 and 14). Please see Table S1 in the section on supplementary data given at the end of this article for details.Author Manuscript Author Manuscript4.2 eNOS4. Discussion4.1 Glomerular staining and morphology Mesangial matrix expansion, glomerular basement membrane thickening and glomerular hypertrophy are key histological findings in early DN (Abrass, 1995, Couser and Johnson, 1994, Kasiske et al., 1985, Schena and Gesualdo, 2005), followed later by glomerular contraction. In the present study, increases in both GTA and PTA were observed in both male and female obese diabetic Zucker rats with age and both GTA and PTA were less in rats on the AO diet indicating a correspondence between diet and matrix proliferation. As mesangial cells are important in regulation of glomerular filtration, this may be related to the improved GFR in 20 week females on the AO diet observed by Slyvka et al. (Slyvka, Inman, 2009). Treatment of STZ-induced diabetic rats (Wistar) with an NO donor has been shown to alleviate extracellular matrix proliferation (ECM) (Hsu et al., 2015), consistent with our finding that the AO-fortified diet also decreases the ECM in diabetic rats.Pathologic changes in the kidney are accompanied by changes in the expression and localization of constitutive and inducible NOS isoforms. In animal models of DN, endothelial damage caused by increased inflammation and excess production of ROS coupled with ineffective NO action leads to compensatory increases in constitutive eNOS and nNOS as well as iNOS (Prabhakar et al., 2007, Tan et al., 2007), eventually compounding and accelerating the damage. In the current experiment, levels of eNOS protein increased with duration of hyperglycemia in glomerular and vascular endothelium, in agreement with the findings of others (Veelken et al., 2000). It is known that eNOS levels are increased in glomerular endothelial cells of patients with DN (Hohenstein, Hugo, 2008). An increase in glomerular eNOS has also been seen in diabetic patients with microalbuminuria (.

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the buy CPI-455 values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted Thonzonium (bromide) cost phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.

Geting the FGL2 cRIIB Pathway. There are three main approaches currently

Geting the FGL2 cRIIB Pathway. There are three main approaches currently being pursued to modulate the FGL2 cRIIB pathway for clinical benefit: (1) development of rFGL2 (monomeric and oligomeric) to inhibit immune responses; (2) expansion of TIGIT+ Treg expressing high levels of FGL2, which would represent a cellular therapy for transplantation and autoimmune disease; and (3) development of anti-FGL2 monoclonal antibodies to inhibit FGL2 signaling and enhance immune responses in cancer and chronic infections. DC, dendritic cell; PVR, poliovirus receptor; rFGL2, recombinant FGL2; TIGIT, T cell immunoreceptor with Ig and ITIM domains; Treg, regulatory T cell.Rambam Maimonides Medical JournalJuly 2015 Volume 6 Issue 3 eTreg and FGL2 in Alloimmunity and Autoimmunity chronic viral disease as well as parasitic infections. This therapy may hold the potential for using the host immune response against parasites and viruses as opposed to current antiviral and anti-helminthic drugs. Furthermore, patients with impaired immune systems may benefit from anti-FGL2 antibody therapy as an adjuvant to improve immune responses to vaccines. Potential therapies based on modulating the FGL2 cRIIB pathway are highlighted in Figure 5. In conclusion, the FGL2 cRIIB pathway is a critical immunoregulatory pathway that is involved in alloimmunity, autoimmunity, chronic infections, and cancer. Therapies based on either augmenting or inhibiting this pathway hold great promise in treating these diverse medical conditions.
Suzannah BiernoffMEDICAL ARCHIVES AND DIGITAL CULTUREWhen BioShock was released in 2007, reviewers praised the moral complexities of the narrative and the game’s dystopian vision of what Ayn Rand dubbed the “virtue of selfishness”. What critics overlooked was the extent to which the disturbingly realistic artwork and musical score relied on found images and sound, ALS-8176 cost including a recording of distressed breathing from a physician’s website, and digitised First World War medical photographs of soldiers with facial injuries. This article examines the implications of these acts of appropriation from a range of critical perspectives including Susan Sontag’s commentary on the representation of suffering; recent literature on the ethics of computer games; and an online discussion forum in which players of BioShock discuss the moral “grey areas” of the game. In 1997 the Hayward Gallery in London put on a touring exhibition called The Quick and the Dead: Artists and Anatomy. In the book accompanying the exhibition Ludmilla LOXO-101MedChemExpress LOXO-101 Jordanova reflected on the points of contact and dissonance between these two pursuits, art and anatomy: a history encapsulated in the title of her essay, “Happy Marriages and Dangerous Liaisons”. The study and representation of the human body has, since the Renaissance, been constrained by practical and moral considerations — a limited supply of cadavers, the politics of patronage, codes of decorum governing the circumstances in which a naked or dead body could be seen or depicted — but it is only in the last forty or so years that artists have openly exploited the subversive potential of medical themes and images. “Indeed”, writes Jordanova, “in recent decades, medicine has supplied the materials with which artists can openly explore the troubling, unsettling aspects of bodily phenomena” (101). This article concerns one such troubling liaison between medicine and art, although it is true that computer games are not often described as ar.Geting the FGL2 cRIIB Pathway. There are three main approaches currently being pursued to modulate the FGL2 cRIIB pathway for clinical benefit: (1) development of rFGL2 (monomeric and oligomeric) to inhibit immune responses; (2) expansion of TIGIT+ Treg expressing high levels of FGL2, which would represent a cellular therapy for transplantation and autoimmune disease; and (3) development of anti-FGL2 monoclonal antibodies to inhibit FGL2 signaling and enhance immune responses in cancer and chronic infections. DC, dendritic cell; PVR, poliovirus receptor; rFGL2, recombinant FGL2; TIGIT, T cell immunoreceptor with Ig and ITIM domains; Treg, regulatory T cell.Rambam Maimonides Medical JournalJuly 2015 Volume 6 Issue 3 eTreg and FGL2 in Alloimmunity and Autoimmunity chronic viral disease as well as parasitic infections. This therapy may hold the potential for using the host immune response against parasites and viruses as opposed to current antiviral and anti-helminthic drugs. Furthermore, patients with impaired immune systems may benefit from anti-FGL2 antibody therapy as an adjuvant to improve immune responses to vaccines. Potential therapies based on modulating the FGL2 cRIIB pathway are highlighted in Figure 5. In conclusion, the FGL2 cRIIB pathway is a critical immunoregulatory pathway that is involved in alloimmunity, autoimmunity, chronic infections, and cancer. Therapies based on either augmenting or inhibiting this pathway hold great promise in treating these diverse medical conditions.
Suzannah BiernoffMEDICAL ARCHIVES AND DIGITAL CULTUREWhen BioShock was released in 2007, reviewers praised the moral complexities of the narrative and the game’s dystopian vision of what Ayn Rand dubbed the “virtue of selfishness”. What critics overlooked was the extent to which the disturbingly realistic artwork and musical score relied on found images and sound, including a recording of distressed breathing from a physician’s website, and digitised First World War medical photographs of soldiers with facial injuries. This article examines the implications of these acts of appropriation from a range of critical perspectives including Susan Sontag’s commentary on the representation of suffering; recent literature on the ethics of computer games; and an online discussion forum in which players of BioShock discuss the moral “grey areas” of the game. In 1997 the Hayward Gallery in London put on a touring exhibition called The Quick and the Dead: Artists and Anatomy. In the book accompanying the exhibition Ludmilla Jordanova reflected on the points of contact and dissonance between these two pursuits, art and anatomy: a history encapsulated in the title of her essay, “Happy Marriages and Dangerous Liaisons”. The study and representation of the human body has, since the Renaissance, been constrained by practical and moral considerations — a limited supply of cadavers, the politics of patronage, codes of decorum governing the circumstances in which a naked or dead body could be seen or depicted — but it is only in the last forty or so years that artists have openly exploited the subversive potential of medical themes and images. “Indeed”, writes Jordanova, “in recent decades, medicine has supplied the materials with which artists can openly explore the troubling, unsettling aspects of bodily phenomena” (101). This article concerns one such troubling liaison between medicine and art, although it is true that computer games are not often described as ar.

Ent was developed using various sources [39-43]. Mobile augmented reality education

Ent was developed using various sources [39-43]. Mobile augmented reality education (MARE). Augmented reality (AR).b cThe Functional Level Design OverviewMARE provides a prompt, portable tool for medical student learning within the clinical setting in order to transform knowledge into practice. The flexible personal paradigm, which is “more inclusive, discriminating, open, reflective, and emotionally able to change,” is more appropriate for guiding action [43]. The most important function of AR is mixing aspects of the real environment with virtual objects to create Mikamycin B custom synthesis different learning environments. As backed by the learning theories previously discussed, these mixed environments willhttp://mededu.jmir.org/2015/2/e10/be useful for the medical student to form a flexible personal paradigm. We propose the following function structure shown in Figure 3 for developing MARE. The personal paradigm is the starting point of design learning and must transform to become flexible. A physician’s personal paradigm includes his or her personal style of diagnosis, treatment, prescription, and drugs (P-diagnosis, P-treatment, P-prescription and P-drugs, which are four related processes) [13]. The physician’s personal paradigm could be analyzed through observation and deep interviews.XSL?FORenderXJMIR Medical Education 2015 | vol. 1 | iss. 2 | e10 | p.8 (page number not for citation purposes)JMIR MEDICAL EDUCATION Second, by comparing the learners’ personal paradigms with professional expectations, we can describe the learning objectives and check their PP58 site problematic reference. The learning activities cycle, which focuses on improving one’s personal paradigm from feeling, watching, and thinking to doing, will help learners reflect on their practice and change the problematic frames of reference. After identifying the learning objectives, an AR environment of MARE framework should be designed. Four oriented learning environments, which can add different virtual objects to the real clinical environment, create multiple sensory channels for learning [45]. Affective-oriented environments affect health care learners’ feelings. Perception-oriented environments are beneficial for observation. Symbol-oriented environments are particularly useful for thinking, and behavior-oriented environments are beneficial for doing [42]. The real clinical environments are the immediate context in which a connection is needed between learning and practice. The real clinical environment is the anchor and scaffold upon which learners are encouraged to learn. The real clinical environment includes physical environments and social environments. The content in physical environments, such as patients and their disease, microbiological samples, documentation and clinical notes, medical equipment, drugs,Figure 3. MARE function structure.Zhu et al and consequences of bacterial resistance, can be the anchor to trigger a learning activity, which then aims to fulfill a learning outcome within the appropriate therapeutic stage. The social environment (ie, local culture and customs, organizational norms, and policy) shapes the content and forms of learning, which should be more instrumental or communicative. Virtual environments, which are simulated with computers, extend the real-world environment with an assurance of safety and enable or increase opportunities for engagement. Although it may be necessary or attractive for medical learners to learn in the clinical context, observing a real-wo.Ent was developed using various sources [39-43]. Mobile augmented reality education (MARE). Augmented reality (AR).b cThe Functional Level Design OverviewMARE provides a prompt, portable tool for medical student learning within the clinical setting in order to transform knowledge into practice. The flexible personal paradigm, which is “more inclusive, discriminating, open, reflective, and emotionally able to change,” is more appropriate for guiding action [43]. The most important function of AR is mixing aspects of the real environment with virtual objects to create different learning environments. As backed by the learning theories previously discussed, these mixed environments willhttp://mededu.jmir.org/2015/2/e10/be useful for the medical student to form a flexible personal paradigm. We propose the following function structure shown in Figure 3 for developing MARE. The personal paradigm is the starting point of design learning and must transform to become flexible. A physician’s personal paradigm includes his or her personal style of diagnosis, treatment, prescription, and drugs (P-diagnosis, P-treatment, P-prescription and P-drugs, which are four related processes) [13]. The physician’s personal paradigm could be analyzed through observation and deep interviews.XSL?FORenderXJMIR Medical Education 2015 | vol. 1 | iss. 2 | e10 | p.8 (page number not for citation purposes)JMIR MEDICAL EDUCATION Second, by comparing the learners’ personal paradigms with professional expectations, we can describe the learning objectives and check their problematic reference. The learning activities cycle, which focuses on improving one’s personal paradigm from feeling, watching, and thinking to doing, will help learners reflect on their practice and change the problematic frames of reference. After identifying the learning objectives, an AR environment of MARE framework should be designed. Four oriented learning environments, which can add different virtual objects to the real clinical environment, create multiple sensory channels for learning [45]. Affective-oriented environments affect health care learners’ feelings. Perception-oriented environments are beneficial for observation. Symbol-oriented environments are particularly useful for thinking, and behavior-oriented environments are beneficial for doing [42]. The real clinical environments are the immediate context in which a connection is needed between learning and practice. The real clinical environment is the anchor and scaffold upon which learners are encouraged to learn. The real clinical environment includes physical environments and social environments. The content in physical environments, such as patients and their disease, microbiological samples, documentation and clinical notes, medical equipment, drugs,Figure 3. MARE function structure.Zhu et al and consequences of bacterial resistance, can be the anchor to trigger a learning activity, which then aims to fulfill a learning outcome within the appropriate therapeutic stage. The social environment (ie, local culture and customs, organizational norms, and policy) shapes the content and forms of learning, which should be more instrumental or communicative. Virtual environments, which are simulated with computers, extend the real-world environment with an assurance of safety and enable or increase opportunities for engagement. Although it may be necessary or attractive for medical learners to learn in the clinical context, observing a real-wo.

Ctancy of 50, the absolute difference between the two is 20 which represents

Ctancy of 50, the absolute difference between the two is 20 which represents low similarity when compared to the United Kingdom’s life expectancy of 72 for this indicator. In Fig 9, we can observe the variations in similarity for countries with different levels of community multiplexity. What is immediately striking is that countries that share a maximal number of communities and therefore exhibit the greatest community multiplexity, have the Anlotinib chemical information smallest margin of difference across all indicators. This suggests that countries with the PD98059 web highest community multiplexity have a very similar socioeconomic profile. This is confirmed by a two-sample Kolmogorov-Smirnov test between the distributions of differences in each indicator for pairs sharing different numbers of communities. Although the KS statistic is lower between groups sharing 0 and 1 communities (apx. 0.1 for all indicators and p-value <0.01), it is very high for groups between 1 and 6 communities (0.4 and above, p-value <0.01), except for mobile phone penetration (detailed KS test results are presented in S1 Table).PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,15 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 9. Socioeconomic difference margin between countries who share communities in the global flow networks. doi:10.1371/journal.pone.0155976.gFurther to this observation, in most indicators there is a very strong significance in the level of community multiplexity--the higher the community multiplexity index between two countries, the smaller the difference between their socioeconomic profiles. There are notable exceptions to this such as the mobile phone penetration ratio, where it appears that beyond the highest level of multiplexity, all other countries are relatively similar in this aspect with low variation even for those pairs of countries which share no communities. For all other indicators such as GDP, Literacy ratio, HDI and Internet penetration, there is a dramatic increase in similarity past a community multiplexity of 3. Ultimately, these similarities can be used to estimate the wellbeing of countries for which it is unknown but can be estimated from its neighbours.DiscussionBig data is often related to real-time data captured through the Internet or social networks. However, the digital divide makes access to big data insights for development more challenging in the least developed and many developing and emerging countries. Can we rely on other networks to overcome these critical data gaps in view of better measuring and monitoring developmental progress? This is particularly important following the United Nations adoption of the Sustainable Development Goals (SDG) in September 2015, made of 17 goals, 169 targets and almost 200 universal indicators, each of them calling for regular and increasingly disaggregated monitoring in every country during the 2016?0 period. This commitment invites a nuanced discussion on the nature and importance of measurement, inference and triangulation of data sources. This discussion is particularly prescient in the face of complex intertwined developmental challenges in an age of increased globalisation, economic interdependence and climate change. The work presented above has clearly shown the value of measuring, comparing, and combining metrics of global connectivity across six different global networks in order to approximate socioeconomic indicators and to identify network communities.Ctancy of 50, the absolute difference between the two is 20 which represents low similarity when compared to the United Kingdom's life expectancy of 72 for this indicator. In Fig 9, we can observe the variations in similarity for countries with different levels of community multiplexity. What is immediately striking is that countries that share a maximal number of communities and therefore exhibit the greatest community multiplexity, have the smallest margin of difference across all indicators. This suggests that countries with the highest community multiplexity have a very similar socioeconomic profile. This is confirmed by a two-sample Kolmogorov-Smirnov test between the distributions of differences in each indicator for pairs sharing different numbers of communities. Although the KS statistic is lower between groups sharing 0 and 1 communities (apx. 0.1 for all indicators and p-value <0.01), it is very high for groups between 1 and 6 communities (0.4 and above, p-value <0.01), except for mobile phone penetration (detailed KS test results are presented in S1 Table).PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,15 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 9. Socioeconomic difference margin between countries who share communities in the global flow networks. doi:10.1371/journal.pone.0155976.gFurther to this observation, in most indicators there is a very strong significance in the level of community multiplexity--the higher the community multiplexity index between two countries, the smaller the difference between their socioeconomic profiles. There are notable exceptions to this such as the mobile phone penetration ratio, where it appears that beyond the highest level of multiplexity, all other countries are relatively similar in this aspect with low variation even for those pairs of countries which share no communities. For all other indicators such as GDP, Literacy ratio, HDI and Internet penetration, there is a dramatic increase in similarity past a community multiplexity of 3. Ultimately, these similarities can be used to estimate the wellbeing of countries for which it is unknown but can be estimated from its neighbours.DiscussionBig data is often related to real-time data captured through the Internet or social networks. However, the digital divide makes access to big data insights for development more challenging in the least developed and many developing and emerging countries. Can we rely on other networks to overcome these critical data gaps in view of better measuring and monitoring developmental progress? This is particularly important following the United Nations adoption of the Sustainable Development Goals (SDG) in September 2015, made of 17 goals, 169 targets and almost 200 universal indicators, each of them calling for regular and increasingly disaggregated monitoring in every country during the 2016?0 period. This commitment invites a nuanced discussion on the nature and importance of measurement, inference and triangulation of data sources. This discussion is particularly prescient in the face of complex intertwined developmental challenges in an age of increased globalisation, economic interdependence and climate change. The work presented above has clearly shown the value of measuring, comparing, and combining metrics of global connectivity across six different global networks in order to approximate socioeconomic indicators and to identify network communities.

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the PD173074 site bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this GW 4064 cost second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.

‘ coordinate is the percentage of roles (s)he accepted for each

‘ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ order 6-Methoxybaicalein scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. purchase Vadadustat Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.’ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (BL-8040 manufacturer Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent GSK343 site drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

His flexibility in order to achieve certain caregiving ends. Yet this

His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s HIV-1 integrase inhibitor 2 custom synthesis increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an Pyrvinium embonate site integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.

S are different proteins from the corresponding subunits of the PDH

S are different proteins from the corresponding subunits of the PDH complex and are encoded by the sucA and sucB genes, respectively. However, the E3 subunit is the same protein, Lpd, found in the PDH complex. In aerobically grown E. coli, this complex catalyzes a key step in the citric acid cycle and also supplies succinyl-CoA for biosynthesis of two amino acids, methionine and lysine (152). Under the appropriate conditions, E. coli strains lacking functional 2-OGDH can be supplemented with succinate or methionine plus lysine to provide metabolic bypasses of loss of this enzyme complex (152). Expression of the 2-OGDH is highly induced during aerobic growth on acetate and citric acid cycle intermediates and is severely repressed during fermentative growth where succinyl-CoA is generated by succinyl-CoA synthetase (144) although 2-OGDH is synthesized by cells gown in anaerobic media containing an electron acceptor such as nitrate or fumarate (153). Glycine cleavage system The third lipoylated RM-493 web protein of E. coli is the H protein of the glycine cleavage system, an enzyme widely distributed in bacteria and in the mitochondria of plants (where it is 1-Deoxynojirimycin site called glycine decarboxylase), fungi and mammals (154?56). The glycine cleavage system catalyzes the reversible cleavage of glycine, yielding carbon dioxide, ammonia, 5,10methylenetetrahydrofolate plus a reduced pyridine nucleotide. It consists of four component proteins termed the T, H, P and L proteins. The first three proteins are encoded by the gcvT gcvH gcvP operon while L protein is the same as Lpd, the E3 protein of the 2-oxo acid dehydrogenases as discussed above (157). P protein catalyzes the pyridoxal phosphatedependent decarboxylation of glycine and transfers the remaining methylamine moiety to one of the sulfhydryl groups of the lipoyl prosthetic group of H protein. T protein catalyzes the release of ammoniate and transfer of the one-carbon unit to tetrahydrofolate from the lipoyl residue. L protein is a lipoamide dehydrogenase that catalyzes the reoxidation of the dihydrolipoyl residue of H protein and reduction of NAD+. Thus, the lipoic acid moiety of H protein interacts with the active sites of three different enzymes in a manner analogous to that found for 2-oxoacid dehydrogenase complexes.EcoSal Plus. Author manuscript; available in PMC 2015 January 06.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptCronanPageStructures of lipoylated and biotinylated proteinsIn all 2-oxoacid dehydrogenase complexes, the core of the structure is provided by the E2 subunit to which the E1 and E3 components are bound tightly but noncovalently. In the PDH and 2-OGDH complexes of Escherichia coli and other gram-negative bacteria (158, 159) plus the 2-OGDH and branched-chain 2-oxoacid dehydrogenase complexes of mammals (160, 161), the core consists of 24 copies of the E2 chain arranged with octahedral symmetry, whereas in the PDH complexes of mammals and Gram-positive bacteria (162?165), the core comprises 60 E2 chains arranged with icosahedral symmetry. In all 2-oxoacid dehydrogenase complexes, the E2 component has a multi-domain structure comprising (from the N terminus): lipoyl domain (or domains of ca. 9 kDa), a small peripheral subunitbinding domain (ca. 4 kDa) and a much larger catalytic domain (ca 28 kDa) that houses the acyltransferase activity and aggregates to form the inner core of the complexes. These domains are separated by long (25?0 residue) segments of polypeptid.S are different proteins from the corresponding subunits of the PDH complex and are encoded by the sucA and sucB genes, respectively. However, the E3 subunit is the same protein, Lpd, found in the PDH complex. In aerobically grown E. coli, this complex catalyzes a key step in the citric acid cycle and also supplies succinyl-CoA for biosynthesis of two amino acids, methionine and lysine (152). Under the appropriate conditions, E. coli strains lacking functional 2-OGDH can be supplemented with succinate or methionine plus lysine to provide metabolic bypasses of loss of this enzyme complex (152). Expression of the 2-OGDH is highly induced during aerobic growth on acetate and citric acid cycle intermediates and is severely repressed during fermentative growth where succinyl-CoA is generated by succinyl-CoA synthetase (144) although 2-OGDH is synthesized by cells gown in anaerobic media containing an electron acceptor such as nitrate or fumarate (153). Glycine cleavage system The third lipoylated protein of E. coli is the H protein of the glycine cleavage system, an enzyme widely distributed in bacteria and in the mitochondria of plants (where it is called glycine decarboxylase), fungi and mammals (154?56). The glycine cleavage system catalyzes the reversible cleavage of glycine, yielding carbon dioxide, ammonia, 5,10methylenetetrahydrofolate plus a reduced pyridine nucleotide. It consists of four component proteins termed the T, H, P and L proteins. The first three proteins are encoded by the gcvT gcvH gcvP operon while L protein is the same as Lpd, the E3 protein of the 2-oxo acid dehydrogenases as discussed above (157). P protein catalyzes the pyridoxal phosphatedependent decarboxylation of glycine and transfers the remaining methylamine moiety to one of the sulfhydryl groups of the lipoyl prosthetic group of H protein. T protein catalyzes the release of ammoniate and transfer of the one-carbon unit to tetrahydrofolate from the lipoyl residue. L protein is a lipoamide dehydrogenase that catalyzes the reoxidation of the dihydrolipoyl residue of H protein and reduction of NAD+. Thus, the lipoic acid moiety of H protein interacts with the active sites of three different enzymes in a manner analogous to that found for 2-oxoacid dehydrogenase complexes.EcoSal Plus. Author manuscript; available in PMC 2015 January 06.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptCronanPageStructures of lipoylated and biotinylated proteinsIn all 2-oxoacid dehydrogenase complexes, the core of the structure is provided by the E2 subunit to which the E1 and E3 components are bound tightly but noncovalently. In the PDH and 2-OGDH complexes of Escherichia coli and other gram-negative bacteria (158, 159) plus the 2-OGDH and branched-chain 2-oxoacid dehydrogenase complexes of mammals (160, 161), the core consists of 24 copies of the E2 chain arranged with octahedral symmetry, whereas in the PDH complexes of mammals and Gram-positive bacteria (162?165), the core comprises 60 E2 chains arranged with icosahedral symmetry. In all 2-oxoacid dehydrogenase complexes, the E2 component has a multi-domain structure comprising (from the N terminus): lipoyl domain (or domains of ca. 9 kDa), a small peripheral subunitbinding domain (ca. 4 kDa) and a much larger catalytic domain (ca 28 kDa) that houses the acyltransferase activity and aggregates to form the inner core of the complexes. These domains are separated by long (25?0 residue) segments of polypeptid.

Inary levels of discrimination and social, political and economic marginalization, including

Inary levels of discrimination and social, political and economic marginalization, including disease-related social stigma (alleged carriers of HIV/AIDS and tuberculosis) and officially-sanctioned detention (Boswell, 1982; Stepick, 1998). Given these challenging life circumstances, Haitian immigrants are particularly predisposed to draw on the resources and networks found within the church (Stepick, 1998). The present findings of higher rates of church membership, participation in church activities, prayer, and stated importance of children’s religious training among Haitian immigrants are consistent with research demonstrating high levels of service attendance among this group (Stepick, 1998) and the central position of churches in providing social, cultural and community resources (Richmond, 2005; Stepick et al., 2009). A slightly different pattern of findings for persons from Trinidad and Tobago (higher levels of church membership, but lower levels of service attendance) are interesting and require further study. Explanations for the observed significant country of origin differences in religious involvement for immigrants from Haiti and Trinidad and Tobago are multifaceted and complex. Subsequent research on the noted social, cultural, psychological and civicRev Relig Res. I-CBP112 web Author manuscript; available in PMC 2011 December 1.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTaylor et al.Pagefunctions of Caribbean immigrant worship communities can explore in more detail the factors and processes associated with religious expression and involvement.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn conclusion, this is the first paper on the demographic correlates of religious participation among a national sample of Black Carribean adults. The availability of a nationally representative sample of Caribbean Blacks, was a definite advantage of the study and provides an important complement to small and geographically situated ethnographic studies of religious involvement among Black Caribbean communities. Despite these advantages, the findings are limited by restrictions in the sample. The Black Caribbean sample excludes individuals who do not speak English (i.e., persons who only speak Spanish, Haitian-French, or Creole dialects) and, as a consequence, the study findings are not generalizable to these groups of Caribbean Blacks. Nonetheless, the significant advantages of the national probability sample, methods, and analysis provide a unique opportunity to examine demographic differences in religiosity across multiple measures of religious participation. In addition, specific findings for country of origin and immigration status differences suggest important new areas of study for religious involvement among Caribbean Blacks. Taken together, these findings lay the groundwork for future investigations of religious involvement both within this population and in I-CBP112MedChemExpress I-CBP112 comparison to other race, ethnic and immigrant groups.
NIH Public AccessAuthor ManuscriptJ Cogn Dev. Author manuscript; available in PMC 2011 July 7.Published in final edited form as: J Cogn Dev. 2010 ; 11(2): 121?36. doi:10.1080/15248371003699969.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTwelve Frequently Asked Questions About Growth Curve ModelingPatrick J. Curran, Khawla Obeidat, and Diane Losardo University of North Carolina at Chapel HillAbstractLongitudinal data analysis has long played a signifi.Inary levels of discrimination and social, political and economic marginalization, including disease-related social stigma (alleged carriers of HIV/AIDS and tuberculosis) and officially-sanctioned detention (Boswell, 1982; Stepick, 1998). Given these challenging life circumstances, Haitian immigrants are particularly predisposed to draw on the resources and networks found within the church (Stepick, 1998). The present findings of higher rates of church membership, participation in church activities, prayer, and stated importance of children’s religious training among Haitian immigrants are consistent with research demonstrating high levels of service attendance among this group (Stepick, 1998) and the central position of churches in providing social, cultural and community resources (Richmond, 2005; Stepick et al., 2009). A slightly different pattern of findings for persons from Trinidad and Tobago (higher levels of church membership, but lower levels of service attendance) are interesting and require further study. Explanations for the observed significant country of origin differences in religious involvement for immigrants from Haiti and Trinidad and Tobago are multifaceted and complex. Subsequent research on the noted social, cultural, psychological and civicRev Relig Res. Author manuscript; available in PMC 2011 December 1.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTaylor et al.Pagefunctions of Caribbean immigrant worship communities can explore in more detail the factors and processes associated with religious expression and involvement.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn conclusion, this is the first paper on the demographic correlates of religious participation among a national sample of Black Carribean adults. The availability of a nationally representative sample of Caribbean Blacks, was a definite advantage of the study and provides an important complement to small and geographically situated ethnographic studies of religious involvement among Black Caribbean communities. Despite these advantages, the findings are limited by restrictions in the sample. The Black Caribbean sample excludes individuals who do not speak English (i.e., persons who only speak Spanish, Haitian-French, or Creole dialects) and, as a consequence, the study findings are not generalizable to these groups of Caribbean Blacks. Nonetheless, the significant advantages of the national probability sample, methods, and analysis provide a unique opportunity to examine demographic differences in religiosity across multiple measures of religious participation. In addition, specific findings for country of origin and immigration status differences suggest important new areas of study for religious involvement among Caribbean Blacks. Taken together, these findings lay the groundwork for future investigations of religious involvement both within this population and in comparison to other race, ethnic and immigrant groups.
NIH Public AccessAuthor ManuscriptJ Cogn Dev. Author manuscript; available in PMC 2011 July 7.Published in final edited form as: J Cogn Dev. 2010 ; 11(2): 121?36. doi:10.1080/15248371003699969.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTwelve Frequently Asked Questions About Growth Curve ModelingPatrick J. Curran, Khawla Obeidat, and Diane Losardo University of North Carolina at Chapel HillAbstractLongitudinal data analysis has long played a signifi.

Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC

Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC, INBIO, INHS, NMNH). COSTA RICA, ACG database codes: See Appendix 2 for detailed label data. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: tegula pale, humeral complex half pale/half dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body get Cyclosporin A length (head to apex of metasoma): 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Fore wing length: 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.3?.5, rarely 2.0?.2. Interocellar distance/ posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.2?.3. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its Varlitinib chemical information Maximum diameter). Mesoscutellar disc: with punctures near margins, central part mostly smooth. Number of pits in scutoscutellar sulcus: 5 or 6 or 7 or 8. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.4?0.5. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: mostly sculptured. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 2.8?.1. Mediotergite 2 sculpture: mostly smooth. Outer margin of hypopygium: with a wide, medially folded,Review of Apanteles sensu stricto (Hymenoptera, Braconidae, Microgastrinae)…transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.6?.7, rarely 1.2?.3. Length of fore wing veins r/2RS: 1.7?.9. Length of fore wing veins 2RS/2M: 0.9?.0. Length of fore wing veins 2M/(RS+M)b: 0.9?.0. Pterostigma length/width: 3.6 or more. Point of insertion of vein r in pterostigma: clearly beyond half way point length of pterostigma. Angle of vein r with fore wing anterior margin: clearly outwards, inclined towards fore wing apex. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. As in female but with darker legs and smoother mediotergite 1. Molecular data. Sequences in BOLD:.Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC, INBIO, INHS, NMNH). COSTA RICA, ACG database codes: See Appendix 2 for detailed label data. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: tegula pale, humeral complex half pale/half dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Fore wing length: 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.3?.5, rarely 2.0?.2. Interocellar distance/ posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.2?.3. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with punctures near margins, central part mostly smooth. Number of pits in scutoscutellar sulcus: 5 or 6 or 7 or 8. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.4?0.5. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: mostly sculptured. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 2.8?.1. Mediotergite 2 sculpture: mostly smooth. Outer margin of hypopygium: with a wide, medially folded,Review of Apanteles sensu stricto (Hymenoptera, Braconidae, Microgastrinae)…transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.6?.7, rarely 1.2?.3. Length of fore wing veins r/2RS: 1.7?.9. Length of fore wing veins 2RS/2M: 0.9?.0. Length of fore wing veins 2M/(RS+M)b: 0.9?.0. Pterostigma length/width: 3.6 or more. Point of insertion of vein r in pterostigma: clearly beyond half way point length of pterostigma. Angle of vein r with fore wing anterior margin: clearly outwards, inclined towards fore wing apex. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. As in female but with darker legs and smoother mediotergite 1. Molecular data. Sequences in BOLD:.

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the buy CEP-37440 possibility of selection acting on a GW0742 site single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. PM01183 biological activity Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering UNC0642 molecular weight Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

His flexibility in order to achieve certain caregiving ends. Yet this

His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while LY317615 web children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the Aviptadil chemical information patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data MonocrotalineMedChemExpress Crotaline analysis sufficiently Cyclopamine web rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 4-Deoxyuridine manufacturer galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox Mirogabalin chemical information chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.

Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and

Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and the case photographs of the same men housed in the Gillies Archives at Queen Mary’s Hospital in Sidcup. Tonks regarded his surgical studies as “rather dreadful subjects for the public view” (n.p.) and complained of “all the more tedious visitors” to the hospital for whom the drawings were one of the “sights” (Hone, 128). In recent years, though, the portraits have found a wider audience. They have been exhibited at the Venice Biennale, Tate Britain, the Science Museum in London, the Hunterian Museum at the Royal College of Surgeons of England, the Wellcome Collection, University College London, and the National Army Museum in Chelsea. In June 2007 the full series was made digitally available on the website of the Gillies Archives,4 and Pat Barker has spoken of them as a source of inspiration for her new novel Toby’s Room.5 The photographs of Gillies’ patients have entered the public domain alongside the drawings. A selection of complete case files from the Gillies Archives can be viewed online as part of the Wellcome-funded Sci-Art collaboration, Project Fa de, and case photographs have featured in several recent exhibitions including Faces of Battle at the National Army Museum and War and Medicine at the Wellcome.6 Even more than the drawings, the photographs question the limits and propriety of spectatorship. At least with the pastels, one is aware — almost physically — of Tonks’ attentiveness, the qualityM E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 1 Photograph of Henry Tonks in his room at The Queen’s Hospital, Sidcup, 1917.P H OTO G R AP H I E SFIGURE 2 Horace Nicholls, Repairing War’s Ravages: Renovating facial injuries. Captain Derwent Wood painting the plate. Imperial War Museum, Q.30.457. ?IWM.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R Eof the artist’s touch and the duration of his gaze. His authority, as an artist and surgeon, licenses our own interest. The photographs appear unmediated by any aesthetic concerns: physically and psychologically naked. When I teach this material (usually to history of art students), I tend not to use the most harrowing images of facial injury and reconstructive surgery. Apart from my own discomfort, I worry how my students will respond: with pity? With disgust? Fascination? Should I name the patient, or protect his anonymity? Would he, or his relatives, want the photograph to be shown in a non-medical context? Is there a happy ending — a redemptive “after surgery” to counterbalance the “before”? These questions might give me pause for thought, but they generally remain unspoken. Here, though, I have chosen one image precisely because it confronts the interested, curious or appalled viewer with the problematic nature of spectatorship and empathy. In an interview with Marq Smith, W.J.T. Mitchell speculated that “the most interesting new questions for visual studies . . . will be located at the frontiers of visuality, the places where seeing approaches a limit” (36). I would suggest that medical images are one such frontier: an ethical borderland in which legal definitions of privacy, RWJ 64809MedChemExpress SB 203580 personhood and human rights compete with the contemporary politics of witnessing, memory and RP5264 supplier memorialisation; a space of fantasy where fascination and aversion are found in equal measure. The photograph in question (Figure 3) is a pre-operative record of one of Gillies’ patients, who was also draw.Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and the case photographs of the same men housed in the Gillies Archives at Queen Mary’s Hospital in Sidcup. Tonks regarded his surgical studies as “rather dreadful subjects for the public view” (n.p.) and complained of “all the more tedious visitors” to the hospital for whom the drawings were one of the “sights” (Hone, 128). In recent years, though, the portraits have found a wider audience. They have been exhibited at the Venice Biennale, Tate Britain, the Science Museum in London, the Hunterian Museum at the Royal College of Surgeons of England, the Wellcome Collection, University College London, and the National Army Museum in Chelsea. In June 2007 the full series was made digitally available on the website of the Gillies Archives,4 and Pat Barker has spoken of them as a source of inspiration for her new novel Toby’s Room.5 The photographs of Gillies’ patients have entered the public domain alongside the drawings. A selection of complete case files from the Gillies Archives can be viewed online as part of the Wellcome-funded Sci-Art collaboration, Project Fa de, and case photographs have featured in several recent exhibitions including Faces of Battle at the National Army Museum and War and Medicine at the Wellcome.6 Even more than the drawings, the photographs question the limits and propriety of spectatorship. At least with the pastels, one is aware — almost physically — of Tonks’ attentiveness, the qualityM E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 1 Photograph of Henry Tonks in his room at The Queen’s Hospital, Sidcup, 1917.P H OTO G R AP H I E SFIGURE 2 Horace Nicholls, Repairing War’s Ravages: Renovating facial injuries. Captain Derwent Wood painting the plate. Imperial War Museum, Q.30.457. ?IWM.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R Eof the artist’s touch and the duration of his gaze. His authority, as an artist and surgeon, licenses our own interest. The photographs appear unmediated by any aesthetic concerns: physically and psychologically naked. When I teach this material (usually to history of art students), I tend not to use the most harrowing images of facial injury and reconstructive surgery. Apart from my own discomfort, I worry how my students will respond: with pity? With disgust? Fascination? Should I name the patient, or protect his anonymity? Would he, or his relatives, want the photograph to be shown in a non-medical context? Is there a happy ending — a redemptive “after surgery” to counterbalance the “before”? These questions might give me pause for thought, but they generally remain unspoken. Here, though, I have chosen one image precisely because it confronts the interested, curious or appalled viewer with the problematic nature of spectatorship and empathy. In an interview with Marq Smith, W.J.T. Mitchell speculated that “the most interesting new questions for visual studies . . . will be located at the frontiers of visuality, the places where seeing approaches a limit” (36). I would suggest that medical images are one such frontier: an ethical borderland in which legal definitions of privacy, personhood and human rights compete with the contemporary politics of witnessing, memory and memorialisation; a space of fantasy where fascination and aversion are found in equal measure. The photograph in question (Figure 3) is a pre-operative record of one of Gillies’ patients, who was also draw.

Ctancy of 50, the absolute difference between the two is 20 which represents

Ctancy of 50, the absolute difference between the two is 20 which represents low similarity when compared to the United Kingdom’s life expectancy of 72 for this indicator. In Fig 9, we can observe the variations in similarity for countries with different levels of community multiplexity. What is immediately striking is that countries that share a maximal number of MLN9708 web communities and therefore exhibit the greatest community multiplexity, have the smallest margin of difference across all indicators. This suggests that countries with the highest community multiplexity have a very similar socioeconomic profile. This is confirmed by a Rocaglamide A web two-sample Kolmogorov-Smirnov test between the distributions of differences in each indicator for pairs sharing different numbers of communities. Although the KS statistic is lower between groups sharing 0 and 1 communities (apx. 0.1 for all indicators and p-value <0.01), it is very high for groups between 1 and 6 communities (0.4 and above, p-value <0.01), except for mobile phone penetration (detailed KS test results are presented in S1 Table).PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,15 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 9. Socioeconomic difference margin between countries who share communities in the global flow networks. doi:10.1371/journal.pone.0155976.gFurther to this observation, in most indicators there is a very strong significance in the level of community multiplexity--the higher the community multiplexity index between two countries, the smaller the difference between their socioeconomic profiles. There are notable exceptions to this such as the mobile phone penetration ratio, where it appears that beyond the highest level of multiplexity, all other countries are relatively similar in this aspect with low variation even for those pairs of countries which share no communities. For all other indicators such as GDP, Literacy ratio, HDI and Internet penetration, there is a dramatic increase in similarity past a community multiplexity of 3. Ultimately, these similarities can be used to estimate the wellbeing of countries for which it is unknown but can be estimated from its neighbours.DiscussionBig data is often related to real-time data captured through the Internet or social networks. However, the digital divide makes access to big data insights for development more challenging in the least developed and many developing and emerging countries. Can we rely on other networks to overcome these critical data gaps in view of better measuring and monitoring developmental progress? This is particularly important following the United Nations adoption of the Sustainable Development Goals (SDG) in September 2015, made of 17 goals, 169 targets and almost 200 universal indicators, each of them calling for regular and increasingly disaggregated monitoring in every country during the 2016?0 period. This commitment invites a nuanced discussion on the nature and importance of measurement, inference and triangulation of data sources. This discussion is particularly prescient in the face of complex intertwined developmental challenges in an age of increased globalisation, economic interdependence and climate change. The work presented above has clearly shown the value of measuring, comparing, and combining metrics of global connectivity across six different global networks in order to approximate socioeconomic indicators and to identify network communities.Ctancy of 50, the absolute difference between the two is 20 which represents low similarity when compared to the United Kingdom's life expectancy of 72 for this indicator. In Fig 9, we can observe the variations in similarity for countries with different levels of community multiplexity. What is immediately striking is that countries that share a maximal number of communities and therefore exhibit the greatest community multiplexity, have the smallest margin of difference across all indicators. This suggests that countries with the highest community multiplexity have a very similar socioeconomic profile. This is confirmed by a two-sample Kolmogorov-Smirnov test between the distributions of differences in each indicator for pairs sharing different numbers of communities. Although the KS statistic is lower between groups sharing 0 and 1 communities (apx. 0.1 for all indicators and p-value <0.01), it is very high for groups between 1 and 6 communities (0.4 and above, p-value <0.01), except for mobile phone penetration (detailed KS test results are presented in S1 Table).PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,15 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 9. Socioeconomic difference margin between countries who share communities in the global flow networks. doi:10.1371/journal.pone.0155976.gFurther to this observation, in most indicators there is a very strong significance in the level of community multiplexity--the higher the community multiplexity index between two countries, the smaller the difference between their socioeconomic profiles. There are notable exceptions to this such as the mobile phone penetration ratio, where it appears that beyond the highest level of multiplexity, all other countries are relatively similar in this aspect with low variation even for those pairs of countries which share no communities. For all other indicators such as GDP, Literacy ratio, HDI and Internet penetration, there is a dramatic increase in similarity past a community multiplexity of 3. Ultimately, these similarities can be used to estimate the wellbeing of countries for which it is unknown but can be estimated from its neighbours.DiscussionBig data is often related to real-time data captured through the Internet or social networks. However, the digital divide makes access to big data insights for development more challenging in the least developed and many developing and emerging countries. Can we rely on other networks to overcome these critical data gaps in view of better measuring and monitoring developmental progress? This is particularly important following the United Nations adoption of the Sustainable Development Goals (SDG) in September 2015, made of 17 goals, 169 targets and almost 200 universal indicators, each of them calling for regular and increasingly disaggregated monitoring in every country during the 2016?0 period. This commitment invites a nuanced discussion on the nature and importance of measurement, inference and triangulation of data sources. This discussion is particularly prescient in the face of complex intertwined developmental challenges in an age of increased globalisation, economic interdependence and climate change. The work presented above has clearly shown the value of measuring, comparing, and combining metrics of global connectivity across six different global networks in order to approximate socioeconomic indicators and to identify network communities.

N scan or take a photo of the object in their

N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of SCR7 supplement antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a SCR7MedChemExpress SCR7 prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known

.pone.0119985.gAs expected, childhood SCH 530348 site maltreatment was WP1066MedChemExpress WP1066 associated with several covariates known to be related to BMI (Table 3). Some covariates such as unemployment and smoking have been shown in the literature to be negatively associated with BMI, e.g. on average, smokers have a lower BMI [11]. In our study such characteristics were more common among maltreated groups: e.g., prevalence of smoking and unemployment 23y to 50y was higher in the maltreated than nonmaltreated (Table 3). Potentially, these differences would lower the adult BMI among those exposed to childhood maltreatment. Allowance for such factors and their changes over time, as well as other covariates, is important for understanding associations with BMI at specific ages and BMI trajectories. Modelled lifetime trajectories of zBMI and obesity risk (Table 4 and S2 Table) confirmed the patterns with age suggested by simple analyses.Childhood abuseIn both genders there was a positive linear association between zBMI gain with age and physical abuse, by 0.006/y (males) and 0.007/y (females) after adjustment for all covariatesPLOS ONE | DOI:10.1371/journal.pone.0119985 March 26,7 /Child Maltreatment and BMI TrajectoriesTable 3. Characteristics of those with no childhood maltreatment and those abused or neglected ( ). Abuse Non-maltreated Males

T are adaptive (Nelson and Guyer, 2011; Crone and Dahl, 2012). In other

T are adaptive (Nelson and Guyer, 2011; Crone and Dahl, 2012). In other words, adolescents might engage in risk taking to impress peers and achieve or maintain higher social status, instead of risk taking resulting from a lack in the ability to regulate their socially induced AKB-6548MedChemExpress AKB-6548 emotional tendencies. Indeed, the importance of social status, relative to other domains, peaks during early adolescence (LaFontana and Cillessen, 2010). Furthermore, results of a longitudinal study among high school students showed that engaging in smoking behavior in tenth grade led to increased social status over time (Mayeux et al., 2008). Together, these findings suggest that adolescence is a time in development during which individuals engage in risk taking as a form of status-seeking behavior. Moreover, a common (neural) mechanism may underlie the motivation to achieve higher social status and to engage in risk taking (Bhanji and Delgado, 2014). One model for understanding the possible links between status-seeking and risk-taking tendencies in adolescence focuses on pubertal changes in social and affective valuation (Nelson et al., 2005; Forbes and Dahl, 2010; Crone and Dahl, 2012). Specifically, hormonal changes might promote adaptive tendencies for youth to explore ways to ��-Amatoxin web enhance status (i.e. to find a niche that provides admiration). Indeed, the rise in testosterone and estradiol during puberty is thought to reorganize the adolescent brain (Sisk and Zehr, 2005; Schulz et al., 2009) andimpact social behaviors (Schulz and Sisk, 2006; Forbes and Dahl, 2010) as well as risk taking (Peper and Dahl, 2013). Previous studies in adults have shown that testosterone is involved in the attainment and maintenance of social status (Eisenegger et al., 2011; Terburg and Van Honk, 2013). For example, a study using a multi-player auction task in young adult men showed that higher levels of testosterone corresponded with a willingness to incur monetary losses by overbidding, for the sake of winning the auction (Van den Bos et al., 2013). Less is known about the role of estradiol in status-seeking behavior, although existing findings in female adults suggest that estradiol leads to behaviors that augment social status, particularly in women who are competing with other women (Knight and Mehta, 2014). Together, these findings suggest that the rise in testosterone and estradiol during puberty may play a role in enhancing status-relevant information, which in turn may increase statusseeking behaviors, such as risk taking, across adolescence. In this study, we set out to investigate the role of pubertal hormones (testosterone and estradiol) in social influences on adolescent risky decisions and associated reward-related brain processes. To maximize the variance of our pubertal measures while keeping age relatively constant, we recruited participants around the onset of puberty. In this early adolescent sample, we tested whether information about one’s social status in the form of social rank performance feedback compared to monetary performance feedback differentially influenced risk taking and/or reward processing. In keeping with current understandings of the neural networks involved in social cognition in adolescence (reviewed in Blakemore, 2008), multiple brain regions might differentiate these feedback conditions. In particular, sensitivity to the presence of social hierarchies engages the dorsal anterior cingulate and insular cortices (reviewed in Chiao, 2010), which, alo.T are adaptive (Nelson and Guyer, 2011; Crone and Dahl, 2012). In other words, adolescents might engage in risk taking to impress peers and achieve or maintain higher social status, instead of risk taking resulting from a lack in the ability to regulate their socially induced emotional tendencies. Indeed, the importance of social status, relative to other domains, peaks during early adolescence (LaFontana and Cillessen, 2010). Furthermore, results of a longitudinal study among high school students showed that engaging in smoking behavior in tenth grade led to increased social status over time (Mayeux et al., 2008). Together, these findings suggest that adolescence is a time in development during which individuals engage in risk taking as a form of status-seeking behavior. Moreover, a common (neural) mechanism may underlie the motivation to achieve higher social status and to engage in risk taking (Bhanji and Delgado, 2014). One model for understanding the possible links between status-seeking and risk-taking tendencies in adolescence focuses on pubertal changes in social and affective valuation (Nelson et al., 2005; Forbes and Dahl, 2010; Crone and Dahl, 2012). Specifically, hormonal changes might promote adaptive tendencies for youth to explore ways to enhance status (i.e. to find a niche that provides admiration). Indeed, the rise in testosterone and estradiol during puberty is thought to reorganize the adolescent brain (Sisk and Zehr, 2005; Schulz et al., 2009) andimpact social behaviors (Schulz and Sisk, 2006; Forbes and Dahl, 2010) as well as risk taking (Peper and Dahl, 2013). Previous studies in adults have shown that testosterone is involved in the attainment and maintenance of social status (Eisenegger et al., 2011; Terburg and Van Honk, 2013). For example, a study using a multi-player auction task in young adult men showed that higher levels of testosterone corresponded with a willingness to incur monetary losses by overbidding, for the sake of winning the auction (Van den Bos et al., 2013). Less is known about the role of estradiol in status-seeking behavior, although existing findings in female adults suggest that estradiol leads to behaviors that augment social status, particularly in women who are competing with other women (Knight and Mehta, 2014). Together, these findings suggest that the rise in testosterone and estradiol during puberty may play a role in enhancing status-relevant information, which in turn may increase statusseeking behaviors, such as risk taking, across adolescence. In this study, we set out to investigate the role of pubertal hormones (testosterone and estradiol) in social influences on adolescent risky decisions and associated reward-related brain processes. To maximize the variance of our pubertal measures while keeping age relatively constant, we recruited participants around the onset of puberty. In this early adolescent sample, we tested whether information about one’s social status in the form of social rank performance feedback compared to monetary performance feedback differentially influenced risk taking and/or reward processing. In keeping with current understandings of the neural networks involved in social cognition in adolescence (reviewed in Blakemore, 2008), multiple brain regions might differentiate these feedback conditions. In particular, sensitivity to the presence of social hierarchies engages the dorsal anterior cingulate and insular cortices (reviewed in Chiao, 2010), which, alo.

A six-min incubation with Gentle Cell Dissociation Reagent followed by complete

A six-min incubation with Gentle Cell Dissociation Reagent followed by complete physical dispersions by repeated pipetting. Large cells (>70 m) were then collected by Necrosulfonamide manufacturer passing the suspension successively ONO-4059 web through a series of nylon cell strainers (70 m and 40 m, Fisher Scientific) to generate three cell size fractions (>70 m, 40?0 m, and <40 m). The captured cells on the strainer were recovered by inverting the strainer and rinsing with culture medium. Similarly, middle size cells (40?0 m) were obtained from the <70-m fraction by collection on a 40-m cell strainer after removal of <70-m cells. The three size fractions were used in all subsequent analyses. Portions of the size-fractioned cells were fixed in 4 (vol/vol) paraformaldehyde/PBS solution for 15 min and resuspended (5.0 ?102 and 1.0 ?105 cells/100 L PBS). The suspensions were loaded into a Shandon single cytofunnel and centrifuged for 5 min at 1,000 ?g in a Shandon CytoSpin 4 cytocentrifuge (Thermo Scientific). Derivation Primary Human PHTu and PHTd. Placental tissue samples were collected by the Obstetrical Specimen Procurement Unit at Magee-Womens Hospital of the University of Pittsburgh Medical Center. The work was performed under an exempt protocol approved by the Institutional Review Board (IRB) at the University of Pittsburgh. Under the protocol, patients provided written consent for the use of deidentified discarded tissues for research upon admittance to the hospital. Primary villous PHTs were derived and cultured according to published procedures (12, 49, 50) from three term human placentas (one female and two males). Multiple primary cultures were established from each placenta at a density of 3.5 ?105 cells/cm2 in DMEM supplemented with 10 (vol/vol) FBS and antibiotics under a 5 (vol/vol) CO2/air atmosphere at 37 . Triplicate cultures from each placenta were harvested at 9 h (PHTu) before syncytium formation and subsequently at 48 h (PHTd) when syncytium formation had occurred. The sieving technique used for the hESC-derived cells was thus unnecessary for the term placental STB. Total RNA was extracted from each sample (3 ?3 at 9 h and 48 h, respectively) to provide a total of 18 samples for RNA-seq analysis. Additional methods are described in SI Appendix, SI Materials and Methods. ACKNOWLEDGMENTS. We thank L. C. Schulz for her critical reading of the manuscript and her helpful comments; N. J. Bivens for RNA-seq; W. Spollen, C. Bottoms, and S. Givan for their sequence data analysis; Y. Tian for immunoassays; A. Jurkevich for technical assistance; M. Schauflinger, D. Grant, and T. A. White for sharing equipment; and D. F. Reith for his editorial assistance and administrative support. This study was supported by NIH Grant R01HD077108 (to T.E. and D.J.S.) and Grant R01HD067759 (to R.M.R.).7. Loke YW, King A (1995) Human Implantation: Cell Biology and Immunology (Cambridge Univ Press, Cambridge). 8. Miller RK, et al. (2005) Human placental explants in culture: Approaches and assessments. Placenta 26(6):439?48. 9. Sim CM, Sibley CP, Jones CJ, Turner MA, Greenwood SL (2001) The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am J Physiol Regul Integr Comp Physiol 280(4):R1116 1122. 10. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186(2):306?16. 11. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B (2010) The choriocarcinoma cell line BeW.A six-min incubation with Gentle Cell Dissociation Reagent followed by complete physical dispersions by repeated pipetting. Large cells (>70 m) were then collected by passing the suspension successively through a series of nylon cell strainers (70 m and 40 m, Fisher Scientific) to generate three cell size fractions (>70 m, 40?0 m, and <40 m). The captured cells on the strainer were recovered by inverting the strainer and rinsing with culture medium. Similarly, middle size cells (40?0 m) were obtained from the <70-m fraction by collection on a 40-m cell strainer after removal of <70-m cells. The three size fractions were used in all subsequent analyses. Portions of the size-fractioned cells were fixed in 4 (vol/vol) paraformaldehyde/PBS solution for 15 min and resuspended (5.0 ?102 and 1.0 ?105 cells/100 L PBS). The suspensions were loaded into a Shandon single cytofunnel and centrifuged for 5 min at 1,000 ?g in a Shandon CytoSpin 4 cytocentrifuge (Thermo Scientific). Derivation Primary Human PHTu and PHTd. Placental tissue samples were collected by the Obstetrical Specimen Procurement Unit at Magee-Womens Hospital of the University of Pittsburgh Medical Center. The work was performed under an exempt protocol approved by the Institutional Review Board (IRB) at the University of Pittsburgh. Under the protocol, patients provided written consent for the use of deidentified discarded tissues for research upon admittance to the hospital. Primary villous PHTs were derived and cultured according to published procedures (12, 49, 50) from three term human placentas (one female and two males). Multiple primary cultures were established from each placenta at a density of 3.5 ?105 cells/cm2 in DMEM supplemented with 10 (vol/vol) FBS and antibiotics under a 5 (vol/vol) CO2/air atmosphere at 37 . Triplicate cultures from each placenta were harvested at 9 h (PHTu) before syncytium formation and subsequently at 48 h (PHTd) when syncytium formation had occurred. The sieving technique used for the hESC-derived cells was thus unnecessary for the term placental STB. Total RNA was extracted from each sample (3 ?3 at 9 h and 48 h, respectively) to provide a total of 18 samples for RNA-seq analysis. Additional methods are described in SI Appendix, SI Materials and Methods. ACKNOWLEDGMENTS. We thank L. C. Schulz for her critical reading of the manuscript and her helpful comments; N. J. Bivens for RNA-seq; W. Spollen, C. Bottoms, and S. Givan for their sequence data analysis; Y. Tian for immunoassays; A. Jurkevich for technical assistance; M. Schauflinger, D. Grant, and T. A. White for sharing equipment; and D. F. Reith for his editorial assistance and administrative support. This study was supported by NIH Grant R01HD077108 (to T.E. and D.J.S.) and Grant R01HD067759 (to R.M.R.).7. Loke YW, King A (1995) Human Implantation: Cell Biology and Immunology (Cambridge Univ Press, Cambridge). 8. Miller RK, et al. (2005) Human placental explants in culture: Approaches and assessments. Placenta 26(6):439?48. 9. Sim CM, Sibley CP, Jones CJ, Turner MA, Greenwood SL (2001) The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am J Physiol Regul Integr Comp Physiol 280(4):R1116 1122. 10. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186(2):306?16. 11. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B (2010) The choriocarcinoma cell line BeW.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive GSK343MedChemExpress GSK343 effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent Aprotinin chemical information alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

His flexibility in order to achieve certain caregiving ends. Yet this

His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and HMPL-013 chemical information ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal Lasalocid (sodium)MedChemExpress Lasalocid (sodium) system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the 11-DeoxojervineMedChemExpress Cyclopamine method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (R1503 side effects triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.

Preservation (butylated hydroxytoluene).112 The coverage in this section is not intended

Preservation (butylated hydroxytoluene).112 The coverage in this section is not intended to be complete, but is rather focused on representative cases where there are extensive pKa, E, and bond strength data. A reader interested in a particular substituted derivative that does not appear in Table 4 is encouraged to check the references cited there, and reference 56, as many of the primary papers cover a range of substituents.NIH-PA Author MGCD516 chemical information Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Page5.2.1 Phenol (PhOH)–Phenol has been widely studied as the simplest of the aromatic hydroxylic compounds. The gas-phase O BDE in phenol has been a subject of much discussion.62,113,114 Heats of formation from the NIST Chemistry WebBook, Hf as(PhO? = 13 ?1 kcal mol- and Hf as(PhOH =-23.03 ?0.14 kcal mol-1, give BDEg(PhOH) = 88.0 ?1 kcal mol-1.49,70 This value is in between alternative values of 86.7 kcal mol-1 114 and 88.7 kcal mol-1.62 A clearer value for this important benchmark compound would be valuable. A wealth of thermochemical data is available for phenols, in particular their acidity [pKa(ArOH)] and the phenoxyl radical/phenoxide reduction [E?ArO?-)]. Protonated phenoxyl radicals are typically high energy species with aqueous pKa values > 0.115 The most extensive studies of E?ArO?-) are by Bordwell et al. for DMSO solutions116 and by Lind et al. and Steenken and Neta in aqueous media.117,118 The aqueous measurements take advantage of the phenol potential becoming independent of pH above its pKa (see Section 3.2 above). Phenols readily react by hydrogen atom transfer (HAT) and this pathway is implicated in the antioxidant properties of phenols both in vivo and in vitro (see below).119 For the more acidic phenols, or under basic conditions, a mechanism of sequential proton loss then electron transfer (SPLET) can occur.11?213 It is less common for phenols to react by initial outer-sphere electron transfer because of the high E?PhOH?/0) potentials. The ArO? ArOH potentials (or, better, BDFEs) are often above the thermodynamic requirement for water oxidation, as is necessary for the function of Tyrosine Z in photosystem II, mediating hole transfer from the chlorophyll radical cation to the oxygen evolving complex. 5.2.2 2,4,6-Tri-tert-butylphenol (tBu3PhOH)–4-Substituted-2,6-di-tert-butyl-phenols are widely used in the research lab and as food preservatives, especially `butylated hydroxytoluene’ (BHT, 4-Me) and `butylated hydroxyanisole’ (BHA, 4-MeO). 2,4,6-tBu3PhOH is an especially interesting and useful reagent for studies of PCET reactions because of the exceptional stability of the phenoxyl radical (Luteolin 7-glucoside site tBu3PhO?.120 The radical is easily prepared from the corresponding phenol using NaOH and K3Fe(CN)6, and can be isolated as dark blue crystals.120 As discussed for TEMPOH above, we have recently reevaluated the solution BDE of tBu3PhO?in C6H6 to account for recent revision of the thermochemistry of the originally used diphenylhydrazine/azobenzene couple.40 Our preferred value is 81.6 ?0.4 kcal mol-1. The tBu3PhO(?H) PCET couple is a very useful benchmark for the determination of bonds strengths in other phenols. The clearest example is Pedulli and co-workers’ EPR method to measure equilibrium constants for ArOH + tBu3PhO?121 Please note that here and in Table 4, we have slightly adjusted Pedulli’s reported BDEs to reflect our recent critical evaluation of the BDE.Preservation (butylated hydroxytoluene).112 The coverage in this section is not intended to be complete, but is rather focused on representative cases where there are extensive pKa, E, and bond strength data. A reader interested in a particular substituted derivative that does not appear in Table 4 is encouraged to check the references cited there, and reference 56, as many of the primary papers cover a range of substituents.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Page5.2.1 Phenol (PhOH)–Phenol has been widely studied as the simplest of the aromatic hydroxylic compounds. The gas-phase O BDE in phenol has been a subject of much discussion.62,113,114 Heats of formation from the NIST Chemistry WebBook, Hf as(PhO? = 13 ?1 kcal mol- and Hf as(PhOH =-23.03 ?0.14 kcal mol-1, give BDEg(PhOH) = 88.0 ?1 kcal mol-1.49,70 This value is in between alternative values of 86.7 kcal mol-1 114 and 88.7 kcal mol-1.62 A clearer value for this important benchmark compound would be valuable. A wealth of thermochemical data is available for phenols, in particular their acidity [pKa(ArOH)] and the phenoxyl radical/phenoxide reduction [E?ArO?-)]. Protonated phenoxyl radicals are typically high energy species with aqueous pKa values > 0.115 The most extensive studies of E?ArO?-) are by Bordwell et al. for DMSO solutions116 and by Lind et al. and Steenken and Neta in aqueous media.117,118 The aqueous measurements take advantage of the phenol potential becoming independent of pH above its pKa (see Section 3.2 above). Phenols readily react by hydrogen atom transfer (HAT) and this pathway is implicated in the antioxidant properties of phenols both in vivo and in vitro (see below).119 For the more acidic phenols, or under basic conditions, a mechanism of sequential proton loss then electron transfer (SPLET) can occur.11?213 It is less common for phenols to react by initial outer-sphere electron transfer because of the high E?PhOH?/0) potentials. The ArO? ArOH potentials (or, better, BDFEs) are often above the thermodynamic requirement for water oxidation, as is necessary for the function of Tyrosine Z in photosystem II, mediating hole transfer from the chlorophyll radical cation to the oxygen evolving complex. 5.2.2 2,4,6-Tri-tert-butylphenol (tBu3PhOH)–4-Substituted-2,6-di-tert-butyl-phenols are widely used in the research lab and as food preservatives, especially `butylated hydroxytoluene’ (BHT, 4-Me) and `butylated hydroxyanisole’ (BHA, 4-MeO). 2,4,6-tBu3PhOH is an especially interesting and useful reagent for studies of PCET reactions because of the exceptional stability of the phenoxyl radical (tBu3PhO?.120 The radical is easily prepared from the corresponding phenol using NaOH and K3Fe(CN)6, and can be isolated as dark blue crystals.120 As discussed for TEMPOH above, we have recently reevaluated the solution BDE of tBu3PhO?in C6H6 to account for recent revision of the thermochemistry of the originally used diphenylhydrazine/azobenzene couple.40 Our preferred value is 81.6 ?0.4 kcal mol-1. The tBu3PhO(?H) PCET couple is a very useful benchmark for the determination of bonds strengths in other phenols. The clearest example is Pedulli and co-workers’ EPR method to measure equilibrium constants for ArOH + tBu3PhO?121 Please note that here and in Table 4, we have slightly adjusted Pedulli’s reported BDEs to reflect our recent critical evaluation of the BDE.

Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and

Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and the case photographs of the same men order PD168393 housed in the Gillies Archives at Queen Mary’s Hospital in Sidcup. Tonks regarded his surgical studies as “rather dreadful subjects for the public view” (n.p.) and complained of “all the more tedious visitors” to the hospital for whom the drawings were one of the “sights” (Hone, 128). In recent years, though, the portraits have found a wider audience. They have been exhibited at the get LOXO-101 Venice Biennale, Tate Britain, the Science Museum in London, the Hunterian Museum at the Royal College of Surgeons of England, the Wellcome Collection, University College London, and the National Army Museum in Chelsea. In June 2007 the full series was made digitally available on the website of the Gillies Archives,4 and Pat Barker has spoken of them as a source of inspiration for her new novel Toby’s Room.5 The photographs of Gillies’ patients have entered the public domain alongside the drawings. A selection of complete case files from the Gillies Archives can be viewed online as part of the Wellcome-funded Sci-Art collaboration, Project Fa de, and case photographs have featured in several recent exhibitions including Faces of Battle at the National Army Museum and War and Medicine at the Wellcome.6 Even more than the drawings, the photographs question the limits and propriety of spectatorship. At least with the pastels, one is aware — almost physically — of Tonks’ attentiveness, the qualityM E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 1 Photograph of Henry Tonks in his room at The Queen’s Hospital, Sidcup, 1917.P H OTO G R AP H I E SFIGURE 2 Horace Nicholls, Repairing War’s Ravages: Renovating facial injuries. Captain Derwent Wood painting the plate. Imperial War Museum, Q.30.457. ?IWM.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R Eof the artist’s touch and the duration of his gaze. His authority, as an artist and surgeon, licenses our own interest. The photographs appear unmediated by any aesthetic concerns: physically and psychologically naked. When I teach this material (usually to history of art students), I tend not to use the most harrowing images of facial injury and reconstructive surgery. Apart from my own discomfort, I worry how my students will respond: with pity? With disgust? Fascination? Should I name the patient, or protect his anonymity? Would he, or his relatives, want the photograph to be shown in a non-medical context? Is there a happy ending — a redemptive “after surgery” to counterbalance the “before”? These questions might give me pause for thought, but they generally remain unspoken. Here, though, I have chosen one image precisely because it confronts the interested, curious or appalled viewer with the problematic nature of spectatorship and empathy. In an interview with Marq Smith, W.J.T. Mitchell speculated that “the most interesting new questions for visual studies . . . will be located at the frontiers of visuality, the places where seeing approaches a limit” (36). I would suggest that medical images are one such frontier: an ethical borderland in which legal definitions of privacy, personhood and human rights compete with the contemporary politics of witnessing, memory and memorialisation; a space of fantasy where fascination and aversion are found in equal measure. The photograph in question (Figure 3) is a pre-operative record of one of Gillies’ patients, who was also draw.Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and the case photographs of the same men housed in the Gillies Archives at Queen Mary’s Hospital in Sidcup. Tonks regarded his surgical studies as “rather dreadful subjects for the public view” (n.p.) and complained of “all the more tedious visitors” to the hospital for whom the drawings were one of the “sights” (Hone, 128). In recent years, though, the portraits have found a wider audience. They have been exhibited at the Venice Biennale, Tate Britain, the Science Museum in London, the Hunterian Museum at the Royal College of Surgeons of England, the Wellcome Collection, University College London, and the National Army Museum in Chelsea. In June 2007 the full series was made digitally available on the website of the Gillies Archives,4 and Pat Barker has spoken of them as a source of inspiration for her new novel Toby’s Room.5 The photographs of Gillies’ patients have entered the public domain alongside the drawings. A selection of complete case files from the Gillies Archives can be viewed online as part of the Wellcome-funded Sci-Art collaboration, Project Fa de, and case photographs have featured in several recent exhibitions including Faces of Battle at the National Army Museum and War and Medicine at the Wellcome.6 Even more than the drawings, the photographs question the limits and propriety of spectatorship. At least with the pastels, one is aware — almost physically — of Tonks’ attentiveness, the qualityM E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 1 Photograph of Henry Tonks in his room at The Queen’s Hospital, Sidcup, 1917.P H OTO G R AP H I E SFIGURE 2 Horace Nicholls, Repairing War’s Ravages: Renovating facial injuries. Captain Derwent Wood painting the plate. Imperial War Museum, Q.30.457. ?IWM.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R Eof the artist’s touch and the duration of his gaze. His authority, as an artist and surgeon, licenses our own interest. The photographs appear unmediated by any aesthetic concerns: physically and psychologically naked. When I teach this material (usually to history of art students), I tend not to use the most harrowing images of facial injury and reconstructive surgery. Apart from my own discomfort, I worry how my students will respond: with pity? With disgust? Fascination? Should I name the patient, or protect his anonymity? Would he, or his relatives, want the photograph to be shown in a non-medical context? Is there a happy ending — a redemptive “after surgery” to counterbalance the “before”? These questions might give me pause for thought, but they generally remain unspoken. Here, though, I have chosen one image precisely because it confronts the interested, curious or appalled viewer with the problematic nature of spectatorship and empathy. In an interview with Marq Smith, W.J.T. Mitchell speculated that “the most interesting new questions for visual studies . . . will be located at the frontiers of visuality, the places where seeing approaches a limit” (36). I would suggest that medical images are one such frontier: an ethical borderland in which legal definitions of privacy, personhood and human rights compete with the contemporary politics of witnessing, memory and memorialisation; a space of fantasy where fascination and aversion are found in equal measure. The photograph in question (Figure 3) is a pre-operative record of one of Gillies’ patients, who was also draw.

Res derived from global flow networks are a proxy of socioeconomic

Res derived from global flow networks are a proxy of socioeconomic activities and therefore highly correlated with the explored indicators. It is an open question as to whether a highly central position in the network leads to favourable socio-economic outcomes or vica-versa. The structural connectedness of a country in the global network represents the number of opportunities a country has to exchange goods, information and resources with our countries–the more opportunities, the higher the exchange and therefore socioeconomic benefit. An analogous relation between the social network of an individual and that individual’s poverty score supports this hypothesis [14]. A broad longitudinal study would be necessary to assert whether a country’s growth in connections precedes its economic growth or vice versa which is beyond the scope of this work. Next, we will look at the community structure of countries across networks and evaluate their community multiplexity to show that countries with similar socioeconomic profiles tend to cluster together, much like in social networks.Global Community AnalysisIn the previous section we related network measures to various socioeconomic indicators, showing that metrics such as the network Anlotinib web degree can be used to estimate wellbeing at a national level. In this section, we further examine the connectedness between pairs of countries through community structure across network layers as a form of socioeconomic similarity. We use the Louvain modularity optimisation method [40] for community detection in each individual network,PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,14 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 8. Country community membership for each network. doi:10.1371/journal.pone.0155976.gwhich takes into account the tie strength of relationships between countries and finds the optimal split in terms of disconnectedness in the international network. This returns between 4? communities for each network, the geographical distribution of which is shown in Fig 8. Although communities naturally seem to be very driven by geography in physical flow networks, this is not the case in digital networks where communities are geographically dispersed. This is an indication of the difference in the way countries connect through post, trade, migration and flights rather than on the IP and social media networks. However, what does it mean for two countries to be both members of the same network community? Common community membership indicates a level of connectedness between two countries, which is beyond the randomly expected for the network. It is often observed that nodes in the same communities share many similar properties, therefore it can be expected that pairs of nodes which share multiple communities across networks are even more similar. In this work, we measure the overlap in pairwise membership between pairs of countries across our six networks as the community multiplexity index, a measure of socioeconomic similarity. Our hypothesis is that countries that are paired together in communities across more networks are more likely to be socioeconomically similar. We measure SNDX-275 web similarity here as the absolute difference between each indicator from the previous section for two countries and plot that against their community multiplexity. For example, the United States has an average life expectancy of 70 years, whereas Afghanistan has an average life expe.Res derived from global flow networks are a proxy of socioeconomic activities and therefore highly correlated with the explored indicators. It is an open question as to whether a highly central position in the network leads to favourable socio-economic outcomes or vica-versa. The structural connectedness of a country in the global network represents the number of opportunities a country has to exchange goods, information and resources with our countries–the more opportunities, the higher the exchange and therefore socioeconomic benefit. An analogous relation between the social network of an individual and that individual’s poverty score supports this hypothesis [14]. A broad longitudinal study would be necessary to assert whether a country’s growth in connections precedes its economic growth or vice versa which is beyond the scope of this work. Next, we will look at the community structure of countries across networks and evaluate their community multiplexity to show that countries with similar socioeconomic profiles tend to cluster together, much like in social networks.Global Community AnalysisIn the previous section we related network measures to various socioeconomic indicators, showing that metrics such as the network degree can be used to estimate wellbeing at a national level. In this section, we further examine the connectedness between pairs of countries through community structure across network layers as a form of socioeconomic similarity. We use the Louvain modularity optimisation method [40] for community detection in each individual network,PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,14 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 8. Country community membership for each network. doi:10.1371/journal.pone.0155976.gwhich takes into account the tie strength of relationships between countries and finds the optimal split in terms of disconnectedness in the international network. This returns between 4? communities for each network, the geographical distribution of which is shown in Fig 8. Although communities naturally seem to be very driven by geography in physical flow networks, this is not the case in digital networks where communities are geographically dispersed. This is an indication of the difference in the way countries connect through post, trade, migration and flights rather than on the IP and social media networks. However, what does it mean for two countries to be both members of the same network community? Common community membership indicates a level of connectedness between two countries, which is beyond the randomly expected for the network. It is often observed that nodes in the same communities share many similar properties, therefore it can be expected that pairs of nodes which share multiple communities across networks are even more similar. In this work, we measure the overlap in pairwise membership between pairs of countries across our six networks as the community multiplexity index, a measure of socioeconomic similarity. Our hypothesis is that countries that are paired together in communities across more networks are more likely to be socioeconomically similar. We measure similarity here as the absolute difference between each indicator from the previous section for two countries and plot that against their community multiplexity. For example, the United States has an average life expectancy of 70 years, whereas Afghanistan has an average life expe.

N scan or take a photo of the object in their

N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Saroglitazar MagnesiumMedChemExpress Saroglitazar Magnesium competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the Pedalitin permethyl ether dose application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known to be related to BMI (Table 3). Some covariates such as unemployment and smoking have been shown in the PX105684MedChemExpress Belinostat literature to be negatively associated with BMI, e.g. on average, smokers have a lower BMI [11]. In our study such Basmisanil cost Characteristics were more common among maltreated groups: e.g., prevalence of smoking and unemployment 23y to 50y was higher in the maltreated than nonmaltreated (Table 3). Potentially, these differences would lower the adult BMI among those exposed to childhood maltreatment. Allowance for such factors and their changes over time, as well as other covariates, is important for understanding associations with BMI at specific ages and BMI trajectories. Modelled lifetime trajectories of zBMI and obesity risk (Table 4 and S2 Table) confirmed the patterns with age suggested by simple analyses.Childhood abuseIn both genders there was a positive linear association between zBMI gain with age and physical abuse, by 0.006/y (males) and 0.007/y (females) after adjustment for all covariatesPLOS ONE | DOI:10.1371/journal.pone.0119985 March 26,7 /Child Maltreatment and BMI TrajectoriesTable 3. Characteristics of those with no childhood maltreatment and those abused or neglected ( ). Abuse Non-maltreated Males

‘ coordinate is the percentage of roles (s)he accepted for each

‘ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) BLU-554 site extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role ��-Amanitin chemical information acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.’ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of SB 202190 molecular weight importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though A-836339 site Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the PD150606 site treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective order PD150606 interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

His flexibility in order to achieve certain caregiving ends. Yet this

His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author CBIC2 supplier Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child BMS-214662MedChemExpress BMS-214662 Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.

N a specific form.MethodsThe ORION statement for transparent reporting of

N a specific form.MethodsThe ORION statement for transparent reporting of intervention studies concerning healthcare-acquired infections was followed [36].SettingDelfos Medical Center is a private 200-bed hospital with teaching nursing activity, with about 12,000 admissions and 50,000 patient-days each year. Almost 90 of the rooms are single. There are eight medical-surgical wards and a polyvalent intensive care unit (ICU) with 11 beds attending nearly 500 patients each year. A Nosocomial Infection Control Unit (NICU) was created in 2002 as part of the Infection Committee, which is formed by a full-time specialist in epidemiology and infectious diseases and by an infection control nurse.Outcomes variablesThe primary outcome was HH compliance calculated by dividing the number of HH episodes by the number of potential opportunities. The data was stratified by type of indications, working areas and professional category. Our retrospective control data included three sessions of HH audits performed over a week in October 2007, January 2008 and April 2008.These audits were performed following a similar procedure as that used during the intervention period (with the exception that the moment “after touching surroundings” was not evaluated) and were conducted also by nosocomial infection control and nursing supervisors’ staff.Study DesignWe developed a “pre-post intervention” study through statistical comparison of HH performance at baseline and the two intervention phases. Furthermore, we performed prospective time series analysis through statistical process control (SPC) on HH during phase 2, alcohol hand rub solution (AHRs) consumption, and rate of healthcare-acquired MRSA colonization or infection (as detected by means of clinical Pepstatin manufacturer samples only).The Ethics Committee from Delfos Medical Center approved conduct ofPLOS ONE | www.plosone.orgHospital Wide Hand Hygiene InterventionTable 1. Main characteristics of a 2 phase multifaceted hospital-wide hand hygiene intervention, Delfos Medical Center (2010?2011).Periods and data Preintervention period (March 2007 ecember 2009)Description Promotion of hand hygiene (HH) was performed but it was neither structured nor sustained on time. A limited HH campaign based on staff education, reminders (March 2007 ctober 2007) followed by limited six-month HH audit by direct observations (October 2007?April 2008) over a week (basal, and on month 3 and 6) was conducted. The alcohol hand rub solution (AHRs) was changed on June 2008 (SterilliumH gel, Bode Chemie, Hamburg, Germany); at this point, AHRs dispensers were located outside each room (corridor) and in the nursing carts. Isolation practices and HH promotion was reinforced during pandemic H1N1 threat (June2009-September 2009). Phase 2 (January 2011 ecember 2011) Continuous Quality Improvement (CQI) Promotion locally developed by Infection Control Unit and Supervisor’s Nursing Department. AHRs were placed at all patient beds in conventional wards while maintaining those at corridors. At this point the ratio AHRs dispensers/bed was 1.56 (340/217).Hospital Wide Intervention Phase 1 (January 2010 ecember 2010) Epidemiological context Catalonian Regional Campaign promoted by the “Alliance for Patient Safety” supported by WHO educational resources. AHRs were placed at all bedsides on high risk areas (PNPP site Emergency Department and Intensive Care Unit). At this point the ratio AHRs dispensers/bed was 0.57 (123/217).1, Promotion of easy access to hand-rub solution.N a specific form.MethodsThe ORION statement for transparent reporting of intervention studies concerning healthcare-acquired infections was followed [36].SettingDelfos Medical Center is a private 200-bed hospital with teaching nursing activity, with about 12,000 admissions and 50,000 patient-days each year. Almost 90 of the rooms are single. There are eight medical-surgical wards and a polyvalent intensive care unit (ICU) with 11 beds attending nearly 500 patients each year. A Nosocomial Infection Control Unit (NICU) was created in 2002 as part of the Infection Committee, which is formed by a full-time specialist in epidemiology and infectious diseases and by an infection control nurse.Outcomes variablesThe primary outcome was HH compliance calculated by dividing the number of HH episodes by the number of potential opportunities. The data was stratified by type of indications, working areas and professional category. Our retrospective control data included three sessions of HH audits performed over a week in October 2007, January 2008 and April 2008.These audits were performed following a similar procedure as that used during the intervention period (with the exception that the moment “after touching surroundings” was not evaluated) and were conducted also by nosocomial infection control and nursing supervisors’ staff.Study DesignWe developed a “pre-post intervention” study through statistical comparison of HH performance at baseline and the two intervention phases. Furthermore, we performed prospective time series analysis through statistical process control (SPC) on HH during phase 2, alcohol hand rub solution (AHRs) consumption, and rate of healthcare-acquired MRSA colonization or infection (as detected by means of clinical samples only).The Ethics Committee from Delfos Medical Center approved conduct ofPLOS ONE | www.plosone.orgHospital Wide Hand Hygiene InterventionTable 1. Main characteristics of a 2 phase multifaceted hospital-wide hand hygiene intervention, Delfos Medical Center (2010?2011).Periods and data Preintervention period (March 2007 ecember 2009)Description Promotion of hand hygiene (HH) was performed but it was neither structured nor sustained on time. A limited HH campaign based on staff education, reminders (March 2007 ctober 2007) followed by limited six-month HH audit by direct observations (October 2007?April 2008) over a week (basal, and on month 3 and 6) was conducted. The alcohol hand rub solution (AHRs) was changed on June 2008 (SterilliumH gel, Bode Chemie, Hamburg, Germany); at this point, AHRs dispensers were located outside each room (corridor) and in the nursing carts. Isolation practices and HH promotion was reinforced during pandemic H1N1 threat (June2009-September 2009). Phase 2 (January 2011 ecember 2011) Continuous Quality Improvement (CQI) Promotion locally developed by Infection Control Unit and Supervisor’s Nursing Department. AHRs were placed at all patient beds in conventional wards while maintaining those at corridors. At this point the ratio AHRs dispensers/bed was 1.56 (340/217).Hospital Wide Intervention Phase 1 (January 2010 ecember 2010) Epidemiological context Catalonian Regional Campaign promoted by the “Alliance for Patient Safety” supported by WHO educational resources. AHRs were placed at all bedsides on high risk areas (Emergency Department and Intensive Care Unit). At this point the ratio AHRs dispensers/bed was 0.57 (123/217).1, Promotion of easy access to hand-rub solution.

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological Z-DEVD-FMK biological activity energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid T0901317 web ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.

N scan or take a photo of the object in their

N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level AZD0865MedChemExpress Linaprazan expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been buy Mikamycin IA recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.

Y parts ] Cancer ] Keloid ] Death ] others, (please specify). . .Surgery Research and

Y parts ] Cancer ] Keloid ] Death ] others, (please specify). . .Surgery Research and Practice (23) If (22) is yes, which of the following do you think it is due to? [ ] Lack of facilities/equipment [ ] Lack of Modern operative techniques [ ] Lack of adequate pre/peri/post-operative care [ ] Inexperienced personnel [ ] Others (specify). . . (24) Do you think the outcome of cosmetic surgeries done in Nigeria and outside the country differ? [ ] Yes [ ] No [ ] Not sure (25) Would you advice any close relative of yours to do cosmetic surgery when he/she needs one? [ ] Yes [ ] No [ ] Not sure (26) Do you think Cosmetic Surgeries are necessary at all? [ ] Yes [ ] No [ ] Not sure (27) If yes, which one(s) of these do you think is/are necessary? [ [ [ [ [ [ [ [ [ ] Breast Augmentation ] Breast Reduction ] Mastopexy ] Rhinoplasty ] Face lift ] Blepharoplasty ] Liposuction ] Abdominoplasty ] Cleft Surgery(17) Do you think the risk of cosmetic procedure is greater than other surgical procedures? [ ] Yes [ ] No [ ] Not sure (18) Are you aware of any facilities where Cosmetic Surgery is done in your locality? [ ] Yes [ ] No [ ] Not sure (19) If (18) is yes, mention the facilities you know. . . (20) You would like to rate the facilities for Cosmetic Surgery in Nigeria as? [ [ [ [ ] Excellent ] Good ] Average ] BadSection 3: Attitude and Disposition to Cosmetic Surgery (21) If you were to make a choice, will you chose Nigerian facilities over facilities abroad for cosmetic surgery? [ ] Yes [ ] No [ ] Not sure (22) Do you think the complications associated with cosmetic surgeries done in Nigeria differ from the ones done outside the country? [ ] Yes [ ] No [ ] Not sure(28) If cosmetic surgeries were done free, would you go for any Cosmetic surgery of your choice? [ ] Yes [ ] No [ ] Not sure (29) Do you think it is godly to go for cosmetic surgery? [ ] Yes [ ] No [ ] Not sureSurgery Research and Practice (30) Do you think people’s disposition will change about you if you go for cosmetic surgery? [ ] Yes [ ] No [ ] Not sure (31) If you were aware that someone did cosmetic surgery, will it negatively affect your relationship with such a person? [ ] Yes [ ] No [ ] Not sure (32) Would you be open with the information that you have done Cosmetic Surgery before if you did one? [ ] Yes [ ] No [ ] Not sure (33) Do you consider Cosmetic Surgery as socially acceptable in Nigeria? [ ] Yes [ ] No [ ] Not sure (34) If (33) is yes, to what extent do you think it is acceptable? [ ] Widely acceptable [ ] Averagely acceptable [ ] Not acceptable (35) If (33) is no, which of the following do you think affects the acceptability of cosmetic surgeries? [ [ [ [ [ [ ] Societal taboos ] Awareness ] Knowledge ] Exposure ] Environment ] Others, (Z)-4-Hydroxytamoxifen site specify. . . [ ] Low socioeconomic Class [ ] Middle Class [ ] Lower Middle [ ] Upper Middle [ ] High Class Level of Education [ ] Literate [ ] Illiterate(38) Do you know of any taboo that is against cosmetic surgeries? [ ] Yes [ ] No [ ] Not sure (39) If (38) is yes, specify. . . (40) Would you like that more awareness program on cosmetic surgery be done? [ ] Yes [ ] No [ ] Not sure (41) On what platform will you recommend the awareness to be done? Please specify. . . Signature/Thumbprint: . . . Date: . . .MS023 supplier conflict of InterestsThe authors declare that there is no conflict of interests regarding the publication of this paper.
The use of expressive art forms,1 such as dance, photo-essays and theatre, for the research enterprise has been advoc.Y parts ] Cancer ] Keloid ] Death ] others, (please specify). . .Surgery Research and Practice (23) If (22) is yes, which of the following do you think it is due to? [ ] Lack of facilities/equipment [ ] Lack of Modern operative techniques [ ] Lack of adequate pre/peri/post-operative care [ ] Inexperienced personnel [ ] Others (specify). . . (24) Do you think the outcome of cosmetic surgeries done in Nigeria and outside the country differ? [ ] Yes [ ] No [ ] Not sure (25) Would you advice any close relative of yours to do cosmetic surgery when he/she needs one? [ ] Yes [ ] No [ ] Not sure (26) Do you think Cosmetic Surgeries are necessary at all? [ ] Yes [ ] No [ ] Not sure (27) If yes, which one(s) of these do you think is/are necessary? [ [ [ [ [ [ [ [ [ ] Breast Augmentation ] Breast Reduction ] Mastopexy ] Rhinoplasty ] Face lift ] Blepharoplasty ] Liposuction ] Abdominoplasty ] Cleft Surgery(17) Do you think the risk of cosmetic procedure is greater than other surgical procedures? [ ] Yes [ ] No [ ] Not sure (18) Are you aware of any facilities where Cosmetic Surgery is done in your locality? [ ] Yes [ ] No [ ] Not sure (19) If (18) is yes, mention the facilities you know. . . (20) You would like to rate the facilities for Cosmetic Surgery in Nigeria as? [ [ [ [ ] Excellent ] Good ] Average ] BadSection 3: Attitude and Disposition to Cosmetic Surgery (21) If you were to make a choice, will you chose Nigerian facilities over facilities abroad for cosmetic surgery? [ ] Yes [ ] No [ ] Not sure (22) Do you think the complications associated with cosmetic surgeries done in Nigeria differ from the ones done outside the country? [ ] Yes [ ] No [ ] Not sure(28) If cosmetic surgeries were done free, would you go for any Cosmetic surgery of your choice? [ ] Yes [ ] No [ ] Not sure (29) Do you think it is godly to go for cosmetic surgery? [ ] Yes [ ] No [ ] Not sureSurgery Research and Practice (30) Do you think people’s disposition will change about you if you go for cosmetic surgery? [ ] Yes [ ] No [ ] Not sure (31) If you were aware that someone did cosmetic surgery, will it negatively affect your relationship with such a person? [ ] Yes [ ] No [ ] Not sure (32) Would you be open with the information that you have done Cosmetic Surgery before if you did one? [ ] Yes [ ] No [ ] Not sure (33) Do you consider Cosmetic Surgery as socially acceptable in Nigeria? [ ] Yes [ ] No [ ] Not sure (34) If (33) is yes, to what extent do you think it is acceptable? [ ] Widely acceptable [ ] Averagely acceptable [ ] Not acceptable (35) If (33) is no, which of the following do you think affects the acceptability of cosmetic surgeries? [ [ [ [ [ [ ] Societal taboos ] Awareness ] Knowledge ] Exposure ] Environment ] Others, specify. . . [ ] Low socioeconomic Class [ ] Middle Class [ ] Lower Middle [ ] Upper Middle [ ] High Class Level of Education [ ] Literate [ ] Illiterate(38) Do you know of any taboo that is against cosmetic surgeries? [ ] Yes [ ] No [ ] Not sure (39) If (38) is yes, specify. . . (40) Would you like that more awareness program on cosmetic surgery be done? [ ] Yes [ ] No [ ] Not sure (41) On what platform will you recommend the awareness to be done? Please specify. . . Signature/Thumbprint: . . . Date: . . .Conflict of InterestsThe authors declare that there is no conflict of interests regarding the publication of this paper.
The use of expressive art forms,1 such as dance, photo-essays and theatre, for the research enterprise has been advoc.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering PF-04418948 molecular weight Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, AZD4547 biological activity perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

T the funeral … they said that I should take the child.

T the funeral … they said that I should take the child. And I said, how will I take the child yet I’m sick? And the thieves have taken all my animals. And at least there, he will have milk to eat, and I refused to take him … this child is yours not mine. And after I buried the mother, three days passed … they came and brought this baby saying their mother said this child is supposed to be here …Yet I said I don’t need him. And they left him. He was very sick. He was very sick. He nearly died … ‘M’e Masello highlights the complexity of fostering AIDS Shikonin clinical trials orphans. She felt that she did not have the resources or physical capabilities to care for Lebo and his siblings, yet there was no one else willing to care for them. The children were left with her after lengthy discussions between the two families and their chiefs. However, this does not indicate any lack of love or affection for the children on her part. She was particularly close with Lebo. She often emphasized how happy she was to be living with the children, and how much they helped her. Nevertheless, although she was deemed most capable of caring for Lebo and his siblings, this did not mean that they were ensured adequate care. Although, initially, ‘M’e Masello was physically and mentally able to provide for the children, for the last year of her life she was unable to give them the care they needed. This was especially true for Lebo, whose HIV regimen was particularly complex owing to numerous misdiagnoses. As a result of his grandmother’s sickness, his adherence to his antiretroviral treatment declined. I learned recently that ‘M’e Masello had died. Now the struggle to find a caregiver for the children has begun again.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptConclusionA history of dependence on migrant labour, changing marriage practices, and HIV/ AIDS have altered kin-based fostering networks among Basotho families. More children are in need of care, yet there are fewer caregivers to provide it. In rural communities, whereJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageinstitutionalized care is unavailable and external support is limited, kin-based care is the only option. In order to cope with these pressures, families are organizing themselves by focusing their resources matrilocally. Yet they are making sense of this model of care within the patrilineal system of child fostering. This is most evident in the ways family members negotiate for the care of children. In particular, primarily elderly female caregivers attempt to demonstrate their right to the children, often focusing on the presence or absence of bridewealth as key to their negotiation strategies. Simultaneously, there is an overriding emphasis on the quality of care that potential caregivers can provide (Ksoll 2007). The day-to-day role of women in this system has not drastically changed: women still do the majority of the care work. In fact, women are being called upon to care for an increased number of children — including those with greater health problems — yet with diminishing resources. What has changed, however, is the role a Vasoactive Intestinal Peptide (human, rat, mouse, rabbit, canine, porcine) web woman’s natal family plays in supporting her. In a context where marriage is a risk factor for contracting HIV (Smith 2007), but where having children still holds significant social value (Booth 2004), an easily dissolvable marriage may be seen as advantageous by mothers and maternal grandmothers, who can manipulate t.T the funeral … they said that I should take the child. And I said, how will I take the child yet I’m sick? And the thieves have taken all my animals. And at least there, he will have milk to eat, and I refused to take him … this child is yours not mine. And after I buried the mother, three days passed … they came and brought this baby saying their mother said this child is supposed to be here …Yet I said I don’t need him. And they left him. He was very sick. He was very sick. He nearly died … ‘M’e Masello highlights the complexity of fostering AIDS orphans. She felt that she did not have the resources or physical capabilities to care for Lebo and his siblings, yet there was no one else willing to care for them. The children were left with her after lengthy discussions between the two families and their chiefs. However, this does not indicate any lack of love or affection for the children on her part. She was particularly close with Lebo. She often emphasized how happy she was to be living with the children, and how much they helped her. Nevertheless, although she was deemed most capable of caring for Lebo and his siblings, this did not mean that they were ensured adequate care. Although, initially, ‘M’e Masello was physically and mentally able to provide for the children, for the last year of her life she was unable to give them the care they needed. This was especially true for Lebo, whose HIV regimen was particularly complex owing to numerous misdiagnoses. As a result of his grandmother’s sickness, his adherence to his antiretroviral treatment declined. I learned recently that ‘M’e Masello had died. Now the struggle to find a caregiver for the children has begun again.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptConclusionA history of dependence on migrant labour, changing marriage practices, and HIV/ AIDS have altered kin-based fostering networks among Basotho families. More children are in need of care, yet there are fewer caregivers to provide it. In rural communities, whereJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageinstitutionalized care is unavailable and external support is limited, kin-based care is the only option. In order to cope with these pressures, families are organizing themselves by focusing their resources matrilocally. Yet they are making sense of this model of care within the patrilineal system of child fostering. This is most evident in the ways family members negotiate for the care of children. In particular, primarily elderly female caregivers attempt to demonstrate their right to the children, often focusing on the presence or absence of bridewealth as key to their negotiation strategies. Simultaneously, there is an overriding emphasis on the quality of care that potential caregivers can provide (Ksoll 2007). The day-to-day role of women in this system has not drastically changed: women still do the majority of the care work. In fact, women are being called upon to care for an increased number of children — including those with greater health problems — yet with diminishing resources. What has changed, however, is the role a woman’s natal family plays in supporting her. In a context where marriage is a risk factor for contracting HIV (Smith 2007), but where having children still holds significant social value (Booth 2004), an easily dissolvable marriage may be seen as advantageous by mothers and maternal grandmothers, who can manipulate t.

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher order purchase GS-5816 Duvoglustat explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.

Of internal edges (mentions between users), — the number of internal

Of internal edges (mentions between users), — the number of internal edges (mentions) per node (this gives a measure of how much activity there is inside the community), — the conductance and the weighted conductance of the NS-018 web community within the whole network, — the mean sentiment of edges within the community, using the (MC) measure,6 — whether the community consisted of a single connected component (good candidate communities will of course be connected; however, very infrequently the Louvain method can generate disconnected communities, by removing a `bridge’ node during its iterative refinement of its communities), — the fraction of internal mentions with non-zero sentiment (some of our candidate communities were composed mainly of users speaking a non-English language, and we used this measure to filter them out; tweets in other languages are likely to be assigned a zero sentiment score, because the sentiment scoring algorithm does not find any English words with which to gauge the sentiment),4rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………This code is freely available from https://sites.google.com/site/findcommunities/.This algorithm, and some refinements to it, are also implemented in the CFINDER program, freely available from http://www. cfinder.org/.6 Owing to time constraints and the large number of tweets involved in community detection, we decided not to calculate the (SS) and (L) scores at this stage.– some statistics summarizing the role played in the community by recently registered users; and — a breakdown of the frequency of participation of users in the community. (For each user in the community, we counted how many distinct days they had been active on Twitter in our data, and then calculated the percentage of these days on which they had posted within the candidate community. We calculated the average across all users in the community, and also split the users up into five bins.) Based on the above statistics, we short-listed a subset of communities and performed a manual inspection of a sample of the tweets within the community, to assess the topics talked about and a visualization of the community, using the program VISONE (http://visone.info/html/about.html) for this subset. In the end, we selected 18 communities to monitor and study. Table 1 shows most of the statistics listed above for these 18 communities, in size order. In each numerical column, the get RRx-001 highest six values are highlighted in italics and the lowest six values are highlighted in bold (recall that for conductance and weighted conductance, lower values indicate a more tightly knit community). The `Algorithm’ column contains `L’ for the Louvain method, `W’ for the weighted Louvain method and `K’ for the k-cliquecommunities method. We chose six communities from each algorithm. Table 2 shows frequency of participation, with communities ranked by the third column, which gives the average user participation. This is expressed as a percentage: the percentage of days on which the user was active on Twitter (in our dataset) that they were active in the community. The rightmost five columns show, for each community, how the users’ participation levels break down into five bins. Bins with disproportionately many users in them (i.e. with values more than 0.2) are highlighted in italics. We can see that with the exception of community 4 (weddings), every community has at least a 20 `hard core’ of users, w.Of internal edges (mentions between users), — the number of internal edges (mentions) per node (this gives a measure of how much activity there is inside the community), — the conductance and the weighted conductance of the community within the whole network, — the mean sentiment of edges within the community, using the (MC) measure,6 — whether the community consisted of a single connected component (good candidate communities will of course be connected; however, very infrequently the Louvain method can generate disconnected communities, by removing a `bridge’ node during its iterative refinement of its communities), — the fraction of internal mentions with non-zero sentiment (some of our candidate communities were composed mainly of users speaking a non-English language, and we used this measure to filter them out; tweets in other languages are likely to be assigned a zero sentiment score, because the sentiment scoring algorithm does not find any English words with which to gauge the sentiment),4rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………This code is freely available from https://sites.google.com/site/findcommunities/.This algorithm, and some refinements to it, are also implemented in the CFINDER program, freely available from http://www. cfinder.org/.6 Owing to time constraints and the large number of tweets involved in community detection, we decided not to calculate the (SS) and (L) scores at this stage.– some statistics summarizing the role played in the community by recently registered users; and — a breakdown of the frequency of participation of users in the community. (For each user in the community, we counted how many distinct days they had been active on Twitter in our data, and then calculated the percentage of these days on which they had posted within the candidate community. We calculated the average across all users in the community, and also split the users up into five bins.) Based on the above statistics, we short-listed a subset of communities and performed a manual inspection of a sample of the tweets within the community, to assess the topics talked about and a visualization of the community, using the program VISONE (http://visone.info/html/about.html) for this subset. In the end, we selected 18 communities to monitor and study. Table 1 shows most of the statistics listed above for these 18 communities, in size order. In each numerical column, the highest six values are highlighted in italics and the lowest six values are highlighted in bold (recall that for conductance and weighted conductance, lower values indicate a more tightly knit community). The `Algorithm’ column contains `L’ for the Louvain method, `W’ for the weighted Louvain method and `K’ for the k-cliquecommunities method. We chose six communities from each algorithm. Table 2 shows frequency of participation, with communities ranked by the third column, which gives the average user participation. This is expressed as a percentage: the percentage of days on which the user was active on Twitter (in our dataset) that they were active in the community. The rightmost five columns show, for each community, how the users’ participation levels break down into five bins. Bins with disproportionately many users in them (i.e. with values more than 0.2) are highlighted in italics. We can see that with the exception of community 4 (weddings), every community has at least a 20 `hard core’ of users, w.

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease RR6 site states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution Sitravatinib web kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.

Ctancy of 50, the absolute difference between the two is 20 which represents

Ctancy of 50, the absolute difference between the two is 20 which represents low similarity when compared to the United Kingdom’s life expectancy of 72 for this indicator. In Fig 9, we can AM152 site observe the variations in similarity for countries with different levels of community multiplexity. What is immediately striking is that countries that share a maximal number of communities and therefore exhibit the greatest community multiplexity, have the smallest margin of difference across all indicators. This suggests that countries with the highest community multiplexity have a very similar socioeconomic profile. This is confirmed by a two-sample Kolmogorov-Smirnov test between the distributions of differences in each indicator for pairs sharing different numbers of communities. Tenapanor site Although the KS statistic is lower between groups sharing 0 and 1 communities (apx. 0.1 for all indicators and p-value <0.01), it is very high for groups between 1 and 6 communities (0.4 and above, p-value <0.01), except for mobile phone penetration (detailed KS test results are presented in S1 Table).PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,15 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 9. Socioeconomic difference margin between countries who share communities in the global flow networks. doi:10.1371/journal.pone.0155976.gFurther to this observation, in most indicators there is a very strong significance in the level of community multiplexity--the higher the community multiplexity index between two countries, the smaller the difference between their socioeconomic profiles. There are notable exceptions to this such as the mobile phone penetration ratio, where it appears that beyond the highest level of multiplexity, all other countries are relatively similar in this aspect with low variation even for those pairs of countries which share no communities. For all other indicators such as GDP, Literacy ratio, HDI and Internet penetration, there is a dramatic increase in similarity past a community multiplexity of 3. Ultimately, these similarities can be used to estimate the wellbeing of countries for which it is unknown but can be estimated from its neighbours.DiscussionBig data is often related to real-time data captured through the Internet or social networks. However, the digital divide makes access to big data insights for development more challenging in the least developed and many developing and emerging countries. Can we rely on other networks to overcome these critical data gaps in view of better measuring and monitoring developmental progress? This is particularly important following the United Nations adoption of the Sustainable Development Goals (SDG) in September 2015, made of 17 goals, 169 targets and almost 200 universal indicators, each of them calling for regular and increasingly disaggregated monitoring in every country during the 2016?0 period. This commitment invites a nuanced discussion on the nature and importance of measurement, inference and triangulation of data sources. This discussion is particularly prescient in the face of complex intertwined developmental challenges in an age of increased globalisation, economic interdependence and climate change. The work presented above has clearly shown the value of measuring, comparing, and combining metrics of global connectivity across six different global networks in order to approximate socioeconomic indicators and to identify network communities.Ctancy of 50, the absolute difference between the two is 20 which represents low similarity when compared to the United Kingdom's life expectancy of 72 for this indicator. In Fig 9, we can observe the variations in similarity for countries with different levels of community multiplexity. What is immediately striking is that countries that share a maximal number of communities and therefore exhibit the greatest community multiplexity, have the smallest margin of difference across all indicators. This suggests that countries with the highest community multiplexity have a very similar socioeconomic profile. This is confirmed by a two-sample Kolmogorov-Smirnov test between the distributions of differences in each indicator for pairs sharing different numbers of communities. Although the KS statistic is lower between groups sharing 0 and 1 communities (apx. 0.1 for all indicators and p-value <0.01), it is very high for groups between 1 and 6 communities (0.4 and above, p-value <0.01), except for mobile phone penetration (detailed KS test results are presented in S1 Table).PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,15 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 9. Socioeconomic difference margin between countries who share communities in the global flow networks. doi:10.1371/journal.pone.0155976.gFurther to this observation, in most indicators there is a very strong significance in the level of community multiplexity--the higher the community multiplexity index between two countries, the smaller the difference between their socioeconomic profiles. There are notable exceptions to this such as the mobile phone penetration ratio, where it appears that beyond the highest level of multiplexity, all other countries are relatively similar in this aspect with low variation even for those pairs of countries which share no communities. For all other indicators such as GDP, Literacy ratio, HDI and Internet penetration, there is a dramatic increase in similarity past a community multiplexity of 3. Ultimately, these similarities can be used to estimate the wellbeing of countries for which it is unknown but can be estimated from its neighbours.DiscussionBig data is often related to real-time data captured through the Internet or social networks. However, the digital divide makes access to big data insights for development more challenging in the least developed and many developing and emerging countries. Can we rely on other networks to overcome these critical data gaps in view of better measuring and monitoring developmental progress? This is particularly important following the United Nations adoption of the Sustainable Development Goals (SDG) in September 2015, made of 17 goals, 169 targets and almost 200 universal indicators, each of them calling for regular and increasingly disaggregated monitoring in every country during the 2016?0 period. This commitment invites a nuanced discussion on the nature and importance of measurement, inference and triangulation of data sources. This discussion is particularly prescient in the face of complex intertwined developmental challenges in an age of increased globalisation, economic interdependence and climate change. The work presented above has clearly shown the value of measuring, comparing, and combining metrics of global connectivity across six different global networks in order to approximate socioeconomic indicators and to identify network communities.

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known to be related to BMI (Table 3). Some covariates such as unemployment and smoking have been shown in the literature to be negatively associated with BMI, e.g. on average, smokers have a lower BMI [11]. In our study such characteristics were more common among TSA chemical information maltreated groups: e.g., prevalence of smoking and unemployment 23y to 50y was ZM241385 manufacturer higher in the maltreated than nonmaltreated (Table 3). Potentially, these differences would lower the adult BMI among those exposed to childhood maltreatment. Allowance for such factors and their changes over time, as well as other covariates, is important for understanding associations with BMI at specific ages and BMI trajectories. Modelled lifetime trajectories of zBMI and obesity risk (Table 4 and S2 Table) confirmed the patterns with age suggested by simple analyses.Childhood abuseIn both genders there was a positive linear association between zBMI gain with age and physical abuse, by 0.006/y (males) and 0.007/y (females) after adjustment for all covariatesPLOS ONE | DOI:10.1371/journal.pone.0119985 March 26,7 /Child Maltreatment and BMI TrajectoriesTable 3. Characteristics of those with no childhood maltreatment and those abused or neglected ( ). Abuse Non-maltreated Males

N scan or take a photo of the object in their

N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence Serabelisib site according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the GLPG0187 side effects global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.

Scores.21 This was not observed. In fact, the absence of reaction

Scores.21 This was not observed. In fact, the purchase Pleconaril absence of reaction time differences has been previously observed in a study looking at schizotypy and the N400 potential.22 Thus, the participants who accepted more extraordinary roles did not do it because they were less cognizant of their inappropriateness. Their strategy was similar to that of other participants: all subjects were quicker at accepting ordinary or favorable roles than they were at accepting extraordinary or unfavorable roles (Figure 3). Future studies should ask the participants to rate the strength of their will to accept each role as this rating might permit to explain more disorganization and schizotypy variance than the acceptance percentages and the reaction times collected here. These studies should also openly ask participants which roles, even extraordinary ones, they would have likely considered. These roles would enrich the list and their strength ratings may further increase the individual fit. Furthermore, the paradigm could be tried in other patient populations suffering from mental disorders that may include disorganization and other psychotic features, such as schizophrenia, bipolar disorder, Tyrphostin AG 490 site postpartum psychosis, and schizoaffective disorder. The drive to perform extraordinary roles could exist in any of them. The drive to perform unfavorable roles should also be studied in disorders including a lack of empathy, such as antisocial diagnosis. The general follow-up of patients might be improved by taking their drives into account in the psychotherapy process. MATERIALS AND METHODS ParticipantsA set of 209 healthy volunteers was recruited through online advertisements, posted on two sites for the general population (Craigslist and Kijiji) and one site for university students: McGill classifieds. This set included two samples that underwent similar versions of the experiment (see the procedure section). The first sample encompassed 159 participants (97 women) who were between 18 and 30 years of age (M = 22.80, s.d. = 3.19) and had a number of years of education comprised between 10 and 21 (M = 14.56, s.d. = 1.89). Eight of its individuals did not disclose their education level. The other sample involved 44 individuals (25 women) between the ages of 18 and 30 (M = 22.07, s.d. = 2.77) with an education between 12 and 18 years (M = 14.79, s.d. = 1.21). All the participants were native English speakers or had acquired a minimum of 10 years of English education. They reported no previous history of neurological conditions, intellectual deficits, alcohol or drug abuse, and denied taking medication related to a psychiatric disorder during the two previous years. There were no significant demographic, clinical, and behavioral differences between the two samples. The participants were informed about the purpose of the study and signed a consent form approved by the Research Ethics Board of the Douglas Mental Health University Institute. They were debriefed following the experiment and given monetary compensation for their participation. Six subjects were excluded because they responded to less than 50 of the social roles or because they responded in more than 2,500 ms, which suggests that they were not using the same cognitive strategy as the other participants. Moreover, their acceptance percentages were more than two standard deviations above the mean, making them outliers.QuestionnairesAll the participants filled out a demographics form and the SPQ. Once prelimina.Scores.21 This was not observed. In fact, the absence of reaction time differences has been previously observed in a study looking at schizotypy and the N400 potential.22 Thus, the participants who accepted more extraordinary roles did not do it because they were less cognizant of their inappropriateness. Their strategy was similar to that of other participants: all subjects were quicker at accepting ordinary or favorable roles than they were at accepting extraordinary or unfavorable roles (Figure 3). Future studies should ask the participants to rate the strength of their will to accept each role as this rating might permit to explain more disorganization and schizotypy variance than the acceptance percentages and the reaction times collected here. These studies should also openly ask participants which roles, even extraordinary ones, they would have likely considered. These roles would enrich the list and their strength ratings may further increase the individual fit. Furthermore, the paradigm could be tried in other patient populations suffering from mental disorders that may include disorganization and other psychotic features, such as schizophrenia, bipolar disorder, postpartum psychosis, and schizoaffective disorder. The drive to perform extraordinary roles could exist in any of them. The drive to perform unfavorable roles should also be studied in disorders including a lack of empathy, such as antisocial diagnosis. The general follow-up of patients might be improved by taking their drives into account in the psychotherapy process. MATERIALS AND METHODS ParticipantsA set of 209 healthy volunteers was recruited through online advertisements, posted on two sites for the general population (Craigslist and Kijiji) and one site for university students: McGill classifieds. This set included two samples that underwent similar versions of the experiment (see the procedure section). The first sample encompassed 159 participants (97 women) who were between 18 and 30 years of age (M = 22.80, s.d. = 3.19) and had a number of years of education comprised between 10 and 21 (M = 14.56, s.d. = 1.89). Eight of its individuals did not disclose their education level. The other sample involved 44 individuals (25 women) between the ages of 18 and 30 (M = 22.07, s.d. = 2.77) with an education between 12 and 18 years (M = 14.79, s.d. = 1.21). All the participants were native English speakers or had acquired a minimum of 10 years of English education. They reported no previous history of neurological conditions, intellectual deficits, alcohol or drug abuse, and denied taking medication related to a psychiatric disorder during the two previous years. There were no significant demographic, clinical, and behavioral differences between the two samples. The participants were informed about the purpose of the study and signed a consent form approved by the Research Ethics Board of the Douglas Mental Health University Institute. They were debriefed following the experiment and given monetary compensation for their participation. Six subjects were excluded because they responded to less than 50 of the social roles or because they responded in more than 2,500 ms, which suggests that they were not using the same cognitive strategy as the other participants. Moreover, their acceptance percentages were more than two standard deviations above the mean, making them outliers.QuestionnairesAll the participants filled out a demographics form and the SPQ. Once prelimina.

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar

Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others AvasimibeMedChemExpress PD-148515 evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the ONO-4059 web superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.

Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and

Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and the case photographs of the same men housed in the Gillies Archives at Queen Mary’s Hospital in Sidcup. Tonks regarded his surgical studies as “rather dreadful subjects for the public view” (n.p.) and complained of “all the more tedious visitors” to the hospital for whom the drawings were one of the “sights” (Hone, 128). In recent years, though, the portraits have found a wider audience. They have been exhibited at the Venice Biennale, Tate Britain, the Science Museum in London, the Hunterian Museum at the Royal GSK2256098 price College of Surgeons of England, the Wellcome Collection, University College London, and the National Army Museum in Chelsea. In June 2007 the full series was made digitally available on the website of the Gillies Archives,4 and Pat Barker has spoken of them as a source of inspiration for her new novel Toby’s Room.5 The photographs of Gillies’ patients have entered the public domain alongside the drawings. A selection of complete case files from the Gillies Archives can be viewed online as part of the Wellcome-funded Sci-Art collaboration, Project Fa de, and case photographs have featured in Lonafarnib custom synthesis several recent exhibitions including Faces of Battle at the National Army Museum and War and Medicine at the Wellcome.6 Even more than the drawings, the photographs question the limits and propriety of spectatorship. At least with the pastels, one is aware — almost physically — of Tonks’ attentiveness, the qualityM E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 1 Photograph of Henry Tonks in his room at The Queen’s Hospital, Sidcup, 1917.P H OTO G R AP H I E SFIGURE 2 Horace Nicholls, Repairing War’s Ravages: Renovating facial injuries. Captain Derwent Wood painting the plate. Imperial War Museum, Q.30.457. ?IWM.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R Eof the artist’s touch and the duration of his gaze. His authority, as an artist and surgeon, licenses our own interest. The photographs appear unmediated by any aesthetic concerns: physically and psychologically naked. When I teach this material (usually to history of art students), I tend not to use the most harrowing images of facial injury and reconstructive surgery. Apart from my own discomfort, I worry how my students will respond: with pity? With disgust? Fascination? Should I name the patient, or protect his anonymity? Would he, or his relatives, want the photograph to be shown in a non-medical context? Is there a happy ending — a redemptive “after surgery” to counterbalance the “before”? These questions might give me pause for thought, but they generally remain unspoken. Here, though, I have chosen one image precisely because it confronts the interested, curious or appalled viewer with the problematic nature of spectatorship and empathy. In an interview with Marq Smith, W.J.T. Mitchell speculated that “the most interesting new questions for visual studies . . . will be located at the frontiers of visuality, the places where seeing approaches a limit” (36). I would suggest that medical images are one such frontier: an ethical borderland in which legal definitions of privacy, personhood and human rights compete with the contemporary politics of witnessing, memory and memorialisation; a space of fantasy where fascination and aversion are found in equal measure. The photograph in question (Figure 3) is a pre-operative record of one of Gillies’ patients, who was also draw.Sub-human monstrosities that bear an uncanny likeness to Tonks’ portraits and the case photographs of the same men housed in the Gillies Archives at Queen Mary’s Hospital in Sidcup. Tonks regarded his surgical studies as “rather dreadful subjects for the public view” (n.p.) and complained of “all the more tedious visitors” to the hospital for whom the drawings were one of the “sights” (Hone, 128). In recent years, though, the portraits have found a wider audience. They have been exhibited at the Venice Biennale, Tate Britain, the Science Museum in London, the Hunterian Museum at the Royal College of Surgeons of England, the Wellcome Collection, University College London, and the National Army Museum in Chelsea. In June 2007 the full series was made digitally available on the website of the Gillies Archives,4 and Pat Barker has spoken of them as a source of inspiration for her new novel Toby’s Room.5 The photographs of Gillies’ patients have entered the public domain alongside the drawings. A selection of complete case files from the Gillies Archives can be viewed online as part of the Wellcome-funded Sci-Art collaboration, Project Fa de, and case photographs have featured in several recent exhibitions including Faces of Battle at the National Army Museum and War and Medicine at the Wellcome.6 Even more than the drawings, the photographs question the limits and propriety of spectatorship. At least with the pastels, one is aware — almost physically — of Tonks’ attentiveness, the qualityM E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 1 Photograph of Henry Tonks in his room at The Queen’s Hospital, Sidcup, 1917.P H OTO G R AP H I E SFIGURE 2 Horace Nicholls, Repairing War’s Ravages: Renovating facial injuries. Captain Derwent Wood painting the plate. Imperial War Museum, Q.30.457. ?IWM.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R Eof the artist’s touch and the duration of his gaze. His authority, as an artist and surgeon, licenses our own interest. The photographs appear unmediated by any aesthetic concerns: physically and psychologically naked. When I teach this material (usually to history of art students), I tend not to use the most harrowing images of facial injury and reconstructive surgery. Apart from my own discomfort, I worry how my students will respond: with pity? With disgust? Fascination? Should I name the patient, or protect his anonymity? Would he, or his relatives, want the photograph to be shown in a non-medical context? Is there a happy ending — a redemptive “after surgery” to counterbalance the “before”? These questions might give me pause for thought, but they generally remain unspoken. Here, though, I have chosen one image precisely because it confronts the interested, curious or appalled viewer with the problematic nature of spectatorship and empathy. In an interview with Marq Smith, W.J.T. Mitchell speculated that “the most interesting new questions for visual studies . . . will be located at the frontiers of visuality, the places where seeing approaches a limit” (36). I would suggest that medical images are one such frontier: an ethical borderland in which legal definitions of privacy, personhood and human rights compete with the contemporary politics of witnessing, memory and memorialisation; a space of fantasy where fascination and aversion are found in equal measure. The photograph in question (Figure 3) is a pre-operative record of one of Gillies’ patients, who was also draw.

Cent research from the Gallup Polls indicating that Pentecostals report higher

Cent research from the Gallup Polls indicating that Pentecostals report higher levels of religious service attendance than Baptists, while Baptists, in turn, report higher levels of service attendance than Catholics and Episcopalians (Newport, 2006). The findings are also consistent with research on immigrants which found that higher service attendance among immigrants from sectarian groups (i.e., Pentecostals, Seven Day Adventists) (Alanezi Sherkat, 2008). Due to their relatively small sample sizes, many prior analyses do not differentiate Episcopalians from other religious denominations. This denominational group, however, is somewhat larger among Caribbean Blacks. The present analysis showed that despite media representations of Episcopalians as having a more secular outlook, Caribbean Blacks who are Episcopalians report levels of religiosity (i.e., non-organizational and subjective religiosity) that are comparable to persons who identify as Baptists. Several differences did emerge, however, in which both Episcopalians and Catholics engaged in other church activities less frequently than Baptists, while Catholics were less likely to be official members of their churches and to read religious materials. Foley and Hoge’s (2007) analysis of immigrant religion suggests that differences in organizational culture (e.g., house of worship, family-style, community-style, civic leader) that are broadly associated with denomination shape types of religious involvement and expression within faith communities. Catholic congregations are characterized as hierarchical and emphasizing formal structure, whereas evangelical congregations stress lay involvement and participation and cohesive social networks. Accordingly, denominational differences in participation in other church activities could be related to a greater number of internal groups and organizations (e.g., men’s and women’s choirs, auxiliary groups) within Baptist churches as compared to Catholic and Episcopalian congregations. However, it is important to exercise caution when discussing and interpreting denominational differences in religious participation, particularly in relation to statements regarding comparative levels of religious HS-173 manufacturer devotion. Normative expectations for religious involvement differ significantly by and within denominations and may be formally structured by specific practices, traditions and requirements of specific religious institutions (Foley Hoge, 2007; Newport, 2006). Immigration status was significantly related to 5 of the 10 measures of religious participation. In most instances, native born Blacks of Caribbean descent had lower levels of religious participation (i.e., church attendance, read religious AZD-8835 supplement materials, requests for prayer, and religious upbringing) than those who had immigrated. This is particularly true for immigrants who have been in the United States for 6 to 10 years and 11 to 20 years. Church membership was only exception in which very recent immigrants (0? years in U.S.) were less likely to be official members of their place of worship than native born Caribbean Blacks. This suggests that although immigrants (6 to 10 years in the U.S.) are more likely to attend church than native-born Caribbean Blacks, more recent arrivals may not have yet selected a church to join. Similarly, recent immigrants may be reluctant to officially join a church if they see their time in the U.S. as temporary. Overall, these results indicating significant relations.Cent research from the Gallup Polls indicating that Pentecostals report higher levels of religious service attendance than Baptists, while Baptists, in turn, report higher levels of service attendance than Catholics and Episcopalians (Newport, 2006). The findings are also consistent with research on immigrants which found that higher service attendance among immigrants from sectarian groups (i.e., Pentecostals, Seven Day Adventists) (Alanezi Sherkat, 2008). Due to their relatively small sample sizes, many prior analyses do not differentiate Episcopalians from other religious denominations. This denominational group, however, is somewhat larger among Caribbean Blacks. The present analysis showed that despite media representations of Episcopalians as having a more secular outlook, Caribbean Blacks who are Episcopalians report levels of religiosity (i.e., non-organizational and subjective religiosity) that are comparable to persons who identify as Baptists. Several differences did emerge, however, in which both Episcopalians and Catholics engaged in other church activities less frequently than Baptists, while Catholics were less likely to be official members of their churches and to read religious materials. Foley and Hoge’s (2007) analysis of immigrant religion suggests that differences in organizational culture (e.g., house of worship, family-style, community-style, civic leader) that are broadly associated with denomination shape types of religious involvement and expression within faith communities. Catholic congregations are characterized as hierarchical and emphasizing formal structure, whereas evangelical congregations stress lay involvement and participation and cohesive social networks. Accordingly, denominational differences in participation in other church activities could be related to a greater number of internal groups and organizations (e.g., men’s and women’s choirs, auxiliary groups) within Baptist churches as compared to Catholic and Episcopalian congregations. However, it is important to exercise caution when discussing and interpreting denominational differences in religious participation, particularly in relation to statements regarding comparative levels of religious devotion. Normative expectations for religious involvement differ significantly by and within denominations and may be formally structured by specific practices, traditions and requirements of specific religious institutions (Foley Hoge, 2007; Newport, 2006). Immigration status was significantly related to 5 of the 10 measures of religious participation. In most instances, native born Blacks of Caribbean descent had lower levels of religious participation (i.e., church attendance, read religious materials, requests for prayer, and religious upbringing) than those who had immigrated. This is particularly true for immigrants who have been in the United States for 6 to 10 years and 11 to 20 years. Church membership was only exception in which very recent immigrants (0? years in U.S.) were less likely to be official members of their place of worship than native born Caribbean Blacks. This suggests that although immigrants (6 to 10 years in the U.S.) are more likely to attend church than native-born Caribbean Blacks, more recent arrivals may not have yet selected a church to join. Similarly, recent immigrants may be reluctant to officially join a church if they see their time in the U.S. as temporary. Overall, these results indicating significant relations.

Res derived from global flow networks are a proxy of socioeconomic

Res derived from global flow networks are a proxy of socioeconomic activities and therefore highly correlated with the explored indicators. It is an open question as to whether a highly central position in the network leads to favourable socio-economic outcomes or vica-versa. The structural connectedness of a country in the global network represents the number of opportunities a country has to exchange goods, information and resources with our countries–the more opportunities, the higher the exchange and therefore socioeconomic benefit. An analogous relation between the social network of an individual and that individual’s poverty score supports this hypothesis [14]. A broad longitudinal study would be necessary to assert whether a country’s growth in connections Nutlin (3a) dose precedes its economic growth or vice versa which is beyond the scope of this work. Next, we will look at the community structure of countries across networks and evaluate their community multiplexity to show that countries with similar socioeconomic profiles tend to cluster together, much like in social networks.Global Community AnalysisIn the XL880 web previous section we related network measures to various socioeconomic indicators, showing that metrics such as the network degree can be used to estimate wellbeing at a national level. In this section, we further examine the connectedness between pairs of countries through community structure across network layers as a form of socioeconomic similarity. We use the Louvain modularity optimisation method [40] for community detection in each individual network,PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,14 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 8. Country community membership for each network. doi:10.1371/journal.pone.0155976.gwhich takes into account the tie strength of relationships between countries and finds the optimal split in terms of disconnectedness in the international network. This returns between 4? communities for each network, the geographical distribution of which is shown in Fig 8. Although communities naturally seem to be very driven by geography in physical flow networks, this is not the case in digital networks where communities are geographically dispersed. This is an indication of the difference in the way countries connect through post, trade, migration and flights rather than on the IP and social media networks. However, what does it mean for two countries to be both members of the same network community? Common community membership indicates a level of connectedness between two countries, which is beyond the randomly expected for the network. It is often observed that nodes in the same communities share many similar properties, therefore it can be expected that pairs of nodes which share multiple communities across networks are even more similar. In this work, we measure the overlap in pairwise membership between pairs of countries across our six networks as the community multiplexity index, a measure of socioeconomic similarity. Our hypothesis is that countries that are paired together in communities across more networks are more likely to be socioeconomically similar. We measure similarity here as the absolute difference between each indicator from the previous section for two countries and plot that against their community multiplexity. For example, the United States has an average life expectancy of 70 years, whereas Afghanistan has an average life expe.Res derived from global flow networks are a proxy of socioeconomic activities and therefore highly correlated with the explored indicators. It is an open question as to whether a highly central position in the network leads to favourable socio-economic outcomes or vica-versa. The structural connectedness of a country in the global network represents the number of opportunities a country has to exchange goods, information and resources with our countries–the more opportunities, the higher the exchange and therefore socioeconomic benefit. An analogous relation between the social network of an individual and that individual’s poverty score supports this hypothesis [14]. A broad longitudinal study would be necessary to assert whether a country’s growth in connections precedes its economic growth or vice versa which is beyond the scope of this work. Next, we will look at the community structure of countries across networks and evaluate their community multiplexity to show that countries with similar socioeconomic profiles tend to cluster together, much like in social networks.Global Community AnalysisIn the previous section we related network measures to various socioeconomic indicators, showing that metrics such as the network degree can be used to estimate wellbeing at a national level. In this section, we further examine the connectedness between pairs of countries through community structure across network layers as a form of socioeconomic similarity. We use the Louvain modularity optimisation method [40] for community detection in each individual network,PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,14 /The International Postal Network and Other Global Flows as Proxies for National WellbeingFig 8. Country community membership for each network. doi:10.1371/journal.pone.0155976.gwhich takes into account the tie strength of relationships between countries and finds the optimal split in terms of disconnectedness in the international network. This returns between 4? communities for each network, the geographical distribution of which is shown in Fig 8. Although communities naturally seem to be very driven by geography in physical flow networks, this is not the case in digital networks where communities are geographically dispersed. This is an indication of the difference in the way countries connect through post, trade, migration and flights rather than on the IP and social media networks. However, what does it mean for two countries to be both members of the same network community? Common community membership indicates a level of connectedness between two countries, which is beyond the randomly expected for the network. It is often observed that nodes in the same communities share many similar properties, therefore it can be expected that pairs of nodes which share multiple communities across networks are even more similar. In this work, we measure the overlap in pairwise membership between pairs of countries across our six networks as the community multiplexity index, a measure of socioeconomic similarity. Our hypothesis is that countries that are paired together in communities across more networks are more likely to be socioeconomically similar. We measure similarity here as the absolute difference between each indicator from the previous section for two countries and plot that against their community multiplexity. For example, the United States has an average life expectancy of 70 years, whereas Afghanistan has an average life expe.

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known

.pone.0119985.gAs expected, childhood maltreatment was associated with several covariates known to be related to BMI (Table 3). Some covariates such as unemployment and smoking have been shown in the literature to be negatively associated with BMI, e.g. on average, smokers have a lower BMI [11]. In our study such characteristics were more common among maltreated groups: e.g., prevalence of smoking and unemployment 23y to 50y was higher in the maltreated than nonmaltreated (Table 3). Potentially, these differences would lower the adult BMI among those exposed to childhood maltreatment. Allowance for such factors and their changes over time, as well as other covariates, is important for understanding associations with BMI at specific ages and BMI trajectories. Modelled lifetime trajectories of zBMI and obesity risk (Table 4 and S2 Table) confirmed the ICG-001 cancer patterns with age suggested by simple analyses.Childhood abuseIn both genders there was a positive linear association between zBMI gain with age and physical abuse, by 0.006/y (males) and 0.007/y (females) after adjustment for all Vorapaxar web covariatesPLOS ONE | DOI:10.1371/journal.pone.0119985 March 26,7 /Child Maltreatment and BMI TrajectoriesTable 3. Characteristics of those with no childhood maltreatment and those abused or neglected ( ). Abuse Non-maltreated Males

Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC

Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC, INBIO, INHS, NMNH). COSTA RICA, ACG database codes: See GLPG0187MedChemExpress GLPG0187 Appendix 2 for detailed label data. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: tegula pale, humeral complex half pale/half dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least PP58 site extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Fore wing length: 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.3?.5, rarely 2.0?.2. Interocellar distance/ posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.2?.3. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with punctures near margins, central part mostly smooth. Number of pits in scutoscutellar sulcus: 5 or 6 or 7 or 8. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.4?0.5. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: mostly sculptured. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 2.8?.1. Mediotergite 2 sculpture: mostly smooth. Outer margin of hypopygium: with a wide, medially folded,Review of Apanteles sensu stricto (Hymenoptera, Braconidae, Microgastrinae)…transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.6?.7, rarely 1.2?.3. Length of fore wing veins r/2RS: 1.7?.9. Length of fore wing veins 2RS/2M: 0.9?.0. Length of fore wing veins 2M/(RS+M)b: 0.9?.0. Pterostigma length/width: 3.6 or more. Point of insertion of vein r in pterostigma: clearly beyond half way point length of pterostigma. Angle of vein r with fore wing anterior margin: clearly outwards, inclined towards fore wing apex. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. As in female but with darker legs and smoother mediotergite 1. Molecular data. Sequences in BOLD:.Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC, INBIO, INHS, NMNH). COSTA RICA, ACG database codes: See Appendix 2 for detailed label data. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: tegula pale, humeral complex half pale/half dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Fore wing length: 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.3?.5, rarely 2.0?.2. Interocellar distance/ posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.2?.3. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with punctures near margins, central part mostly smooth. Number of pits in scutoscutellar sulcus: 5 or 6 or 7 or 8. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.4?0.5. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: mostly sculptured. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 2.8?.1. Mediotergite 2 sculpture: mostly smooth. Outer margin of hypopygium: with a wide, medially folded,Review of Apanteles sensu stricto (Hymenoptera, Braconidae, Microgastrinae)…transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.6?.7, rarely 1.2?.3. Length of fore wing veins r/2RS: 1.7?.9. Length of fore wing veins 2RS/2M: 0.9?.0. Length of fore wing veins 2M/(RS+M)b: 0.9?.0. Pterostigma length/width: 3.6 or more. Point of insertion of vein r in pterostigma: clearly beyond half way point length of pterostigma. Angle of vein r with fore wing anterior margin: clearly outwards, inclined towards fore wing apex. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. As in female but with darker legs and smoother mediotergite 1. Molecular data. Sequences in BOLD:.

‘ coordinate is the percentage of roles (s)he accepted for each

‘ coordinate is the percentage of roles (s)he CV205-502 hydrochloride site accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary VadadustatMedChemExpress Vadadustat FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.’ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.

A six-min incubation with Gentle Cell Dissociation Reagent followed by complete

A six-min incubation with Gentle Cell Dissociation Reagent followed by complete physical dispersions by ONO-4059 dose repeated pipetting. Large cells (>70 m) were then collected by passing the suspension successively through a series of nylon cell strainers (70 m and 40 m, Fisher Scientific) to GW 4064 msds generate three cell size fractions (>70 m, 40?0 m, and <40 m). The captured cells on the strainer were recovered by inverting the strainer and rinsing with culture medium. Similarly, middle size cells (40?0 m) were obtained from the <70-m fraction by collection on a 40-m cell strainer after removal of <70-m cells. The three size fractions were used in all subsequent analyses. Portions of the size-fractioned cells were fixed in 4 (vol/vol) paraformaldehyde/PBS solution for 15 min and resuspended (5.0 ?102 and 1.0 ?105 cells/100 L PBS). The suspensions were loaded into a Shandon single cytofunnel and centrifuged for 5 min at 1,000 ?g in a Shandon CytoSpin 4 cytocentrifuge (Thermo Scientific). Derivation Primary Human PHTu and PHTd. Placental tissue samples were collected by the Obstetrical Specimen Procurement Unit at Magee-Womens Hospital of the University of Pittsburgh Medical Center. The work was performed under an exempt protocol approved by the Institutional Review Board (IRB) at the University of Pittsburgh. Under the protocol, patients provided written consent for the use of deidentified discarded tissues for research upon admittance to the hospital. Primary villous PHTs were derived and cultured according to published procedures (12, 49, 50) from three term human placentas (one female and two males). Multiple primary cultures were established from each placenta at a density of 3.5 ?105 cells/cm2 in DMEM supplemented with 10 (vol/vol) FBS and antibiotics under a 5 (vol/vol) CO2/air atmosphere at 37 . Triplicate cultures from each placenta were harvested at 9 h (PHTu) before syncytium formation and subsequently at 48 h (PHTd) when syncytium formation had occurred. The sieving technique used for the hESC-derived cells was thus unnecessary for the term placental STB. Total RNA was extracted from each sample (3 ?3 at 9 h and 48 h, respectively) to provide a total of 18 samples for RNA-seq analysis. Additional methods are described in SI Appendix, SI Materials and Methods. ACKNOWLEDGMENTS. We thank L. C. Schulz for her critical reading of the manuscript and her helpful comments; N. J. Bivens for RNA-seq; W. Spollen, C. Bottoms, and S. Givan for their sequence data analysis; Y. Tian for immunoassays; A. Jurkevich for technical assistance; M. Schauflinger, D. Grant, and T. A. White for sharing equipment; and D. F. Reith for his editorial assistance and administrative support. This study was supported by NIH Grant R01HD077108 (to T.E. and D.J.S.) and Grant R01HD067759 (to R.M.R.).7. Loke YW, King A (1995) Human Implantation: Cell Biology and Immunology (Cambridge Univ Press, Cambridge). 8. Miller RK, et al. (2005) Human placental explants in culture: Approaches and assessments. Placenta 26(6):439?48. 9. Sim CM, Sibley CP, Jones CJ, Turner MA, Greenwood SL (2001) The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am J Physiol Regul Integr Comp Physiol 280(4):R1116 1122. 10. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186(2):306?16. 11. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B (2010) The choriocarcinoma cell line BeW.A six-min incubation with Gentle Cell Dissociation Reagent followed by complete physical dispersions by repeated pipetting. Large cells (>70 m) were then collected by passing the suspension successively through a series of nylon cell strainers (70 m and 40 m, Fisher Scientific) to generate three cell size fractions (>70 m, 40?0 m, and <40 m). The captured cells on the strainer were recovered by inverting the strainer and rinsing with culture medium. Similarly, middle size cells (40?0 m) were obtained from the <70-m fraction by collection on a 40-m cell strainer after removal of <70-m cells. The three size fractions were used in all subsequent analyses. Portions of the size-fractioned cells were fixed in 4 (vol/vol) paraformaldehyde/PBS solution for 15 min and resuspended (5.0 ?102 and 1.0 ?105 cells/100 L PBS). The suspensions were loaded into a Shandon single cytofunnel and centrifuged for 5 min at 1,000 ?g in a Shandon CytoSpin 4 cytocentrifuge (Thermo Scientific). Derivation Primary Human PHTu and PHTd. Placental tissue samples were collected by the Obstetrical Specimen Procurement Unit at Magee-Womens Hospital of the University of Pittsburgh Medical Center. The work was performed under an exempt protocol approved by the Institutional Review Board (IRB) at the University of Pittsburgh. Under the protocol, patients provided written consent for the use of deidentified discarded tissues for research upon admittance to the hospital. Primary villous PHTs were derived and cultured according to published procedures (12, 49, 50) from three term human placentas (one female and two males). Multiple primary cultures were established from each placenta at a density of 3.5 ?105 cells/cm2 in DMEM supplemented with 10 (vol/vol) FBS and antibiotics under a 5 (vol/vol) CO2/air atmosphere at 37 . Triplicate cultures from each placenta were harvested at 9 h (PHTu) before syncytium formation and subsequently at 48 h (PHTd) when syncytium formation had occurred. The sieving technique used for the hESC-derived cells was thus unnecessary for the term placental STB. Total RNA was extracted from each sample (3 ?3 at 9 h and 48 h, respectively) to provide a total of 18 samples for RNA-seq analysis. Additional methods are described in SI Appendix, SI Materials and Methods. ACKNOWLEDGMENTS. We thank L. C. Schulz for her critical reading of the manuscript and her helpful comments; N. J. Bivens for RNA-seq; W. Spollen, C. Bottoms, and S. Givan for their sequence data analysis; Y. Tian for immunoassays; A. Jurkevich for technical assistance; M. Schauflinger, D. Grant, and T. A. White for sharing equipment; and D. F. Reith for his editorial assistance and administrative support. This study was supported by NIH Grant R01HD077108 (to T.E. and D.J.S.) and Grant R01HD067759 (to R.M.R.).7. Loke YW, King A (1995) Human Implantation: Cell Biology and Immunology (Cambridge Univ Press, Cambridge). 8. Miller RK, et al. (2005) Human placental explants in culture: Approaches and assessments. Placenta 26(6):439?48. 9. Sim CM, Sibley CP, Jones CJ, Turner MA, Greenwood SL (2001) The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am J Physiol Regul Integr Comp Physiol 280(4):R1116 1122. 10. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186(2):306?16. 11. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B (2010) The choriocarcinoma cell line BeW.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases get SC144 George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Nilotinib mechanism of action Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

His flexibility in order to achieve certain caregiving ends. Yet this

His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and BAY 11-7083MedChemExpress BAY 11-7083 Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing Pyrvinium embonate supplement history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.His flexibility in order to achieve certain caregiving ends. Yet this flexibility is shaped by structural conditions that also create significant challenges for caregivers. Generalized poverty, a significant decline in bridewealth practices, and women’s increased access to education, land, and cash income all serve to make marriage more easily dissolvable or even less desirable to begin with. This lessens the power and appeal of patrilineal fosterage patterns. These trends are economically and ideologically ambiguous as maternal kin increasingly have both the burden and the privilege of caring for their daughters’ children, while children have narrowed options for receiving support. According to the ‘official kin’, the rules of child fostering are rigid and fixed. In practice, however, fostering allows for a wide array of household configurations that are negotiated based on a range of competing ideologies. As Alber notes in her study of child fostering in Benin, the lived experiences of people are ‘more flexible and varied than the rules suggest’ (2004: 36). Caregivers who are trying to legitimate their right to care for a child emphasize the rigidity of the rules because it allows them strategically to point to the ways in which others are contravening the rules. Comaroff suggests that negotiations around power are ‘mediated by the properties of a specific set of rules’ (1978: 17).While his study examines the claims to power of Tswana chiefs, I argue that these same processes are replicated on a smaller scale in the negotiations over relatedness that occur in everyday life in Lesotho. Matrilocal caregivers are able to negotiate for the care of children while maintaining the dominant ideology of patrilineal care. In doing so, caregivers have been able to manipulate the tenets of ‘official kin’ in order to achieve a range of caregiving outcomes, many of which legitimate matrilocal care within the patrilineal system. While these shifting values have markedly changed the caregiving landscape, they have yet to be formally institutionalized precisely because of the focus on patrilineality. In this way, maternal kin are reinforcing the patriarchal structure of the Basotho family in order to privilege their role as caregivers.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageAcknowledgmentsThis research was funded by the W.K. Kellogg Family Fellowship in Children and Families and the Population Studies and Training Center (PSTC) at Brown University. The PSTC receives core support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R24HD041020). I would like to thank MCS staff and caregivers for all their help and support. I am grateful to my writing group at Brown (Adia Benton, Melissa Hackman, and Jennifer Stampe), and to Jessaca Leinaweaver and Mandy Terc for reading earlier versions of this article. Thank you to Justin Dyer for his careful copy-editing.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Female sex workers (FSWs) in China: social and behavioural studies and HIV prevention strategies Female sex work has a long-standing history in China as an integrated facet of social and economic life (Hershatter, 1997; Pan, 1997). Sex work became more visible in China starting in the late 1980s due to regular, government-ordered anti-prostitution crackdowns and growing epidemics of HI.

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the PNPP manufacturer qualitative component? Are the study context and L 663536 web objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.

Preservation (butylated hydroxytoluene).112 The coverage in this section is not intended

Preservation (butylated hydroxytoluene).112 The coverage in this section is not intended to be complete, but is rather focused on representative cases where there are extensive pKa, E, and bond strength data. A reader interested in a particular substituted derivative that does not appear in Table 4 is encouraged to check the references cited there, and reference 56, as many of the primary papers cover a range of substituents.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Page5.2.1 Phenol (PhOH)–Phenol has been widely studied as the simplest of the aromatic hydroxylic compounds. The gas-phase O BDE in phenol has been a subject of much discussion.62,113,114 Heats of formation from the NIST Chemistry WebBook, Hf as(PhO? = 13 ?1 kcal mol- and Hf as(PhOH =-23.03 ?0.14 kcal mol-1, give BDEg(PhOH) = 88.0 ?1 kcal mol-1.49,70 This value is in between alternative values of 86.7 kcal mol-1 114 and 88.7 kcal mol-1.62 A clearer value for this important benchmark compound would be valuable. A wealth of thermochemical data is available for phenols, in particular their acidity [pKa(ArOH)] and the phenoxyl radical/phenoxide reduction [E?ArO?-)]. Protonated phenoxyl radicals are typically high energy species with aqueous pKa values > 0.115 The most extensive studies of E?ArO?-) are by Bordwell et al. for DMSO solutions116 and by Lind et al. and Steenken and Neta in aqueous media.117,118 The aqueous measurements take advantage of the phenol potential becoming independent of pH above its pKa (see Section 3.2 above). Phenols readily react by hydrogen atom transfer (HAT) and this pathway is implicated in the antioxidant properties of phenols both in vivo and in vitro (see below).119 For the more acidic phenols, or under basic conditions, a mechanism of sequential proton loss then electron transfer (SPLET) can occur.11?213 It is less common for phenols to react by initial outer-sphere electron transfer because of the high E?PhOH?/0) potentials. The ArO? ArOH potentials (or, better, BDFEs) are often above the thermodynamic requirement for water oxidation, as is necessary for the function of Tyrosine Z in photosystem II, mediating hole transfer from the chlorophyll radical cation to the oxygen evolving complex. 5.2.2 2,4,6-Tri-tert-butylphenol (tBu3PhOH)–4-Substituted-2,6-di-tert-butyl-phenols are widely used in the research lab and as food preservatives, especially `butylated hydroxytoluene’ (BHT, 4-Me) and `butylated hydroxyanisole’ (BHA, 4-MeO). 2,4,6-tBu3PhOH is an especially interesting and useful reagent for studies of PCET reactions because of the exceptional stability of the phenoxyl radical (tBu3PhO?.120 The radical is easily prepared from the corresponding phenol using NaOH and K3Fe(CN)6, and can be isolated as dark blue crystals.120 As discussed for TEMPOH above, we have recently reevaluated the solution BDE of tBu3PhO?in C6H6 to account for recent revision of the thermochemistry of the Chloroquine (diphosphate) site originally used diphenylhydrazine/azobenzene couple.40 Our preferred value is 81.6 ?0.4 kcal mol-1. The tBu3PhO(?H) PCET couple is a very useful benchmark for the determination of bonds strengths in other phenols. The clearest example is Pedulli and co-workers’ EPR method to measure equilibrium buy Sitravatinib constants for ArOH + tBu3PhO?121 Please note that here and in Table 4, we have slightly adjusted Pedulli’s reported BDEs to reflect our recent critical evaluation of the BDE.Preservation (butylated hydroxytoluene).112 The coverage in this section is not intended to be complete, but is rather focused on representative cases where there are extensive pKa, E, and bond strength data. A reader interested in a particular substituted derivative that does not appear in Table 4 is encouraged to check the references cited there, and reference 56, as many of the primary papers cover a range of substituents.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Page5.2.1 Phenol (PhOH)–Phenol has been widely studied as the simplest of the aromatic hydroxylic compounds. The gas-phase O BDE in phenol has been a subject of much discussion.62,113,114 Heats of formation from the NIST Chemistry WebBook, Hf as(PhO? = 13 ?1 kcal mol- and Hf as(PhOH =-23.03 ?0.14 kcal mol-1, give BDEg(PhOH) = 88.0 ?1 kcal mol-1.49,70 This value is in between alternative values of 86.7 kcal mol-1 114 and 88.7 kcal mol-1.62 A clearer value for this important benchmark compound would be valuable. A wealth of thermochemical data is available for phenols, in particular their acidity [pKa(ArOH)] and the phenoxyl radical/phenoxide reduction [E?ArO?-)]. Protonated phenoxyl radicals are typically high energy species with aqueous pKa values > 0.115 The most extensive studies of E?ArO?-) are by Bordwell et al. for DMSO solutions116 and by Lind et al. and Steenken and Neta in aqueous media.117,118 The aqueous measurements take advantage of the phenol potential becoming independent of pH above its pKa (see Section 3.2 above). Phenols readily react by hydrogen atom transfer (HAT) and this pathway is implicated in the antioxidant properties of phenols both in vivo and in vitro (see below).119 For the more acidic phenols, or under basic conditions, a mechanism of sequential proton loss then electron transfer (SPLET) can occur.11?213 It is less common for phenols to react by initial outer-sphere electron transfer because of the high E?PhOH?/0) potentials. The ArO? ArOH potentials (or, better, BDFEs) are often above the thermodynamic requirement for water oxidation, as is necessary for the function of Tyrosine Z in photosystem II, mediating hole transfer from the chlorophyll radical cation to the oxygen evolving complex. 5.2.2 2,4,6-Tri-tert-butylphenol (tBu3PhOH)–4-Substituted-2,6-di-tert-butyl-phenols are widely used in the research lab and as food preservatives, especially `butylated hydroxytoluene’ (BHT, 4-Me) and `butylated hydroxyanisole’ (BHA, 4-MeO). 2,4,6-tBu3PhOH is an especially interesting and useful reagent for studies of PCET reactions because of the exceptional stability of the phenoxyl radical (tBu3PhO?.120 The radical is easily prepared from the corresponding phenol using NaOH and K3Fe(CN)6, and can be isolated as dark blue crystals.120 As discussed for TEMPOH above, we have recently reevaluated the solution BDE of tBu3PhO?in C6H6 to account for recent revision of the thermochemistry of the originally used diphenylhydrazine/azobenzene couple.40 Our preferred value is 81.6 ?0.4 kcal mol-1. The tBu3PhO(?H) PCET couple is a very useful benchmark for the determination of bonds strengths in other phenols. The clearest example is Pedulli and co-workers’ EPR method to measure equilibrium constants for ArOH + tBu3PhO?121 Please note that here and in Table 4, we have slightly adjusted Pedulli’s reported BDEs to reflect our recent critical evaluation of the BDE.

N scan or take a photo of the object in their

N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and GLPG0187 supplier annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to JWH-133MedChemExpress JWH-133 evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.N scan or take a photo of the object in their workplace, task, or virtual case, and the real object will be integrated in MARE. GP behavior can be tracked and their skill within the knowledge level tested. For example, KS1 involves obtaining microbiological cultures or other relevant tests before starting treatment as necessary. A patient who has bacterial pneumonia or viral pneumonia will be shown to a GP treating in MARE. The GP will either select laboratory tests and interpret results or not. We will know whether the GP achieves KS1 or not. The KC of GPs can also be evaluated in MARE. GPs can write instant messages, comment, and annotate that they understand the rational use of antibiotics. GPs can also categorize, tag, or highlight the information that they think is correct. For example, KC2 is recognizing trade and generic names, and the class of prescribed antimicrobials. GPs can categorize the class of prescribed antimicrobials when using MARE to scan trade or generic names.Competence LevelThe competence level expected of GPs regarding rational use of antibiotics is described in Table 2. Emotions and values not only affect the application of knowledge but are also a foundation for building GP competence according to physicians’ professional competence definitions [34]. When we use MARE to evaluate GPs’ competence levels, the cases could be conducted in mixed real environments (eg, the real person and the symptom described coexist on the GP’s mobile phone in his or her workplace). The procedure for forecasting, executing, or replying can be uploaded to evaluate the GP’s CC and CS. For example, CC4 is constructing a prescription for an antimicrobial with its pharmacokinetics and knowing how this affects the choice of dosage regimen. The case condition will change when different antimicrobials are used with their pharmacokinetics. The result for the forecasting of antibiotics by the GP and the dosage regimen will be evaluated.Application of Mobile Augmented Reality Education to a Health Care ChallengeIn recent years, one of the global health threats has been the spread of antibiotic resistance. Encouraging rational antibiotic use is of paramount concern to authorities worldwide in order to minimize the development of resistance [50]. Multifaceted national and international strategies have been recommended [51]. Education is an important strategy for the rational use of antibiotics. We used the MARE framework to design GP training for the rational use of antibiotics. Implementing the MARE framework involves several steps: (1) defining the educational outcomes (based on the outcome layer), (2) defining the GP’s personal paradigm, (3) characterizing the learning environment, and (4) designing the learning activities.Performance LevelThe performance level expected of GPs regarding the rational use of antibiotics is shown in Table 3. To aid GPs in assessing their workplace performance using the MARE framework, we should build a network for physicians in which they can share their work experiences; then the GPs can review, question, and validate their work performances with each other. Further, the GPs can negotiate, debate, and comment on real cases, and their performance in skills, such as PC and PS, can be tracked and estimated. For example, PS2 is mastering when to use a delayed antimicrobial prescription and how to negotiate this with the patient. One way is to evaluate the GP’s response with the patient case shared on MARE with othe.

Een the subject of intensive breeding programs. For instance, the Churra

Een the subject of intensive breeding programs. For instance, the Churra breed has experienced a 15?0 increase in milk production during the last 25 years (Churra Breeding Association web, http://www.anche.org). In the light of these facts, we expected to find selective sweeps related with meat vs milk production in our dataset. When we built a population tree based on SNPs mapping to the three selective sweeps, we did not observe a clustering of the Churra and Latxa dairy breeds, though they were located in close positions (Supplementary Fig. S2). Consistently, local trees based on SNPs that mapped to the Oar3 and Oar6 selective sweeps did not show a clustering of Churra and Latxa. In contrast, both breeds grouped together in the local tree based on SNPs located within the Oar13 selective sweep. Moreover, the analysis of the allele frequencies of SNPs mapping to the Oar3, Oar6 and Oar13 selective sweeps did not reveal any meaningful pattern (Supplementary Fig. S3). These inconclusive results could be due to the limited power and the stringency of our experiment. We may have missed many selective sweeps that did not reach statistical significance due to the moderate sample size employed in our study or because they were not simultaneously identified with BayeScan and hapFLK. Genetic heterogeneity amongst breeds, where distinct mutations have similar effects on milk yield or growth, could be another reason. It is also possible that the selective sweeps we have detected do not have any relationship with meat or milk production but with other traits (e.g. morphology, adaptation, SB 202190 web reproduction, disease resistance) that we did not take into consideration in our order Synergisidin selection analysis. A fourth factor could be that artificial selection for meat and dairy traits has mainly evolved through polygenic adaptation, shifting the allele frequencies of hundreds or thousands of loci instead of fixing novel mutations with major phenotypic effects. Finally, the methods used by us are good at detecting ongoing or recently completed selective sweeps but they have difficulties in identifying ancient sweeps that ended a long time ago40. Though we have found patterns of variation on Oar3, Oar6, and Oar13 that are compatible with the occurrence of selective sweeps, it is difficult to envisage which set of phenotypes were really targeted by selection. Indeed, intensive selection of Spanish sheep breeds, as Churra and Latxa, for milk production is relatively recent (it began 2? decades ago) and genetic exchanges between dairy and non-dairy populations may have taken place, thus obscuring the effects of selection. Importantly, several of the selective sweeps detected with BayeScan and hapFLK contained genes encoding transcriptional regulators with effects on body size (e.g. HGMA2 on Oar3 and LCORL and NCAPG on Oar6). This phenotype experienced a substantial reduction during the early times of domestication and subsequently increased as a consequence of artificial selection for growth rate. Changes in the selection pressure conferring a higher biological efficacy to a mutation that was previously deleterious are expected to generate hard sweep signatures41. Our finding, however, is difficult to interpret because the set of breeds employed in the current work do not differ substantially in terms of body size, weight or stature. Such cryptic selective sweeps have been also observed in cattle41, and so far their biological significance remains unknown. Noteworthy, neutra.Een the subject of intensive breeding programs. For instance, the Churra breed has experienced a 15?0 increase in milk production during the last 25 years (Churra Breeding Association web, http://www.anche.org). In the light of these facts, we expected to find selective sweeps related with meat vs milk production in our dataset. When we built a population tree based on SNPs mapping to the three selective sweeps, we did not observe a clustering of the Churra and Latxa dairy breeds, though they were located in close positions (Supplementary Fig. S2). Consistently, local trees based on SNPs that mapped to the Oar3 and Oar6 selective sweeps did not show a clustering of Churra and Latxa. In contrast, both breeds grouped together in the local tree based on SNPs located within the Oar13 selective sweep. Moreover, the analysis of the allele frequencies of SNPs mapping to the Oar3, Oar6 and Oar13 selective sweeps did not reveal any meaningful pattern (Supplementary Fig. S3). These inconclusive results could be due to the limited power and the stringency of our experiment. We may have missed many selective sweeps that did not reach statistical significance due to the moderate sample size employed in our study or because they were not simultaneously identified with BayeScan and hapFLK. Genetic heterogeneity amongst breeds, where distinct mutations have similar effects on milk yield or growth, could be another reason. It is also possible that the selective sweeps we have detected do not have any relationship with meat or milk production but with other traits (e.g. morphology, adaptation, reproduction, disease resistance) that we did not take into consideration in our selection analysis. A fourth factor could be that artificial selection for meat and dairy traits has mainly evolved through polygenic adaptation, shifting the allele frequencies of hundreds or thousands of loci instead of fixing novel mutations with major phenotypic effects. Finally, the methods used by us are good at detecting ongoing or recently completed selective sweeps but they have difficulties in identifying ancient sweeps that ended a long time ago40. Though we have found patterns of variation on Oar3, Oar6, and Oar13 that are compatible with the occurrence of selective sweeps, it is difficult to envisage which set of phenotypes were really targeted by selection. Indeed, intensive selection of Spanish sheep breeds, as Churra and Latxa, for milk production is relatively recent (it began 2? decades ago) and genetic exchanges between dairy and non-dairy populations may have taken place, thus obscuring the effects of selection. Importantly, several of the selective sweeps detected with BayeScan and hapFLK contained genes encoding transcriptional regulators with effects on body size (e.g. HGMA2 on Oar3 and LCORL and NCAPG on Oar6). This phenotype experienced a substantial reduction during the early times of domestication and subsequently increased as a consequence of artificial selection for growth rate. Changes in the selection pressure conferring a higher biological efficacy to a mutation that was previously deleterious are expected to generate hard sweep signatures41. Our finding, however, is difficult to interpret because the set of breeds employed in the current work do not differ substantially in terms of body size, weight or stature. Such cryptic selective sweeps have been also observed in cattle41, and so far their biological significance remains unknown. Noteworthy, neutra.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of Aprotinin price social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms AZD4547 manufacturer dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.

T the funeral … they said that I should take the child.

T the Mangafodipir (trisodium) biological activity funeral … they said that I should take the child. And I said, how will I take the child yet I’m sick? And the thieves have taken all my animals. And at least there, he will have milk to eat, and I refused to take him … this child is yours not mine. And after I buried the mother, three days passed … they came and brought this baby saying their mother said this child is supposed to be here …Yet I said I don’t need him. And they left him. He was very sick. He was very sick. He nearly died … ‘M’e Masello highlights the complexity of fostering AIDS orphans. She felt that she did not have the resources or physical capabilities to care for Lebo and his siblings, yet there was no one else willing to care for them. The children were left with her after lengthy discussions between the two families and their chiefs. However, this does not indicate any lack of love or affection for the children on her part. She was particularly close with Lebo. She often emphasized how happy she was to be living with the children, and how much they helped her. Nevertheless, although she was deemed most capable of caring for Lebo and his siblings, this did not mean that they were ensured adequate care. Although, initially, ‘M’e Masello was physically and mentally able to provide for the children, for the last year of her life she was unable to give them the care they needed. This was especially true for Lebo, whose HIV regimen was particularly complex owing to numerous misdiagnoses. As a result of his grandmother’s sickness, his adherence to his antiretroviral treatment declined. I learned recently that ‘M’e Masello had died. Now the struggle to find a caregiver for the children has begun again.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptConclusionA history of dependence on migrant labour, changing marriage practices, and HIV/ AIDS have altered kin-based fostering networks among Basotho families. More children are in need of care, yet there are fewer caregivers to provide it. In rural communities, whereJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageinstitutionalized care is unavailable and external support is limited, kin-based care is the only option. In order to cope with these pressures, families are organizing themselves by focusing their resources matrilocally. Yet they are making sense of this model of care within the patrilineal system of child fostering. This is most evident in the ways purchase BAY 11-7083 family members negotiate for the care of children. In particular, primarily elderly female caregivers attempt to demonstrate their right to the children, often focusing on the presence or absence of bridewealth as key to their negotiation strategies. Simultaneously, there is an overriding emphasis on the quality of care that potential caregivers can provide (Ksoll 2007). The day-to-day role of women in this system has not drastically changed: women still do the majority of the care work. In fact, women are being called upon to care for an increased number of children — including those with greater health problems — yet with diminishing resources. What has changed, however, is the role a woman’s natal family plays in supporting her. In a context where marriage is a risk factor for contracting HIV (Smith 2007), but where having children still holds significant social value (Booth 2004), an easily dissolvable marriage may be seen as advantageous by mothers and maternal grandmothers, who can manipulate t.T the funeral … they said that I should take the child. And I said, how will I take the child yet I’m sick? And the thieves have taken all my animals. And at least there, he will have milk to eat, and I refused to take him … this child is yours not mine. And after I buried the mother, three days passed … they came and brought this baby saying their mother said this child is supposed to be here …Yet I said I don’t need him. And they left him. He was very sick. He was very sick. He nearly died … ‘M’e Masello highlights the complexity of fostering AIDS orphans. She felt that she did not have the resources or physical capabilities to care for Lebo and his siblings, yet there was no one else willing to care for them. The children were left with her after lengthy discussions between the two families and their chiefs. However, this does not indicate any lack of love or affection for the children on her part. She was particularly close with Lebo. She often emphasized how happy she was to be living with the children, and how much they helped her. Nevertheless, although she was deemed most capable of caring for Lebo and his siblings, this did not mean that they were ensured adequate care. Although, initially, ‘M’e Masello was physically and mentally able to provide for the children, for the last year of her life she was unable to give them the care they needed. This was especially true for Lebo, whose HIV regimen was particularly complex owing to numerous misdiagnoses. As a result of his grandmother’s sickness, his adherence to his antiretroviral treatment declined. I learned recently that ‘M’e Masello had died. Now the struggle to find a caregiver for the children has begun again.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptConclusionA history of dependence on migrant labour, changing marriage practices, and HIV/ AIDS have altered kin-based fostering networks among Basotho families. More children are in need of care, yet there are fewer caregivers to provide it. In rural communities, whereJ R Anthropol Inst. Author manuscript; available in PMC 2015 April 08.BlockPageinstitutionalized care is unavailable and external support is limited, kin-based care is the only option. In order to cope with these pressures, families are organizing themselves by focusing their resources matrilocally. Yet they are making sense of this model of care within the patrilineal system of child fostering. This is most evident in the ways family members negotiate for the care of children. In particular, primarily elderly female caregivers attempt to demonstrate their right to the children, often focusing on the presence or absence of bridewealth as key to their negotiation strategies. Simultaneously, there is an overriding emphasis on the quality of care that potential caregivers can provide (Ksoll 2007). The day-to-day role of women in this system has not drastically changed: women still do the majority of the care work. In fact, women are being called upon to care for an increased number of children — including those with greater health problems — yet with diminishing resources. What has changed, however, is the role a woman’s natal family plays in supporting her. In a context where marriage is a risk factor for contracting HIV (Smith 2007), but where having children still holds significant social value (Booth 2004), an easily dissolvable marriage may be seen as advantageous by mothers and maternal grandmothers, who can manipulate t.

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on

N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is Leupeptin (hemisulfate)MedChemExpress Leupeptin (hemisulfate) important to note the objective of this get BAY1217389 review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.N sub-Saharan AfricaYesSomewhatNo?For mixed-methods studies, is there sufficient emphasis on the qualitative component? Are the study context and objectives clearly described?Study setting adequately described? Rationale for conducting the study stated and justified? Is there evidence of researcher reflexivity????Researcher’s role, potential bias and influence on respondents examined in formulation of questions, data collection and data analysis? Is the recruitment strategy appropriate to the study aims? Researcher explained how study informants were selected? Discussion around recruitment, i.e. why some people chose not to take part? Is the method of data collection clearly described and appropriate for the research question? Data collection method explicitly stated? Saturation of data discussed? Is the data analysis sufficiently rigorous?????Analytic process described in sufficient detail? If thematic analysis is used, is it clear how themes/categories were derived? Are contradictory data taken into account? Are conclusions supported by sufficient evidence??????Did the data provide sufficient depth, detail and richness? The researcher discussed credibility of their findings (triangulation, respondent validation, more than one analyst)?*Screening question, captured in inclusion criteria.on how informants’ responses or subsequent data analysis may have been influenced by the role of the research team. These observations are not unique to our literature review. As pointed out by Glenton et al. (2013) in a Cochrane qualitative literature review, qualitative articles published in journals tend to provide relatively `thin’ data and are less likely to include a variety of data gathering methods. Glenton and others also reported lack of researcher reflexivity as a common finding when qualitative studies are being appraised. Longitudinal, ethnographic research may be better suited to qualitative studies that examine health interventions (Pawson et al. 2005, Glenton et al. 2013, Dawson et al. 2014), but such research is more time and resource demanding and often too extensive to be published in widely circulated health research journals. Thus, all the studies meeting the original inclusion criteria were included in the subsequent analysis regardless of the quality score assigned. Although some studies were deemed to be of lower methodological quality, the insights from stakeholders they presented nevertheless contributed to the richness of data and were informative for data synthesis. This is one of the approaches commonly adopted in qualitative reviews, especially when there are a limited number of studies available (Pawson et al. 2005, Hannes 2011).Data abstractionFollowing Thomas and Harden (2008), a thematic synthesis approach was used to compile the data. In following this approach, it is important to note the objective of this review ?to inform the study of task shifting for work being developed in Kenya. Given this aim, we were interested in `key concepts’ (Campbell et al. 2003) that might illuminate the characteristics of effective task-shifting programmes while highlighting the major barriers to implementation. Of course, we also needed to remain true to the texts we examined, all of the noted facets of implementation and the character of the reformed systems studied. In this way, although our aims were pragmatic and directed towards the needs of our future project, we were also aiming to provide as much `thick description’ as possible.

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides

(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, Tariquidar site discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 –get Zebularine tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.(and the BDFE) of tBu3PhOH.40 The EPR equilibration method provides a high degree of precision and the values are, in general, internally consistent.122 The values obtained agree very well with those from other methods, such as from E?and pKa measurements. For example, the adjusted Pedulli values for BDFE(PhOH) and BDFE(2,6-tBu2PhOH) in C6H6, = 83.8 and 78.3 kcal mol-1 (Table 4), agree very closely with our conversion of Bordwell’s BDFEs in DMSO (from E?and pKa values)116 to C6H6 using the Abraham method, 83.7 and 78.1 kcal mol-1, respectively. 5.2.3 Tyrosine–Redox reactions of the amino acid tyrosine are involved in biological energy transduction, charge transport, oxidative stress, and enzymatic catalysis.123 The 1H+/1e- oxidized form, the tyrosyl radical, has been implicated in a variety of enzymatic systems, including ribonucleotide reductases,109 photosystem II,106 galactose oxidase,124 prostaglandin-H-synthase125 and perhaps cytochrome c oxidase.126 Furthermore, tyrosineNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptChem Rev. Author manuscript; available in PMC 2011 December 8.Warren et al.Pageoxidation products are thought to play deleterious roles in various disease states, including atherosclerosis and aging.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe proton-coupled redox chemistry of tyrosine (TyrOH) and related compounds has been widely reported.128?29130131 In aqueous solutions, the Pourbaix diagram shows a clear 59 mV per pH dependence for the oxidation of tyrosine below pH 10, indicative of a 1e-/ 1H+ redox couple. As for phenol, above pKa(tyrosine) the redox potential does not depend on pH because this is the proton-independent TyrO?TyrO- redox couple. Other, more detailed, discussions of aspects of proton-coupled redox chemistry of tyrosine can be found in other contributions to this issue. As an aside, we encourage biochemical studies of PCET to use a nomenclature that explicitly shows the proton, such as `TyrOH’ for tyrosine, to avoid ambiguity. For instance, the commonly used “Y? for tyrosyl radicals could refer either to neutral radical TyrO?or to the typically high-energy radical cation TyrOH?. 5.2.4 -Tocopherol and Related Phenols—Tocopherol (a main component of Vitamin E) is thought to be a key chain breaking antioxidant in biological systems. Since its discovery in 1922,132 vitamin E has received considerable attention from chemists, biologists, and clinicians, among others.110 Due to its insolubility in water, several small water soluble analogs such as Trolox C ((?-6-hydroxy-2,5,7,8-tetramethylchromane-2carboxylic acid) and HPMC (6-hydroxy-2,2-5,7,8-pentamethylchroman) have been developed (Scheme 8; see references 133 and 134). As shown in Table 4, these three phenols show similar thermochemistry in the same solvent. This is in good agreement with their solution kinetic behavior and indicates that the analogs lacking the greasy phytyl tails are good models for the redox chemistry of tocopherol. The BDFEs of these phenols are much lower than those of other phenols, by more than 10 kcal mol-1 vs. unsubstituted phenol and by 2 kcal mol-1 vs. tBu3PhOH in the same solvent. This relatively weak bond is the origin of the good biological reducing power of vitamin E. The weak bond is a result of the electron-donating substituents, which also reduces the acidity of these phenols. The combination of a weak O bond, low acidity, and a high outer-sphere redox.

N by Tonks: Henry Ralph Lumley. Figure 4 shows Lumley before his

N by Tonks: Henry Ralph Lumley. Figure 4 shows Lumley before his injury. These photographs, like the other images reproduced in this article, can be found quite easily on the web, along with Lumley’s case notes, a series of photographs documenting the operations, and Tonks’ portrait.7 When I last checked, the pre-operative photograph had 254,405 hits, so either it has been seen by a considerable number of individuals, or there are people — like me — who’ve returned to it repeatedly, for whatever reason. Henry Lumley was admitted to the specialist hospital for facial casualties in October 1917. In his notes, Harold Gillies AnisomycinMedChemExpress Flagecidin describes Lumley’s condition on admission: the skin and subcutaneous tissue of his face had been destroyed by severe petrol burns, including the left eye and eyelid, both eyebrows, and the nose down to the cartilage. A Second Lieutenant in the Royal Flying Corps, Lumley had been wounded on 14 July 1916: by the time he came to Sidcup, he had lived with his injuries for over a year. No further mention is made of the accident in the case notes, but a genealogist working on Project Fa de looked up Lumley’s service records in The National Archives.8 A former operator with the Eastern Telegraph Company, Lumley was selected for the RFC’s Special Reserve of Officers in April 1916. He never made it out of England though: a letter from the Central Flying School in Upavon, dated 9 August 1916, reveals that the accident happened on the day of his graduation. The two operations at Sidcup, in November 1917 and February 1918, are documented in detail in the case notes, and revisited in Gillies’ 1920 textbook, Plastic Surgery of the Face, which is now out of copyright and freely available online.9 A diagram shows Gillies’ ambitious plan to remove the existing scar tissue and raise a large flap of skin from Lumley’s chest with pedicle tubes providing a further blood supply to the graft (Figure 5). Despite ongoing complications, the initial signs were encouraging, but by day three after the second operation the graft had developed gangrene. Henry Lumley died twenty-four days later on 11 March 1918. He was 26.P H OTO G R AP H I E SFIGURE 3 Photograph of patient before surgery, Lumley case file. Gillies Archives, Queen Mary’s Hospital Sidcup. Photograph courtesy of the Gillies Archives.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 4 Pre-injury photograph, Lumley case file. Gillies Archives, Queen Mary’s Hospital Sidcup. Photograph courtesy of the Gillies Archives.P H OTO G R AP H I E S(a)(b)FIGURE 5 Notes from Lumley case file. Reproduced with permission of the Gillies Archives, Queen Mary’s Hospital Sidcup.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EThe burdens of representationWhat do we gain from seeing images like these? What would constitute their proper — or improper — use? Susan Sontag’s book LumicitabineMedChemExpress ALS-8176 Regarding the Pain of Others is probably the most famous attempt to answer this question. In it she returns to the scene of her earlier study, On Photography, and reconsiders the claim, almost three decades on, that we (in the West) have become desensitised to the suffering of others; that this moral anaesthesia is directly attributable to the proliferation of images of appalling suffering. In On Photography Sontag pointed out an innate paradox of photographs: that they could, simultaneously, make an event more real than if one had never seen the photograph; but also — through “repeated exposure” -.N by Tonks: Henry Ralph Lumley. Figure 4 shows Lumley before his injury. These photographs, like the other images reproduced in this article, can be found quite easily on the web, along with Lumley’s case notes, a series of photographs documenting the operations, and Tonks’ portrait.7 When I last checked, the pre-operative photograph had 254,405 hits, so either it has been seen by a considerable number of individuals, or there are people — like me — who’ve returned to it repeatedly, for whatever reason. Henry Lumley was admitted to the specialist hospital for facial casualties in October 1917. In his notes, Harold Gillies describes Lumley’s condition on admission: the skin and subcutaneous tissue of his face had been destroyed by severe petrol burns, including the left eye and eyelid, both eyebrows, and the nose down to the cartilage. A Second Lieutenant in the Royal Flying Corps, Lumley had been wounded on 14 July 1916: by the time he came to Sidcup, he had lived with his injuries for over a year. No further mention is made of the accident in the case notes, but a genealogist working on Project Fa de looked up Lumley’s service records in The National Archives.8 A former operator with the Eastern Telegraph Company, Lumley was selected for the RFC’s Special Reserve of Officers in April 1916. He never made it out of England though: a letter from the Central Flying School in Upavon, dated 9 August 1916, reveals that the accident happened on the day of his graduation. The two operations at Sidcup, in November 1917 and February 1918, are documented in detail in the case notes, and revisited in Gillies’ 1920 textbook, Plastic Surgery of the Face, which is now out of copyright and freely available online.9 A diagram shows Gillies’ ambitious plan to remove the existing scar tissue and raise a large flap of skin from Lumley’s chest with pedicle tubes providing a further blood supply to the graft (Figure 5). Despite ongoing complications, the initial signs were encouraging, but by day three after the second operation the graft had developed gangrene. Henry Lumley died twenty-four days later on 11 March 1918. He was 26.P H OTO G R AP H I E SFIGURE 3 Photograph of patient before surgery, Lumley case file. Gillies Archives, Queen Mary’s Hospital Sidcup. Photograph courtesy of the Gillies Archives.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EFIGURE 4 Pre-injury photograph, Lumley case file. Gillies Archives, Queen Mary’s Hospital Sidcup. Photograph courtesy of the Gillies Archives.P H OTO G R AP H I E S(a)(b)FIGURE 5 Notes from Lumley case file. Reproduced with permission of the Gillies Archives, Queen Mary’s Hospital Sidcup.M E D I C A L A R C H I V E S A N D D I G I TA L C U L T U R EThe burdens of representationWhat do we gain from seeing images like these? What would constitute their proper — or improper — use? Susan Sontag’s book Regarding the Pain of Others is probably the most famous attempt to answer this question. In it she returns to the scene of her earlier study, On Photography, and reconsiders the claim, almost three decades on, that we (in the West) have become desensitised to the suffering of others; that this moral anaesthesia is directly attributable to the proliferation of images of appalling suffering. In On Photography Sontag pointed out an innate paradox of photographs: that they could, simultaneously, make an event more real than if one had never seen the photograph; but also — through “repeated exposure” -.

Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC

Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC, INBIO, INHS, NMNH). COSTA RICA, ACG database codes: See Appendix 2 for detailed label data. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: tegula pale, humeral complex half pale/half dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Fore wing length: 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.3?.5, rarely 2.0?.2. Interocellar distance/ posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.2?.3. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with punctures near margins, central part mostly smooth. Number of pits in scutoscutellar sulcus: 5 or 6 or 7 or 8. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.4?0.5. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: mostly sculptured. buy BEZ235 Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 2.8?.1. Mediotergite 2 sculpture: mostly smooth. Outer margin of hypopygium: with a wide, medially folded,Review of Apanteles sensu stricto (Hymenoptera, Braconidae, Microgastrinae)…transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.6?.7, rarely 1.2?.3. Length of fore wing veins r/2RS: 1.7?.9. Length of fore wing veins 2RS/2M: 0.9?.0. Length of fore wing veins 2M/(RS+M)b: 0.9?.0. Pterostigma length/width: 3.6 or more. Point of insertion of vein r in pterostigma: order PP58 clearly beyond half way point length of pterostigma. Angle of vein r with fore wing anterior margin: clearly outwards, inclined towards fore wing apex. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. As in female but with darker legs and smoother mediotergite 1. Molecular data. Sequences in BOLD:.Tobal, Rio Blanco Abajo, 04.iv.2002, 500m, 10.90037, -85.37254, DHJPAR0002960. Paratypes. 40 , 6 (BMNH, CNC, INBIO, INHS, NMNH). COSTA RICA, ACG database codes: See Appendix 2 for detailed label data. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso, metacoxa): dark, dark, dark. Femora color (pro-, meso-, metafemur): anteriorly dark/ posteriorly pale, dark, dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: tegula pale, humeral complex half pale/half dark. Pterostigma color: mostly pale and/or transparent, with thin dark borders. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Fore wing length: 2.9?.0 mm, 3.1?.2 mm, rarely 2.0 mm or less or 3.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.3?.5, rarely 2.0?.2. Interocellar distance/ posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 2.0?.2. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.2?.3. Metatibia inner spur length/metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with punctures near margins, central part mostly smooth. Number of pits in scutoscutellar sulcus: 5 or 6 or 7 or 8. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.4?0.5. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: mostly sculptured. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 2.8?.1. Mediotergite 2 sculpture: mostly smooth. Outer margin of hypopygium: with a wide, medially folded,Review of Apanteles sensu stricto (Hymenoptera, Braconidae, Microgastrinae)…transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.6?.7, rarely 1.2?.3. Length of fore wing veins r/2RS: 1.7?.9. Length of fore wing veins 2RS/2M: 0.9?.0. Length of fore wing veins 2M/(RS+M)b: 0.9?.0. Pterostigma length/width: 3.6 or more. Point of insertion of vein r in pterostigma: clearly beyond half way point length of pterostigma. Angle of vein r with fore wing anterior margin: clearly outwards, inclined towards fore wing apex. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. As in female but with darker legs and smoother mediotergite 1. Molecular data. Sequences in BOLD:.

With similar connectivity profiles. We have shown how both global digital

With similar connectivity profiles. We have shown how both global digital and physical network flows can contribute to support a better monitoring of SDG indicators, as illustrated by the high correlation between Internet and postal flows on the one hand, with an exhaustive list of socioeconomic indicators on the other hand.PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,16 /The International Postal Network and Other Global Flows as Nutlin (3a) web proxies for National WellbeingWe also note the considerable potential, exposed here, for future applications of postal flow data. While we have here restricted our analysis to country-level relations, postal flows allow for socio-economic mapping on a sub-national level which can inform development programmes on a practical level. An additional dimension to be explored–that is beyond the scope of this paper is temporal analysis which, combined with the multiplex network model presented above, could provide early warning of economic shocks and their propagation [41]. Interestingly, despite the ease of digital interactions and subsequent evidence that `distance is dead’ [42], physical networks, particularly the global postal, flight and migration networks, are still stronger candidates for proxy variables in case of missing data than digital networks such as the Internet or social media. These networks not only reach populations excluded from access to digital communications, but are also associated with the highest RDX5791 solubility number of country pairs sharing relatively similar socioeconomic patterns, in turn opening numerous ways of completing missing data with proxy variables. In the digital era, greater granularity and frequency of analysis and monitoring of SDGs can, paradoxically, be achieved through global physical networks data. We expect that the value as proxies for the digital communication networks will increase as they mature, expand and become more accessible. In the near future, both physical and digital networks will need to be combined to optimise monitoring efforts. In that sense, the emergence of the Internet of things (IoT) could play a critical role by making even more fuzzy the frontiers between the digital and physical worlds.Supporting InformationS1 Fig. Correlation matrix augmented with correlation coefficients for each cell. All results are statistically significant with p<0.05. (EPS) S1 Table. Two-sample Kolmogorov-Smirnov test statistic results and p-values for socioeconomic indicator differences between pairs of countries with minimal and maximal community multiplexity values (1 and 6). (TEX) S1 File. International postal network edges, where Source is the sending country, Target is the receiving country and Weight is the volume of post sent, normalised over the Source country population and scaled. (CSV)AcknowledgmentsDesislava Hristova was supported by the Project LASAGNE, Contract No. 318132 (STREP), funded by the European Commission and EPSRC through Grant GALE (EP/K019392). We are grateful to Andrei Bejan for the statistics consultation and Noa Zilberman for advice on the DIMES Project data.Author ContributionsConceived and designed the experiments: DH AR JA MLO. Performed the experiments: DH. Analyzed the data: DH AR JA. Contributed reagents/materials/analysis tools: AR JA MLO. Wrote the paper: DH AR JA MLO CM.
Integrated Care Settings (ICS) provide a holistic approach to the transition from chronic kidney disease into renal replacement therapy (RRT), offering at least both types of d.With similar connectivity profiles. We have shown how both global digital and physical network flows can contribute to support a better monitoring of SDG indicators, as illustrated by the high correlation between Internet and postal flows on the one hand, with an exhaustive list of socioeconomic indicators on the other hand.PLOS ONE | DOI:10.1371/journal.pone.0155976 June 1,16 /The International Postal Network and Other Global Flows as Proxies for National WellbeingWe also note the considerable potential, exposed here, for future applications of postal flow data. While we have here restricted our analysis to country-level relations, postal flows allow for socio-economic mapping on a sub-national level which can inform development programmes on a practical level. An additional dimension to be explored–that is beyond the scope of this paper is temporal analysis which, combined with the multiplex network model presented above, could provide early warning of economic shocks and their propagation [41]. Interestingly, despite the ease of digital interactions and subsequent evidence that `distance is dead’ [42], physical networks, particularly the global postal, flight and migration networks, are still stronger candidates for proxy variables in case of missing data than digital networks such as the Internet or social media. These networks not only reach populations excluded from access to digital communications, but are also associated with the highest number of country pairs sharing relatively similar socioeconomic patterns, in turn opening numerous ways of completing missing data with proxy variables. In the digital era, greater granularity and frequency of analysis and monitoring of SDGs can, paradoxically, be achieved through global physical networks data. We expect that the value as proxies for the digital communication networks will increase as they mature, expand and become more accessible. In the near future, both physical and digital networks will need to be combined to optimise monitoring efforts. In that sense, the emergence of the Internet of things (IoT) could play a critical role by making even more fuzzy the frontiers between the digital and physical worlds.Supporting InformationS1 Fig. Correlation matrix augmented with correlation coefficients for each cell. All results are statistically significant with p<0.05. (EPS) S1 Table. Two-sample Kolmogorov-Smirnov test statistic results and p-values for socioeconomic indicator differences between pairs of countries with minimal and maximal community multiplexity values (1 and 6). (TEX) S1 File. International postal network edges, where Source is the sending country, Target is the receiving country and Weight is the volume of post sent, normalised over the Source country population and scaled. (CSV)AcknowledgmentsDesislava Hristova was supported by the Project LASAGNE, Contract No. 318132 (STREP), funded by the European Commission and EPSRC through Grant GALE (EP/K019392). We are grateful to Andrei Bejan for the statistics consultation and Noa Zilberman for advice on the DIMES Project data.Author ContributionsConceived and designed the experiments: DH AR JA MLO. Performed the experiments: DH. Analyzed the data: DH AR JA. Contributed reagents/materials/analysis tools: AR JA MLO. Wrote the paper: DH AR JA MLO CM.
Integrated Care Settings (ICS) provide a holistic approach to the transition from chronic kidney disease into renal replacement therapy (RRT), offering at least both types of d.

L abuse in males (Tables 4 and S2 Table) and an association

L abuse in males (Tables 4 and S2 Table) and an association among females disappeared with adjustment for physical abuse (S3 Table). In females but not males buy TSA faster zBMI gains with age were observed for ICG-001 web sexual abuse, by 0.0034/y, although confidence intervals include 0. For obesity, sexual abuse was associated with a lower ORadjusted at 7y of 0.23 (0.06,0.84) but faster, 1.04 (1.01,1.08) fold/y, linear increase with age such that the ORadjusted increased to 0.44 at 23y, to 1.09 at 45yPLOS ONE | DOI:10.1371/journal.pone.0119985 March 26,8 /Child Maltreatment and BMI TrajectoriesTable 4. Mean differences in zBMI (95 CIs) at 7y and rate of change in zBMI (7?0y) by childhood maltreatment, estimated using multilevel models.Mean difference in 7y z-BMI or rate of zBMI change Males Physical abuse 7y z-BMI rate of change in z-BMI Psychological abuse 7y z-BMI rate of change in z-BMI Sexual abuse 7y z-BMI rate of change in z-BMI Neglect 7 and/or 11 7y z-BMI coefficient for interaction with age coefficient for interaction with age2 Females Physical abuse 7y z-BMI rate of change in z-BMI Psychological abuse 7y z-BMI rate of change in z-BMI Sexual abuse 7y z-BMI rate of change in z-BMI Neglect 7 and/or 11 7y z-BMI coefficient for interaction with age coefficient for interaction with age2 0.0039 (-0.0527,0.0605) 0.0131 (0.0087,0.0174) -0.0002 (-0.0003,-0.0001) -0.0728 (-0.1300,-0.0157) 0.0130 (0.0086,0.0173) -0.0002 (-0.0003,-0.0001) -0.0634 (-0.1223,-0.0045) 0.0129 (0.0086,0.0173) -0.0002 (-0.0003,-0.0001) -0.0622 (-0.1211,-0.0032) 0.0127 (0.0083,0.0170) -0.0002 (-0.0003,-0.0001) -0.0601 (-0.2230,0.1027) 0.0034 (-0.0014,0.0082) -0.0651 (-0.2238,0.0935) 0.0033 (-0.0015,0.0081) -0.0790 (-0.2367,0.0787) 0.0036 (-0.0012,0.0084) -0.0795 (-0.2371,0.0782) 0.0034 (-0.0014,0.0082) -0.0762 (-0.1576,0.0051) 0.0035 (0.0011,0.0059) -0.0926 (-0.1711,-0.0142) 0.0035 (0.0011,0.0059) -0.0593 (-0.1368,0.0182) 0.0036 (0.0013,0.0060) -0.0592 (-0.1368,0.0183) 0.0035 (0.0011,0.0059) -0.0876 (-0.1964,0.0212) 0.0066 (0.0034,0.0098) -0.1132 (-0.2180,-0.0083) 0.0066 (0.0034,0.0098) -0.0971 (-0.2005,0.0064) 0.0068 (0.0036,0.0100) -0.0969 (-0.2004,0.0066) 0.0066 (0.0034,0.0098) -0.0883 (-0.1425,-0.0340) 0.0156 (0.0109,0.0203) -0.0003 (-0.0004,-0.0002) -0.1488 (-0.2010,-0.0967) 0.0156 (0.0108,0.0204) -0.0003 (-0.0004,-0.0002) -0.1612 (-0.2147,-0.1078) 0.0167 (0.0120,0.0215) -0.0003 (-0.0004,-0.0002) -0.1605 (-0.2140,-0.1070) 0.0166 (0.0118,0.0213) -0.0003 (-0.0004,-0.0002) 0.2089 (-0.1611,0.5789) -0.0017 (-0.0128,0.0093) 0.0995 (-0.2554,0.4544) -0.0016 (-0.0127,0.0094) 0.0799 (-0.2742,0.4340) -0.0007 (-0.0118,0.0103) 0.0804 (-0.2736,0.4345) -0.0009 (-0.0119,0.0101) 0.0201 (-0.0728,0.1131) 0.0011 (-0.0016,0.0039) 0.0231 (-0.0660,0.1122) 0.0011 (-0.0016,0.0039) 0.0201 (-0.0684,0.1086) 0.0015 (-0.0012,0.0043) 0.0203 (-0.0681,0.1088) 0.0014 (-0.0013,0.0042) -0.0503 (-0.1588,0.0583) 0.0052 (0.0020,0.0085) -0.0767 (-0.1805,0.0271) 0.0052 (0.0020,0.0084) -0.0737 (-0.1774,0.0300) 0.0057 (0.0025,0.0089) -0.0735 (-0.1772,0.0302) 0.0057 (0.0024,0.0089) Unadjusted Adjusted (A)* Adjusted (A+B)** Adjusted (A+B+C)***Mean difference in rate of change (i.e. additional rate of change associated with maltreatment) is represented by the coefficient for a linear age interaction term (and for 7y/11y neglect only it is a linear function of age: i.e. coefficient for interaction with age +2*(coefficient for interaction with age2)* age (where age is centred at 7y) *A: adjusted for: social class at birt.L abuse in males (Tables 4 and S2 Table) and an association among females disappeared with adjustment for physical abuse (S3 Table). In females but not males faster zBMI gains with age were observed for sexual abuse, by 0.0034/y, although confidence intervals include 0. For obesity, sexual abuse was associated with a lower ORadjusted at 7y of 0.23 (0.06,0.84) but faster, 1.04 (1.01,1.08) fold/y, linear increase with age such that the ORadjusted increased to 0.44 at 23y, to 1.09 at 45yPLOS ONE | DOI:10.1371/journal.pone.0119985 March 26,8 /Child Maltreatment and BMI TrajectoriesTable 4. Mean differences in zBMI (95 CIs) at 7y and rate of change in zBMI (7?0y) by childhood maltreatment, estimated using multilevel models.Mean difference in 7y z-BMI or rate of zBMI change Males Physical abuse 7y z-BMI rate of change in z-BMI Psychological abuse 7y z-BMI rate of change in z-BMI Sexual abuse 7y z-BMI rate of change in z-BMI Neglect 7 and/or 11 7y z-BMI coefficient for interaction with age coefficient for interaction with age2 Females Physical abuse 7y z-BMI rate of change in z-BMI Psychological abuse 7y z-BMI rate of change in z-BMI Sexual abuse 7y z-BMI rate of change in z-BMI Neglect 7 and/or 11 7y z-BMI coefficient for interaction with age coefficient for interaction with age2 0.0039 (-0.0527,0.0605) 0.0131 (0.0087,0.0174) -0.0002 (-0.0003,-0.0001) -0.0728 (-0.1300,-0.0157) 0.0130 (0.0086,0.0173) -0.0002 (-0.0003,-0.0001) -0.0634 (-0.1223,-0.0045) 0.0129 (0.0086,0.0173) -0.0002 (-0.0003,-0.0001) -0.0622 (-0.1211,-0.0032) 0.0127 (0.0083,0.0170) -0.0002 (-0.0003,-0.0001) -0.0601 (-0.2230,0.1027) 0.0034 (-0.0014,0.0082) -0.0651 (-0.2238,0.0935) 0.0033 (-0.0015,0.0081) -0.0790 (-0.2367,0.0787) 0.0036 (-0.0012,0.0084) -0.0795 (-0.2371,0.0782) 0.0034 (-0.0014,0.0082) -0.0762 (-0.1576,0.0051) 0.0035 (0.0011,0.0059) -0.0926 (-0.1711,-0.0142) 0.0035 (0.0011,0.0059) -0.0593 (-0.1368,0.0182) 0.0036 (0.0013,0.0060) -0.0592 (-0.1368,0.0183) 0.0035 (0.0011,0.0059) -0.0876 (-0.1964,0.0212) 0.0066 (0.0034,0.0098) -0.1132 (-0.2180,-0.0083) 0.0066 (0.0034,0.0098) -0.0971 (-0.2005,0.0064) 0.0068 (0.0036,0.0100) -0.0969 (-0.2004,0.0066) 0.0066 (0.0034,0.0098) -0.0883 (-0.1425,-0.0340) 0.0156 (0.0109,0.0203) -0.0003 (-0.0004,-0.0002) -0.1488 (-0.2010,-0.0967) 0.0156 (0.0108,0.0204) -0.0003 (-0.0004,-0.0002) -0.1612 (-0.2147,-0.1078) 0.0167 (0.0120,0.0215) -0.0003 (-0.0004,-0.0002) -0.1605 (-0.2140,-0.1070) 0.0166 (0.0118,0.0213) -0.0003 (-0.0004,-0.0002) 0.2089 (-0.1611,0.5789) -0.0017 (-0.0128,0.0093) 0.0995 (-0.2554,0.4544) -0.0016 (-0.0127,0.0094) 0.0799 (-0.2742,0.4340) -0.0007 (-0.0118,0.0103) 0.0804 (-0.2736,0.4345) -0.0009 (-0.0119,0.0101) 0.0201 (-0.0728,0.1131) 0.0011 (-0.0016,0.0039) 0.0231 (-0.0660,0.1122) 0.0011 (-0.0016,0.0039) 0.0201 (-0.0684,0.1086) 0.0015 (-0.0012,0.0043) 0.0203 (-0.0681,0.1088) 0.0014 (-0.0013,0.0042) -0.0503 (-0.1588,0.0583) 0.0052 (0.0020,0.0085) -0.0767 (-0.1805,0.0271) 0.0052 (0.0020,0.0084) -0.0737 (-0.1774,0.0300) 0.0057 (0.0025,0.0089) -0.0735 (-0.1772,0.0302) 0.0057 (0.0024,0.0089) Unadjusted Adjusted (A)* Adjusted (A+B)** Adjusted (A+B+C)***Mean difference in rate of change (i.e. additional rate of change associated with maltreatment) is represented by the coefficient for a linear age interaction term (and for 7y/11y neglect only it is a linear function of age: i.e. coefficient for interaction with age +2*(coefficient for interaction with age2)* age (where age is centred at 7y) *A: adjusted for: social class at birt.

A six-min incubation with Gentle Cell Dissociation Reagent followed by complete

A six-min incubation with Gentle Cell Dissociation Reagent followed by complete physical dispersions by repeated pipetting. Large cells (>70 m) were then collected by passing the suspension successively buy GW 4064 through a series of nylon cell GW 4064 solubility strainers (70 m and 40 m, Fisher Scientific) to generate three cell size fractions (>70 m, 40?0 m, and <40 m). The captured cells on the strainer were recovered by inverting the strainer and rinsing with culture medium. Similarly, middle size cells (40?0 m) were obtained from the <70-m fraction by collection on a 40-m cell strainer after removal of <70-m cells. The three size fractions were used in all subsequent analyses. Portions of the size-fractioned cells were fixed in 4 (vol/vol) paraformaldehyde/PBS solution for 15 min and resuspended (5.0 ?102 and 1.0 ?105 cells/100 L PBS). The suspensions were loaded into a Shandon single cytofunnel and centrifuged for 5 min at 1,000 ?g in a Shandon CytoSpin 4 cytocentrifuge (Thermo Scientific). Derivation Primary Human PHTu and PHTd. Placental tissue samples were collected by the Obstetrical Specimen Procurement Unit at Magee-Womens Hospital of the University of Pittsburgh Medical Center. The work was performed under an exempt protocol approved by the Institutional Review Board (IRB) at the University of Pittsburgh. Under the protocol, patients provided written consent for the use of deidentified discarded tissues for research upon admittance to the hospital. Primary villous PHTs were derived and cultured according to published procedures (12, 49, 50) from three term human placentas (one female and two males). Multiple primary cultures were established from each placenta at a density of 3.5 ?105 cells/cm2 in DMEM supplemented with 10 (vol/vol) FBS and antibiotics under a 5 (vol/vol) CO2/air atmosphere at 37 . Triplicate cultures from each placenta were harvested at 9 h (PHTu) before syncytium formation and subsequently at 48 h (PHTd) when syncytium formation had occurred. The sieving technique used for the hESC-derived cells was thus unnecessary for the term placental STB. Total RNA was extracted from each sample (3 ?3 at 9 h and 48 h, respectively) to provide a total of 18 samples for RNA-seq analysis. Additional methods are described in SI Appendix, SI Materials and Methods. ACKNOWLEDGMENTS. We thank L. C. Schulz for her critical reading of the manuscript and her helpful comments; N. J. Bivens for RNA-seq; W. Spollen, C. Bottoms, and S. Givan for their sequence data analysis; Y. Tian for immunoassays; A. Jurkevich for technical assistance; M. Schauflinger, D. Grant, and T. A. White for sharing equipment; and D. F. Reith for his editorial assistance and administrative support. This study was supported by NIH Grant R01HD077108 (to T.E. and D.J.S.) and Grant R01HD067759 (to R.M.R.).7. Loke YW, King A (1995) Human Implantation: Cell Biology and Immunology (Cambridge Univ Press, Cambridge). 8. Miller RK, et al. (2005) Human placental explants in culture: Approaches and assessments. Placenta 26(6):439?48. 9. Sim CM, Sibley CP, Jones CJ, Turner MA, Greenwood SL (2001) The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am J Physiol Regul Integr Comp Physiol 280(4):R1116 1122. 10. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186(2):306?16. 11. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B (2010) The choriocarcinoma cell line BeW.A six-min incubation with Gentle Cell Dissociation Reagent followed by complete physical dispersions by repeated pipetting. Large cells (>70 m) were then collected by passing the suspension successively through a series of nylon cell strainers (70 m and 40 m, Fisher Scientific) to generate three cell size fractions (>70 m, 40?0 m, and <40 m). The captured cells on the strainer were recovered by inverting the strainer and rinsing with culture medium. Similarly, middle size cells (40?0 m) were obtained from the <70-m fraction by collection on a 40-m cell strainer after removal of <70-m cells. The three size fractions were used in all subsequent analyses. Portions of the size-fractioned cells were fixed in 4 (vol/vol) paraformaldehyde/PBS solution for 15 min and resuspended (5.0 ?102 and 1.0 ?105 cells/100 L PBS). The suspensions were loaded into a Shandon single cytofunnel and centrifuged for 5 min at 1,000 ?g in a Shandon CytoSpin 4 cytocentrifuge (Thermo Scientific). Derivation Primary Human PHTu and PHTd. Placental tissue samples were collected by the Obstetrical Specimen Procurement Unit at Magee-Womens Hospital of the University of Pittsburgh Medical Center. The work was performed under an exempt protocol approved by the Institutional Review Board (IRB) at the University of Pittsburgh. Under the protocol, patients provided written consent for the use of deidentified discarded tissues for research upon admittance to the hospital. Primary villous PHTs were derived and cultured according to published procedures (12, 49, 50) from three term human placentas (one female and two males). Multiple primary cultures were established from each placenta at a density of 3.5 ?105 cells/cm2 in DMEM supplemented with 10 (vol/vol) FBS and antibiotics under a 5 (vol/vol) CO2/air atmosphere at 37 . Triplicate cultures from each placenta were harvested at 9 h (PHTu) before syncytium formation and subsequently at 48 h (PHTd) when syncytium formation had occurred. The sieving technique used for the hESC-derived cells was thus unnecessary for the term placental STB. Total RNA was extracted from each sample (3 ?3 at 9 h and 48 h, respectively) to provide a total of 18 samples for RNA-seq analysis. Additional methods are described in SI Appendix, SI Materials and Methods. ACKNOWLEDGMENTS. We thank L. C. Schulz for her critical reading of the manuscript and her helpful comments; N. J. Bivens for RNA-seq; W. Spollen, C. Bottoms, and S. Givan for their sequence data analysis; Y. Tian for immunoassays; A. Jurkevich for technical assistance; M. Schauflinger, D. Grant, and T. A. White for sharing equipment; and D. F. Reith for his editorial assistance and administrative support. This study was supported by NIH Grant R01HD077108 (to T.E. and D.J.S.) and Grant R01HD067759 (to R.M.R.).7. Loke YW, King A (1995) Human Implantation: Cell Biology and Immunology (Cambridge Univ Press, Cambridge). 8. Miller RK, et al. (2005) Human placental explants in culture: Approaches and assessments. Placenta 26(6):439?48. 9. Sim CM, Sibley CP, Jones CJ, Turner MA, Greenwood SL (2001) The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am J Physiol Regul Integr Comp Physiol 280(4):R1116 1122. 10. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186(2):306?16. 11. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B (2010) The choriocarcinoma cell line BeW.

‘ coordinate is the percentage of roles (s)he accepted for each

‘ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in Tyrphostin AG 490 web abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect Necrostatin-1 price againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.’ coordinate is the percentage of roles (s)he accepted for each category. Scatterplots are for (a) ordinary favorable roles, (b) extraordinary favorable roles, (c) ordinary unfavorable roles, and (d) extraordinary unfavorable roles. SPQ, schizotypal personality questionnaire.** ** * ** * ** **Reaction Times (ms)Percentage of accepted roles70 60 50 40 30 20 101180 1160 1140 1120 1100 1080 1060 1040 1020 1000 980 960 940 920**Ordinary FavorableOrdinary Extraordinary Unfavorable Favorable Category combinations High SPQ scorersExtraordinary UnfavorableOrdinary FavorableExtraordinary Ordinary Favorable Unfavorable Category combinations High extraordinary role acceptersExtraordinary UnfavorableLow SPQ scorersLow extraordinary role acceptersAcceptanceRejectionFigure 2. Percentages of social roles accepted in each category for high- and low-SPQ scorers and standard errors (vertical bars) for the 203 participants. *P o0.05, **P o0.0001. SPQ, schizotypal personality questionnaire.Figure 3. Mean reaction times and standard errors (vertical bars) for accepted (plain rectangles) and rejected (crosshatched rectangles) social roles for high and low extraordinary roles accepters. *Po 0.05.(i.e., bizarre behavior, thought disorders, unusual thoughts, poor insight, and difficulty in abstract thinking).16 In accordance with that view, the multiple regression suggested that the tendency to accept ordinary favorable roles had some protective effect againstnpj Schizophrenia (2016)schizotypal traits. Across all the categories, individuals with higher SPQ scores accepted more social roles than those with lower scores. All these results are reminiscent of the numerous anecdotes, so often published in the media, about thePublished in partnership with the Schizophrenia International Research SocietyExtraordinary roles and schizotypy AL Fernandez-Cruz et al5 disorganization of famous artists and the extraordinary roles they perform in society, now and in the past.17 On the other hand, works, such as the study of Twomey et al.,18 link psychoticism to openness to experience, sensation-seeking and creativity. Similarly, it was observed that, among writers and actors, scores for psychoticism were higher than among less `creative’ individuals19 and Andreasen noted in 1996 (ref. 20) that highly creative people had higher scores on measures of psychopathology than less creative people. In our case, this is akin to individuals who accept a lesser percentage of extraordinary social roles having lower SPQ scores. Further supporting the drive hypothesis, high accepters of extraordinary roles appeared `more enthusiast’ at accepting roles and more reluctant at rejecting them as they took less times for acceptances and more times for rejections than low accepters. This could be related to a higher baseline level of activation of the brain representations of these roles in the participants with higher SPQ scores. These results were obtained in a sample of the general population. Given the low frequency of schizotypy and of schizophrenia in that population, it is highly unlikely that those who accepted more extraordinary roles did it as a consequence of some pre-existing schizophrenia factors. One could eliminate an effect of the cognitive deficits found in the continuum going from normality to schizophrenia via schizotypy.9?3,21 In the task, these deficits would have induced longer reaction times for those who accepted more extraordinary roles or for the subgroup with higher SPQ.

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting

D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent OPC-8212 supplier drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolescent’s social goals, and grade. Social Norms According to the Focus Theory of Normative Conduct, individuals adjust their behavior to match that of a relevant referent group because norms dictate what behaviors are socially acceptable (Cialdini and Goldstein, 2004). In this regard, social norms have been conceptualized as informal rules and standards that groups adopt to guide and constrain behavior (Cialdini and Trost, 1998). The SB856553 msds evidence suggests that two types of perceived social norms are particularly relevant for understanding adolescent drinking behaviors, descriptive norms (perceptions of peer drinking) and injunctive norms (perceptions of the acceptability of peer drinking) (Borsari and Carey, 2001). Descriptive and injunctive norms have been associated with a variety of drinking behaviors in both cross-sectional and longitudinal studies (Collins and Spelman, 2013 Larimer et al., 2004; Read et al., 2002; Teunissen et al.D ETS-1 blockade have beneficial additive effects on renal injury, suggesting that concomitant blockade of RAS and ETS-1 could be a novel therapeutic strategy for the treatment and prevention of end-organ injury in hypertension.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAcknowledgmentsWe are grateful for the support of Core Facilities at the O’Brien Kidney Center at the University of Alabama at Birmingham. Sources of Funding A Merit Review Award (E.A. Jaimes), a Research Grant (1 IP1 BX001595; P.W. Sanders and E.A. Jaimes) from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, a National Institute of Diabetes and Digestive and Kidney Diseases George M. O’Brien Kidney and Urological Research Centers Program Grant P30-DK-079337, and a Byrne Fund Grant (E.A. Jaimes) from Memorial Sloan Kettering Cancer Center funded these studies.
Adolescence is the developmental period most strongly associated with the initiation and escalation of substance use (Colder et al., 2002). Adolescent alcohol use is of concern because it is often associated with a variety of negative consequences including increased alcohol use later in life (Hawkins et al., 1997), decreased academic performance (Balsa et al., 2011), and illicit drug use (Hill et al., 2000). Understanding the factors that influence adolescent drinking is important for developing empirically supported etiological models and effective interventions. During adolescence, an increasing amount of time is spent outside of the home and in the context of peers (Spear, 2000), and peers are believed to play a central role in the initiation and escalation of adolescent alcohol use (Barnes et al., 2007). Adolescents are often motivated to align their behaviors and opinions with those of their peers in part because they have a strong desire to maintain close peer relationships and to be accepted by their peers groups (Collins and Steinberg, 2006). Thus, perceived peer norms (e.g., perceptions of the behaviors peers engage in as well as perceptions of behaviors peers approve of) are viewed as an important mechanism through which peers influence a variety of behaviors, including alcohol use (Borsari and Carey, 2001; Cialdini and Goldstein, 2004). In this study, we propose that the influence of perceived norms on adolescent early alcohol use is not uniform and test whether the strength of the association between perceived norms and alcohol use depends on the type of social norm (descriptive or injunctive), an adolesce