100 research outputs found
\u3cem\u3eCatena\u3c/em\u3e-Poly[[Bis(α-Thenoyltrifluoroacetonato)Copper(II)]-μ-1,4-Di-4-Pyridyl-2,3-Diazabuta-1,3-Diene]
In the one-dimensional title polymer, [Cu(C8H4F3O2S)2(C12H10N4)]n or [Cu(L)2(tta)2] [tta is -thenoyltrifluoroacetonato and L is 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene], Cu2+ lies on a center of inversion. It is axially coordinated by two pyridyl N atoms from two different L ligands and equatorially coordinated by four O atoms from two chelating tta ligands. The ligand L propagates the one-dimensional chain structure by serving as a bridging ligand between two Cu octahedra via Cu-N coordinate bonds
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Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy
We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated
Matriz swot como ferramenta de gestão para melhoria da assistência de enfermagem:: estudo de caso em um hospital de ensino
Este trabalho apresenta um estudo de caso de aplicação da Matriz SWOT no planejamento da assistência de enfermagem de uma Clínica Médica do Hospital Universitário Clemente de Faria (HUCF), em Montes Claros ”“ Minas Gerais. Trata-se de estudo qualitativo e descritivo, cuja coleta de dados foi realizada no segundo semestre de 2012, por meio de observações dos processos de trabalho no setor, análise de processos administrativos e exame de rotinas do serviço. Para o diagnóstico do setor, utilizou-se a Matriz SWOT (Strengths, Weaknesses, Opportunities and Threats), pela qual foram analisadas as condições internas e externas. Utilizou-se de um processo interativo para análise das Fortalezas, Oportunidades, Fraquezas e Ameaças, com as seguintes finalidades: analisar e melhor utilizar os pontos fortes; eliminar os pontos fracos; conhecer e usufruir as oportunidades externas e, evitar as ameaças. Após a coleta, definido os pontos e realizado a análise SWOT, traçou-se os planos para melhoria da assistência de enfermagem. Conclui-se que a ferramenta SWOT proporcionou a clínica o conhecimento das fragilidades e potencialidades, a fim de equilibrar e melhorar a qualidade da assistência de enfermagem
Targeting the Lactate Transporter MCT1 in Endothelial Cells Inhibits Lactate-Induced HIF-1 Activation and Tumor Angiogenesis
Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1) pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs) thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1) that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2) and basic fibroblast growth factor (bFGF) expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
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