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191.
Elham Zarrinpashneh Tommaso Poggioli Padmini Sarathchandra Jonas Lexow Laurent Monassier Cesare Terracciano Florian Lang Federico Damilano Jessica Q. Zhou Anthony Rosenzweig Nadia Rosenthal Maria Paola Santini 《PloS one》2013,8(11)
Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-κB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo. 相似文献
192.
Jelena M Kezic Tibor T Glant James T Rosenbaum Holly L Rosenzweig 《Arthritis research & therapy》2012,14(1):R18-9
Introduction
Uveitis, or intraocular inflammatory disease, is a frequent extra-articular manifestation of several forms of arthritis. Despite the frequent co-occurrence of uveitis and arthritis, little is understood of the eye's predisposition to this disease. We recently described a previously unreported uveitis in a murine model of spondyloarthropathy triggered by autoimmunity to aggrecan, a prominent proteoglycan (PG) macromolecule in cartilage. In contrast to the joint and spine, wherein interferon-gamma (IFNγ) deficiency reduced disease, IFNγ deficiency worsened uveitis. Given the regulatory role of IFNγ on the Th17 response and the current focus of anti-interleukin-17 therapeutics in patients with uveitis and spondyloarthritis, we sought to determine the extent to which interleukin (IL)-17 mediates uveitis in the absence of IFNγ. 相似文献193.
Rodney Rouse Leshuai Zhang Katherine Shea Hongfei Zhou Lin Xu Sharron Stewart Barry Rosenzweig Jun Zhang 《PloS one》2014,9(10)
This study expanded upon a previous study in mice reporting a link between exenatide treatment and exocrine pancreatic injury by demonstrating temporal and dose responses and providing an initial mechanistic hypothesis. The design of the present study included varying lengths of exenatide exposure (3, 6 weeks to 12 weeks) at multiple concentrations (3, 10, or 30 µg/kg) with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles). Time- and dose-dependent exocrine pancreatic injury was observed in mice on a high fat diet treated with exenatide. The morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy), cell adaptations (hypertrophy and hyperplasia), and cell survival (proliferation/regeneration) accompanied by varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles indicated increased signaling for cell survival and altered lipid metabolism in exenatide treated mice. Immunohistochemistry supported gene expression findings that exenatide caused and/or exacerbated pancreatic injury in a high fat diet environment potentially by further increasing high fat diet exacerbated lipid metabolism and resulting oxidative stress. Further investigation is required to confirm these findings and determine their relevance to human disease. 相似文献
194.
TrpA1 regulates thermal nociception in Drosophila 总被引:1,自引:0,他引:1
Neely GG Keene AC Duchek P Chang EC Wang QP Aksoy YA Rosenzweig M Costigan M Woolf CJ Garrity PA Penninger JM 《PloS one》2011,6(8):e24343
Pain is a significant medical concern and represents a major unmet clinical need. The ability to perceive and react to tissue-damaging stimuli is essential in order to maintain bodily integrity in the face of environmental danger. To prevent damage the systems that detect noxious stimuli are therefore under strict evolutionary pressure. We developed a high-throughput behavioral method to identify genes contributing to thermal nociception in the fruit fly and have reported a large-scale screen that identified the Ca2+ channel straightjacket (stj) as a conserved regulator of thermal nociception. Here we present the minimal anatomical and neuronal requirements for Drosophila to avoid noxious heat in our novel behavioral paradigm. Bioinformatics analysis of our whole genome data set revealed 23 genes implicated in Ca2+ signaling that are required for noxious heat avoidance. One of these genes, the conserved thermoreceptor TrpA1, was confirmed as a bona fide “pain” gene in both adult and larval fly nociception paradigms. The nociceptive function of TrpA1 required expression within the Drosophila nervous system, specifically within nociceptive multi-dendritic (MD) sensory neurons. Therefore, our analysis identifies the channel TRPA1 as a conserved regulator of nociception. 相似文献
195.
甲亢患者甲状腺激素水平与血脂代谢相关性分析及临床意义探讨 总被引:1,自引:0,他引:1
目的:探讨甲亢患者甲状腺激素水平与血脂代谢指标之间的关系。方法:对160例甲亢患者治疗前后的甲状腺激素(TH)水平、血脂水平进行对照分析。结果:甲亢治疗前后与健康对照组比较,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)明显增高,促甲状腺激素(TSH)明显降低,差异有统计学意义(P<0.01);总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(apoAΙ)、载脂蛋白B(apoB)均明显降低,且差异具有统计学意义(P<0.01);低密度脂蛋白胆固醇(HDL-C)无明显变化(P>0.05)。结论:甲状腺激素与脂类代谢密切相关,临床上在诊治甲亢患者时,应当加强血脂水平的监测,以便更好地指导临床诊治,为疾病的发生发展、判断预后提供有价值的实验室检测指标。 相似文献
196.
The ammonia monooxygenase (AMO)/particulate methane monooxygenase (pMMO) superfamily is a diverse group of membrane‐bound enzymes of which only pMMO has been characterized on the molecular level. The pMMO active site is believed to reside in the soluble N‐terminal region of the pmoB subunit. To understand the degree of structural conservation within this superfamily, the crystal structure of the corresponding domain of an archaeal amoB subunit from Nitrosocaldus yellowstonii has been determined to 1.8 Å resolution. The structure reveals a remarkable conservation of overall fold and copper binding site location as well as several notable differences that may have implications for function and stability. Proteins 2014; 82:2263–2267. © 2014 Wiley Periodicals, Inc. 相似文献
197.
Isolation and Characterization of a Novel As(V)-Reducing Bacterium: Implications for Arsenic Mobilization and the Genus Desulfitobacterium 下载免费PDF全文
Allison Niggemyer Stefan Spring Erko Stackebrandt R. Frank Rosenzweig 《Applied microbiology》2001,67(12):5568-5580
Dissimilatory arsenate-reducing bacteria have been implicated in the mobilization of arsenic from arsenic-enriched sediments. An As(V)-reducing bacterium, designated strain GBFH, was isolated from arsenic-contaminated sediments of Lake Coeur d'Alene, Idaho. Strain GBFH couples the oxidation of formate to the reduction of As(V) when formate is supplied as the sole carbon source and electron donor. Additionally, strain GBFH is capable of reducing As(V), Fe(III), Se(VI), Mn(IV) and a variety of oxidized sulfur species. 16S ribosomal DNA sequence comparisons reveal that strain GBFH is closely related to Desulfitobacterium hafniense DCB-2T and Desulfitobacterium frappieri PCP-1T. Comparative physiology demonstrates that D. hafniense and D. frappieri, known for reductively dechlorinating chlorophenols, are also capable of toxic metal or metalloid respiration. DNA-DNA hybridization and comparative physiological studies suggest that D. hafniense, D. frappieri, and strain GBFH should be united into one species. The isolation of an Fe(III)- and As(V)-reducing bacterium from Lake Coeur d'Alene suggests a mechanism for arsenic mobilization in these contaminated sediments while the discovery of metal or metalloid respiration in the genus Desulfitobacterium has implications for environments cocontaminated with arsenious and chlorophenolic compounds. 相似文献
198.
199.
I. Bruce Rosenzweig Donald A. Wiebe Jacquelyn A. Hank John J. Albers Janet L. Adolphson Ernest Borden Earl S. Shrago Paul M. Sondel 《Biotherapy》1990,2(3):193-198
Six patients with confirmed malignant disease received four consecutive weekly cycles of human recombinant interleukin-2 (IL-2) 4 days/week, continuous iv. infusion, 3 × 106 U/m2/day. Plasma cholesterol decreased a mean of 7% within 24 hours after IL-2 infusion and decreased by 33% within 4 days. Plasma cholesterol was significantly lower than baseline concentration by day 21 (–21%), and day 25 (–41%) was significantly lower than day 21. Decreased plasma cholesterol was the result of decreased HDL and LDL cholesterol concentrations. Plasma triglyceride demonstrated a mean increase of 46% after 4 days of therapy and remained greater than baseline concentrations at all time points analyzed. Apolipoprotein AI and AII decreased concomitantly with HDL-cholesterol concentrations, whereas apolipoprotein B after an initial mean decrease of 17% during the first cycle was not significantly different from baseline during the fourth cycle. Apolipoprotein E and Lp(a) were not significantly affected by IL-2 treatment. Plasma C-reactive protein (CRP) increased by 79% within 24 hours of therapy, increased by 254% on day 4, then decreased to baseline concentrations by day 21 after 3 days off of IL-2. Day 25 CRP was elevated compared to both baseline and day 21 concentrations. IL-2 induced plasma lipoprotein changes may be due in part to the induction of interferon gamma. 相似文献
200.
R. Frank Rosenzweig Julian Adams 《BioEssays : news and reviews in molecular, cellular and developmental biology》1994,16(10):715-717
Recent work by Magnuson, Solomon and Grossman(1) adds to a growing body of evidence indicating that microorganisms possess sophisticated signaling systems that enable them to sense and respond to environmental challenges. Typically, this response results in morphological, physiological and even genetic differentiation, paralleling that observed among higher organisms. These signaling systems may be interpreted as adaptations that maximize the reproductive potential of a population. 相似文献