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91.
Vascular endothelium in atherosclerosis 总被引:1,自引:0,他引:1
Their strategic location between blood and tissue and their constitutive properties allow endothelial cells (EC) to monitor
the transport of plasma molecules, by employing bidirectional receptor-mediated and receptor-independent transcytosis and
endocytosis, and to regulate vascular tone, cellular cholesterol and lipid homeostasis. These cells are also involved in signal
transduction, immunity, inflammation and haemostasis. Cardiovascular risk factors, such as hyperlipaemia/dyslipidaemia trigger
the molecular machinery of EC to respond to insults by modulation of their constitutive functions followed by dysfunction
and ultimately by injury and apoptosis. The gradual activation of EC consists initially in the modulation of two constitutive
functions: (1) permeability, i.e. increased transcytosis of lipoproteins, and (2) biosynthetic activity, i.e. enhanced synthesis
of the basement membrane and extracellular matrix. The increased transcytosis and the reduced efflux of β-lipoproteins (βLp)
lead to their retention within the endothelial hyperplasic basal lamina as modified lipoproteins (MLp) and to their subsequent
alteration (oxidation, glycation, enzymatic modifications). MLp generate chemoattractant and inflammatory molecules, triggering
EC dysfunction (appearance of new adhesion molecules, secretion of chemokines, cytokines), characterised by monocyte recruitment,
adhesion, diapedesis and residence within the subendothelium. In time, EC in the athero-prone areas alter their net negative
surface charge, losing their non-thrombogenic ability, become loaded with lipid droplets and turn into foam cells. Prolonged
and/or repeated exposure to cardiovascular risk factors can ultimately exhaust the protective effect of the endogenous anti-inflammatory
system within EC. As a consequence, EC may progress to senescence, lose their integrity and detach into the circulation. 相似文献
92.
Seyyed Javad Sabounchei Hassan Nemattalab Sima Khani Harry Adams 《Inorganica chimica acta》2009,362(1):105-2492
The reactions of phosphorus ylide (p-tolyl)3PCHC(O)CH3 (Y1) with HgX2 (X = Cl and Br) and (p-tolyl)3PCHC(O)C6H4NO2 (Y2) with HgX2 (X = Cl, Br and I) in equimolar ratios using methanol as a solvent are reported. These reactions led to binuclear complexes. C-Coordination of ylides and trans-like structure of complexes [(Y1) · HgBr2]2 and [(Y2) · HgBr2]2 · 2DMSO are demonstrated by single crystal X-ray analyses. The IR, 1H, 13C and 31P NMR data for the other synthesized compounds are similar to the latter complexes, indicating similar structures. Elemental analyses indicate a 1:1 stoichiometry between the ylide and Hg(II) halide in all the products. The ab initio studies indicated that for all dimeric compounds, the observed trans-like structures are 7-10 kcal/mol more stable than the alternative possible cis-like isomers. Although the calculated bond lengths are slightly longer than the measured ones, the similarity of calculated and measured bond angles reflects the similar geometrical structures for these compounds in both the solid state and the gas phase. 相似文献
93.
Rubin DL Lewis SE Mungall CJ Misra S Westerfield M Ashburner M Sim I Chute CG Solbrig H Storey MA Smith B Day-Richter J Noy NF Musen MA 《Omics : a journal of integrative biology》2006,10(2):185-198
The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. 相似文献
94.
95.
The activity of S-adenosylmethionine decarboxylase (AdoMetDC) in Crithidia fasciculata was shown to be correlated to the growth of the parasite. An increase in activity was observed during exponential growth. Inhibition of protein synthesis induced an extremely rapid decay of AdoMetDC activity. The half-life of the enzyme was estimated to be about 3 min, which is the shortest half-life ever recorded for an eukaryotic AdoMetDC. The reduction in AdoMetDC activity was correlated with a decrease in AdoMetDC protein content, demonstrating a rapid turnover of the enzyme. No polyamine-mediated feedback regulation of AdoMetDC was observed in the parasite. 相似文献
96.
Dermaseptin S4 and its substituted derivative K(4)-S4 were investigated against various food-related pathogenic bacteria in culture media. K(4)-S4, but not the native peptide displayed significant growth inhibitory activity against all bacteria tested. Next, activity of K(4)-S4 against Escherichia coli O157:H7 was defined in terms of milieu dependencies. Salt-dependent kinetic studies in growth medium indicated that the peptide's antibacterial activity is maintained at fairly high (up to 600mM) NaCl concentrations but inhibited at higher concentrations. Similarly, antibacterial activity was reduced at high but not low pH conditions. Importantly, antibacterial activity was significantly maintained at temperatures lower than 37 degrees C and significantly enhanced at 42 degrees C. With respect to bactericidal kinetics, negative cultures were obtained in LB as well as in commercial apple juice, respectively, within 1 and 2h treatment, at twice the minimal inhibitory concentration (MIC) value. Overall, the data collected is indicative of a certain interest for dermaseptin derivatives as potential food preservatives. 相似文献
97.
Sadray S Rezaee S Rezakhah S 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,787(2):293-302
Generalized least squares regression with variance function estimation was used to derive the calibration function for measurement of methotrexate plasma concentration and its results were compared with weighted least squares regression by usual weight factors and also with that of ordinary least squares method. In the calibration curve range of 0.05 to 100 microM, both heteroscedasticity and non-linearity were present therefore ordinary least squares linear regression methods could result in large errors in the calculation of methotrexate concentration. Generalized least squares regression with variance function estimation worked better than both the weighted regression with the usual weight factors and ordinary least squares regression and gave better estimates for methotrexate concentration. 相似文献
98.
Annotation of the Drosophila melanogaster euchromatic genome: a systematic review 总被引:1,自引:0,他引:1
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Misra S Crosby MA Mungall CJ Matthews BB Campbell KS Hradecky P Huang Y Kaminker JS Millburn GH Prochnik SE Smith CD Tupy JL Whitfied EJ Bayraktaroglu L Berman BP Bettencourt BR Celniker SE de Grey AD Drysdale RA Harris NL Richter J Russo S Schroeder AJ Shu SQ Stapleton M Yamada C Ashburner M Gelbart WM Rubin GM Lewis SE 《Genome biology》2002,3(12):research0083.1-8322
99.
Dhaarmini Rajshankar Corneliu Sima Qin Wang Stephanie R. Goldberg Mwayi Kazembe Yongqiang Wang Michael Glogauer Gregory P. Downey Christopher A. McCulloch 《PloS one》2013,8(8)
IL-1β contributes to connective tissue destruction in part by up-regulating stromelysin-1 (MMP-3), which in fibroblasts is a focal adhesion-dependent process. Protein tyrosine phosphatase-α (PTPα) is enriched in and regulates the formation of focal adhesions, but the role of PTPα in connective tissue destruction is not defined. We first examined destruction of periodontal connective tissues in adult PTPα+/+ and PTPα−/− mice subjected to ligature-induced periodontitis, which increases the levels of multiple cytokines, including IL-1β. Three weeks after ligation, maxillae were processed for morphometry, micro-computed tomography and histomorphometry. Compared with unligated controls, there was ∼1.5–3 times greater bone loss as well as 3-fold reduction of the thickness of the gingival lamina propria and 20-fold reduction of the amount of collagen fibers in WT than PTPα−/− mice. Immunohistochemical staining of periodontal tissue showed elevated expression of MMP-3 at ligated sites. Second, to examine mechanisms by which PTPα may regulate matrix degradation, human MMP arrays were used to screen conditioned media from human gingival fibroblasts treated with vehicle, IL-1β or TNFα. Although MMP-3 was upregulated by both cytokines, only IL-1β stimulated ERK activation in human gingival fibroblasts plated on fibronectin. TIRF microscopy and immunoblotting analyses of cells depleted of PTPα activity with the use of various mutated constructs or with siRNA or PTPαKO and matched wild type fibroblasts were plated on fibronectin to enable focal adhesion formation and stimulated with IL-1β. These data showed that the catalytic and adaptor functions of PTPα were required for IL-1β-induced focal adhesion formation, ERK activation and MMP-3 release. We conclude that inflammation-induced connective tissue degradation involving fibroblasts requires functionally active PTPα and in part is mediated by IL-1β signaling through focal adhesions. 相似文献
100.
The effect of C-terminal fragment of JNK2 on the stability of p53 and cell proliferation 总被引:3,自引:0,他引:3
The basal activity of JNK is low in normal growing cells and inactivated JNK targets p53 for ubiquitination. To elucidate if the C-terminal part of JNK is responsible for its binding to p53, the low background tet-off inducible NIH3T3 cell line was selected by luciferase reporter gene and a double stable C-JNK Aa (203-424) cell line was established. After withdrawing tetracycline, the C-JNK fragment expression was induced and cell growth was dramatically inhibited 24 h later. However, the expresion of p53 was found to be increased after the induction of C-JNK fragment, evaluated by transfecting p21^waf-luciferase reporter genes. Our further studies showed that C-JNK fragment could form complex with p53 both in vivo and in vitro. Induction of C-JNK fragment in vivo can increase p53 stability by inhibiting p53 ubiquitination. 相似文献