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71.
Huang G Wang D Khan UI Zeb I Manson JE Miller V Hodis HN Budoff MJ Merriam GR Harman SM Brinton EA Cedars MI Lobo RA Naftolin F Santoro N Taylor HS Wildman RP Su Y 《Cardiovascular diabetology》2012,11(1):52
ABSTRACT: BACKGROUND: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard Western Blot analysis of RBP4 levels. METHODS: Full-length serum RBP4 levels were measured by Western Blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). RESULTS: The mean age of women was 52.9 (+/- 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) ug/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient= 0.10; P=0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients [less than or equal to]0.06, P>0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P=0.10). CONCLUSIONS: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. Trial Registration: ClinicalTrials.gov number NCT00154180. 相似文献
72.
73.
The G5 domain: a potential N-acetylglucosamine recognition domain involved in biofilm formation 总被引:1,自引:0,他引:1
SUMMARY: Biofilms are complex microbial communities found at surfaces that are often associated with extracellular polysaccharides. Biofilm formation is a complex process that is being understood at the molecular level only recently. We have identified a novel domain that we call the G5 domain (named after its conserved glycine residues), which is found in a variety of enzymes such as Streptococcal IgA peptidases and various glycosyl hydrolases in bacteria. The G5 domain is found in the Accumulation Associated Protein (AAP), which is an important component in biofilm formation in Staphylococcus aureus. A common feature of the proteins containing G5 domains is N-acetylglucosamine binding, and we attribute this function to the G5 domain. CONTACT: agb@sanger.ac.uk. 相似文献
74.
75.
Dynamics of T cells and TCR excision circles differ after treatment of acute and chronic HIV infection 总被引:5,自引:0,他引:5
Lewin SR Ribeiro RM Kaufmann GR Smith D Zaunders J Law M Solomon A Cameron PU Cooper D Perelson AS 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(8):4657-4666
We quantified T cell proliferation and thymic function in primary HIV infection (PHI; n = 19) and chronic HIV infection (CHI; n = 14) by measuring Ki67 staining and TCR excision circle (TREC) number. After antiretroviral therapy of PHI there is a profound decrease in the number and percentage of Ki67(+) T cells (<6% Ki67(+)) with no significant increase in TREC per million cells and a transient increase in TREC per milliliter. In contrast, after antiretroviral therapy of CHI there is a reduction in the percentage but little change in the total number of Ki67(+)CD4(+) T cells associated with increases in both TREC per million cells and TREC per milliliter. Using a mathematical model that accounts for proliferation, death, and redistribution of T cells, we find that redistribution is consistent with the TREC changes observed during treatment of PHI and that an increase in thymic output is needed to explain the increase in TREC during treatment of CHI. Consideration of TREC per milliliter shows that changes in proliferation alone cannot explain the changes in TREC. In addition, although increased proliferation of memory cells in HIV infection has been established, we find no difference in TREC per million CD45RA(-) "memory" T cells between healthy and infected individuals (p = 0.154 for CD4(+); p = 0.383 for CD8(+)). Finally, although the number of TREC per million cells is always much lower in memory T cells than in naive T cells, in the setting of HIV infection, given that memory cells make up a larger proportion of total T cells, we find that 50% of TREC per milliliter in CD4(+) T cells is harbored in the CD45RA(-) "memory" subset of our infected subjects. 相似文献
76.
Dhaval P. Bhatt C. Allie Mills Kristin A. Anderson Brbara J. Henriques Tnia G. Lucas Sara Francisco Juan Liu Olga R. Ilkayeva Alexander E. Adams Shreyas R. Kulkarni Donald S. Backos Michael B. Major Paul A. Grimsrud Cludio M. Gomes Matthew D. Hirschey 《The Journal of biological chemistry》2022,298(4)
A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity. 相似文献
77.
Fisher AC Kim W DeLisa MP 《Protein science : a publication of the Protein Society》2006,15(3):449-458
One of the most vexing problems facing structural genomics efforts and the biotechnology enterprise in general is the inability to efficiently produce functional proteins due to poor folding and insolubility. Additionally, protein misfolding and aggregation has been linked to a number of human diseases, such as Alzheimer's. Thus, a robust cellular assay that allows for direct monitoring, manipulation, and improvement of protein folding could have a profound impact. We report the development and characterization of a genetic selection for protein folding and solubility in living bacterial cells. The basis for this assay is the observation that protein transport through the bacterial twin-arginine translocation (Tat) pathway depends on correct folding of the protein prior to transport. In this system, a test protein is expressed as a tripartite fusion between an N-terminal Tat signal peptide and a C-terminal TEM1 beta-lactamase reporter protein. We demonstrate that survival of Escherichia coli cells on selective medium expressing a Tat-targeted test protein/beta-lactamase fusion correlates with the solubility of the test protein. Using this assay, we isolated solubility-enhanced variants of the Alzheimer's Abeta42 peptide from a large combinatorial library of Abeta42 sequences, thereby confirming that our assay is a highly effective selection tool for soluble proteins. By allowing the bacterial Tat pathway to exert folding quality control on expressed target protein sequences, we have generated a powerful tool for monitoring protein folding and solubility in living cells, for molecular engineering of solubility-enhanced proteins or for the isolation of factors and/or cellular conditions that stabilize aggregation-prone proteins. 相似文献
78.
Matthew A Schrager E Jeffrey Metter Eleanor Simonsick Alessandro Ble Stefania Bandinelli Fulvio Lauretani Luigi Ferrucci 《Journal of applied physiology》2007,102(3):919-925
The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as "sarcopenic obesity" (Roubenoff R. Ann NY Acad Sci 904: 553-557, 2000). Research suggests that inflammatory cytokines produced by adipose tissue, especially visceral fat, accelerate muscle catabolism and thus contribute to the vicious cycle that initiates and sustains sarcopenic obesity. We tested the hypothesis that obesity and poor muscle strength, hallmarks of sarcopenic obesity, are associated with high circulating levels of proinflammatory cytokines in a random sample of the residents of two municipalities in the Chianti geographic area (Tuscany, Italy). The study sample consisted of 378 men and 493 women 65 yr and older with complete data on anthropometrics, handgrip strength, and inflammatory markers. Participants were cross-classified according to sex-specific tertiles of waist circumference and grip strength and according to a cut point for obesity of body mass index > or =30 kg/m(2). After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated levels of IL-6, C-reactive protein, IL-1 receptor antagonist, and soluble IL-6 receptor (P < 0.05). Our findings suggest that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity. These results suggest that proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity. 相似文献
79.
80.
Leilani M. Lehmann Sean E. Walker† & Matthew H. Persons 《Ethology : formerly Zeitschrift fur Tierpsychologie》2004,110(4):323-339
The wolf spider, Pardosa milvina, reduces activity in the presence of chemical cues (silk and excreta) from a larger predatory wolf spider, Hogna helluo. Hogna is sexually dimorphic in body size and males and females differ in their propensity to attack prey. Consequently, each sex may present different levels of risk to Pardosa. We measured predation risk of Pardosa in the presence of male or female Hogna. We also assessed Pardosa antipredator responses and survival in the presence or absence of previously deposited chemical cues from male or female Hogna. In the absence of predator chemical cues, Pardosa survived significantly longer in the presence of male Hogna compared with female Hogna. We then assessed Pardosa survival in the presence of chemical cues from each Hogna sex by placing Pardosa in containers previously occupied by a female Hogna, a male Hogna, or no Hogna (control). We then introduced a female Hogna into each container and measured predation latency. Pardosa survived significantly longer in the presence of female and male cues compared with the control treatment. Median survival time of Pardosa was over four times longer on substrates with female Hogna cues compared with male cues, but this difference was not statistically significant. We tested Pardosa activity levels in the presence of chemical cues from male or female Hogna. Both Hogna sexes were maintained in separate containers after which we placed an adult female Pardosa in one of the containers or a blank control container. Pardosa significantly decreased activity in the presence of chemical cues from either sex relative to the control. Activity was lowest on substrates with female Hogna cues, but not significantly lower than on substrates with male Hogna cues. Results suggest that chemical information from male or female Hogna significantly reduces Pardosa activity which results in increased survival. 相似文献