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21.
Pasiakos SM Karl JP Lutz LJ Murphy NE Margolis LM Rood JC Cable SJ Williams KW Young AJ McClung JP 《PloS one》2012,7(2):e31222
Background
Cardiometabolic disease risk in US military recruits and the effects of military training have not been determined. This study examined lifestyle factors and biomarkers associated with cardiometabolic risk in US Army recruits (209; 118 male, 91 female, 23±5 yr) before, during, and after basic combat training (BCT).Methodology/Principal Findings
Anthropometrics; fasting total (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; triglycerides (TG); glucose; and insulin were measured at baseline and every 3 wks during the 10 wk BCT course. At baseline, 14% of recruits were obese (BMI>30 kg/m2), 27% were cigarette smokers, 37% were sedentary, and 34% reported a family history of cardiometabolic disease. TC was above recommended levels in 8%, LDL in 39%, TG in 5%, and glucose in 8% of recruits, and HDL was below recommended levels in 33% of recruits at baseline. By week 9, TC decreased 8%, LDL 10%, TG 13%, glucose 6% and homeostasis model assessment of insulin resistance (HOMA-IR) 40% in men (P<0.05). In women, TC, LDL, glucose and HOMA-IR were decreased from baseline at weeks 3 and 6 (P<0.05), but were not different from baseline levels at week 9. During BCT, body weight declined in men but not women, while body fat percentage declined in both men and women (P<0.05).Conclusions/Significance
At the start of military service, the prevalence of cardiometabolic risk in US military recruits is comparable to that reported in similar, college-aged populations. Military training appears to be an effective strategy that may mitigate risk in young people through improvements in lipid profiles and glycemic control. 相似文献22.
Krishna Jafa Peter McElroy Lisa Fitzpatrick Craig B. Borkowf Robin MacGowan Andrew Margolis Ken Robbins Ae Saekhou Youngpairoj Dale Stratford Alan Greenberg Jennifer Taussig R. Luke Shouse Madeleine LaMarre Eleanor McLellan-Lemal Walid Heneine Patrick S. Sullivan 《PloS one》2009,4(5)
Introduction
HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988–2005 among male Georgia prison inmates.Methods
We analyzed medical and administrative data to describe seroconverters'' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters'' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks.Results
Forty-one (47%) seroconverters were diagnosed with HIV from July 2003–June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0–0.10) and tattooing (OR = 0.03, 95% CI: <0.01–0.20) in prison after their HIV diagnosis than before. Of 67 seroconverters'' specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant.Discussion
Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates. 相似文献23.
Margolis RL 《Developmental cell》2004,7(5):634-635
The mitotic spindle assembly checkpoint arrests cells at metaphase by suppressing Cdc20, a protein required to trigger ubiquitination and consequent degradation of cyclin B. New evidence from Tang et al. appearing in the November 5th issue of Molecular Cell finds that one of the checkpoint proteins, Bub1, specifically phosphorylates Cdc20 to suppress APC/C activation. 相似文献
24.
Michael McGregor Nirmala Hariharan Anya Joyo Robert L Margolis 《Cell cycle (Georgetown, Tex.)》2014,13(5):739-748
Centromere protein A (CENP-A) is a homolog of histone H3 that epigenetically marks the heterochromatin of chromosomes. CENP-A is a critical component of the cell cycle machinery that is necessary for proper assembly of the mitotic spindle. However, the role of CENP-A in the heart and cardiac progenitor cells (CPCs) has not been previously studied. This study shows that CENP-A is expressed in CPCs and declines with age. Silencing CENP-A results in a decreased CPC growth rate, reduced cell number in phase G2/M of the cell cycle, and increased senescence associated β-galactosidase activity. Lineage commitment is not affected by CENP-A silencing, suggesting that cell cycle arrest induced by loss of CENP-A is a consequence of senescence and not differentiation. CENP-A knockdown does not exacerbate cell death in undifferentiated CPCs, but increases apoptosis upon lineage commitment. Taken together, these results indicate that CPCs maintain relatively high levels of CENP-A early in life, which is necessary for sustaining proliferation, inhibiting senescence, and promoting survival following differentiation of CPCs. 相似文献
25.
A current focus of research in neurobiology is to define themechanisms by
which neurons reach their final destination andacquire their differentiated
phenotype. An ideal model for thesestudies is the olfactory system, where
nasal placodally derivedgonadotropin-releasing hormone (GnRH) neurons,
olfactory receptorneurons and interneurons 相似文献
26.
Howes KA Pennesi ME Sokal I Church-Kopish J Schmidt B Margolis D Frederick JM Rieke F Palczewski K Wu SM Detwiler PB Baehr W 《The EMBO journal》2002,21(7):1545-1554
Visual transduction in retinal photoreceptors operates through a dynamic interplay of two second messengers, Ca(2+) and cGMP. Ca(2+) regulates the activity of guanylate cyclase (GC) and the synthesis of cGMP by acting on a GC-activating protein (GCAP). While this action is critical for rapid termination of the light response, the GCAP responsible has not been identified. To test if GCAP1, one of two GCAPs present in mouse rods, supports the generation of normal flash responses, transgenic mice were generated that express only GCAP1 under the control of the endogenous promoter. Paired flash responses revealed a correlation between the degree of recovery of the rod a-wave and expression levels of GCAP1. In single cell recordings, the majority of the rods generated flash responses that were indistinguishable from wild type. These results demonstrate that GCAP1 at near normal levels supports the generation of wild-type flash responses in the absence of GCAP2. 相似文献
27.
PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone 总被引:23,自引:0,他引:23
Mollinari C Kleman JP Jiang W Schoehn G Hunter T Margolis RL 《The Journal of cell biology》2002,157(7):1175-1186
Midzone microtubules of mammalian cells play an essential role in the induction of cell cleavage, serving as a platform for a number of proteins that play a part in cytokinesis. We demonstrate that PRC1, a mitotic spindle-associated Cdk substrate that is essential to cell cleavage, is a microtubule binding and bundling protein both in vivo and in vitro. Overexpression of PRC1 extensively bundles interphase microtubules, but does not affect early mitotic spindle organization. PRC1 contains two Cdk phosphorylation motifs, and phosphorylation is possibly important to mitotic suppression of bundling, as a Cdk phosphorylation-null mutant causes extensive bundling of the prometaphase spindle. Complete suppression of PRC1 by siRNA causes failure of microtubule interdigitation between half spindles and the absence of a spindle midzone. Truncation mutants demonstrate that the NH2-terminal region of PRC1, rich in alpha-helical sequence, is important for localization to the cleavage furrow and to the center of the midbody, whereas the central region, with the highest sequence homology between species, is required for microtubule binding and bundling activity. We conclude that PRC1 is a microtubule-associated protein required to maintain the spindle midzone, and that distinct functions are associated with modular elements of the primary sequence. 相似文献
28.
Heilmann S Hummel T Margolis FL Kasper M Witt M 《Histochemistry and cell biology》2000,113(3):241-245
The expression pattern of galectin-1 and galectin-3 in the human olfactory epithelium was investigated in relation to olfactory
marker protein (OMP) using confocal laser immunofluorescence in human specimens and postmortem biopsies. OMP expression was
found in olfactory receptor neurons (ORNs) in the olfactory mucosa and in fibers of the olfactory nerve crossing the submucous
connective tissue. Galectin-1 was expressed in both the connective tissue of the nasal cavity and in the basal layer of the
olfactory epithelium. In contrast, galectin-3 expression was limited to cells of the upper one-third of the olfactory epithelium.
Expression of galectin-3 occurred in a subset of OMP-positive cells. However, between areas of galectin-1 and galectin-3 expression
in the lower and upper portion of the epithelium, OMP-positive ORNs did not stain for both galectins. Considering the potential
role of galectin-1 and galectin-3 in cell differentiation and maturation, the differential localization of galectins in the
olfactory epithelium appears to be consistent with a significant role of these molecules in the physiological turnover of
ORNs.
Accepted: 20 December 1999 相似文献
29.
Mueller HT Borg JP Margolis B Turner RS 《The Journal of biological chemistry》2000,275(50):39302-39306
Modulation of amyloid precursor protein (APP) metabolism plays a pivotal role in the pathogenesis of Alzheimer's disease. The phosphotyrosine-binding/protein interaction (PTB/PI) domain of X11alpha, a neuronal cytosolic adaptor protein, binds to the YENPTY sequence in the cytoplasmic carboxyl terminus of APP. This interaction prolongs the half-life of APP and inhibits Abeta40 and Abeta42 secretion. X11alpha/Mint-1 has multiple protein-protein interaction domains, a Munc-18 interaction domain (MID), a Cask/Lin-2 interaction domain (CID), a PTB/PI domain, and two PDZ domains. These X11alpha protein interaction domains may modulate its effect on APP processing. To test this hypothesis, we performed a deletion analysis of X11alpha effects on metabolism of APP(695) Swedish (K595N/M596L) (APP(sw)) by transient cotransfection of HEK 293 cells with: 1) X11alpha (X11alpha-wt, N-MID-CID-PTB-PDZ-PDZ-C), 2) amino-terminal deletion (X11alpha-DeltaN, PTB-PDZ-PDZ), 3) carboxyl-terminal deletion (X11alpha-DeltaPDZ, MID-CID-PTB), or 4) deletion of both termini (PTB domain only, PTB). The carboxyl terminus of X11alpha was required for stabilization of APP(sw) in cells. In contrast, the amino terminus of X11alpha was required to stimulate APPs secretion. X11alpha, X11alpha-DeltaN, and X11alpha-PTB, but not X11alpha-DeltaPDZ, were effective inhibitors of Abeta40 and Abeta42 secretion. These results suggest that additional protein interaction domains of X11alpha modulate various aspects of APP metabolism. 相似文献
30.
Kamberov E Makarova O Roh M Liu A Karnak D Straight S Margolis B 《The Journal of biological chemistry》2000,275(15):11425-11431
In Caenorhabditis elegans, three PDZ domain proteins, Lin-2, Lin-7, and Lin-10, are necessary for the proper targeting of the Let-23 growth factor receptor to the basolateral surface of epithelial cells. It has been demonstrated that homologues of Lin-2, Lin-7, and Lin-10 form a heterotrimeric complex in mammalian brain. Using Far Western overlay assay, we have identified additional proteins that can bind to the amino terminus of mLin-7 and cloned the genes encoding these proteins using bacterial expression cloning. We call these proteins Pals, for proteins associated with Lin-7. These proteins, which include mammalian Lin-2, contain a conserved mLin-7 binding domain in addition to guanylate kinase, PDZ (postsynaptic density 95/discs large/zona occludens-1), and Src homology 3 domains. Using site-directed mutagenesis, we have identified the conserved residues among these proteins crucial for mLin-7 binding. Two of these proteins, Pals1 and Pals2, are newly described. Pals1 consists of 675 amino acids and maps to mouse chromosome 12. Pals2 was found to exist in two splice forms of 539 and 553 amino acids and maps to mouse chromosome 6. Like mLin-2, Pals1 and Pals2 localize to the lateral membrane in Madin-Darby canine kidney cells. Pals proteins represent a new subfamily of membrane-associated guanylate kinases that allow for multiple targeting complexes containing mLin-7. 相似文献