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BackgroundDietary vitamin D3 (D3) restriction reduces paw grip endurance and motor performance in G93A mice, and increases inflammation and apoptosis in the quadríceps of females. ALS, a neuromuscular disease, causes progressive degeneration of motor neurons in the brain and spinal cord.ObjectiveWe analyzed the spinal cords of G93A mice following dietary D3 restriction at 2.5% the adequate intake (AI) for oxidative damage (4-HNE, 3-NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF-α, IL-6, IL-10), apoptosis (bax/bcl-2 ratio, cleaved/pro-caspase 3 ratio), neurotrophic factor (GDNF) and neuron count (ChAT, SMI-36/SMI-32 ratio).MethodsBeginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI;1 IU D3/g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D3/g feed; 10 M, 9 F) D3. At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P ≤ 0.10, since this was a pilot study.ResultsDEF mice had 16% higher 4-HNE (P = 0.056), 12% higher GPx1 (P = 0.057) and 23% higher Bax/Bcl2 ratio (P = 0.076) vs. AI. DEF females had 29% higher GPx1 (P = 0.001) and 22% higher IL-6 (P = 0.077) vs. AI females. DEF males had 23% higher 4-HNE (P = 0.066) and 18% lower SOD2 (P = 0.034) vs. AI males. DEF males had 27% lower SOD2 (P = 0.004), 17% lower GPx1 (P = 0.070), 29% lower IL-6 (P = 0.023) and 22% lower ChAT (P = 0.082) vs. DEF females.ConclusionD3 deficiency exacerbates disease pathophysiology in the spinal cord of G93A mice, the exact mechanisms are sex-specific. This is in accord with our previous results in the quadriceps, as well as functional and disease outcomes. 相似文献
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The highly orchestrated progression of the cell cycle depends on the degradation of many regulatory proteins at different cell cycle stages. One of the key cell cycle ubiquitin ligases is the Skp1-cullin-F-box (SCF) complex. Acting in concert with the substrate-binding F-box protein Grr1, SCFGrr1 promotes the degradation of cell cycle regulators as well as various metabolic enzymes. Using a yeast two-hybrid assay with a Grr1 derivative as the bait, we identified She3, which is an adaptor protein in the asymmetric mRNA transport system, as a novel Grr1 substrate. We generated stabilized She3 mutants, which no longer bound to Grr1, and found that the degradation of She3 is not required for regulating asymmetric mRNA transport. However, She3 stabilization leads to slower growth compared to wild-type cells in a co-culture assay, demonstrating that the degradation of She3 by Grr1 is required for optimal cell growth. 相似文献
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The growth on pseudouridine of two pyrimidine auxotrophs of Escherichia coli (Bu(-) and W63-86) was markedly enhanced when glycerol replaced glucose as a carbon source or when adenosine 3':5'-cyclic monophosphoric acid was added to medium containing glucose. These results indicated that an enzyme catalyzing a reaction in the pathway of pseudouridine conversion to uracil was sensitive to catabolite repression. The following pathway is proposed for pseudouridine utilization: [Formula: see text] [Formula: see text] Pseudouridylate synthetase was sensitive to catabolite repression in strains Bu(-) and W63-86. In contrast, strains B5RU and W5RU, mutants of Bu(-) and W63-86 which were selected for their ability to grow rapidly on pseudouridine in the presence of glucose, had high levels of pseudouridylate synthetase in the presence of glucose. In the case of B5RU but not W5RU, synthetase activity was greater in cells grown on glycerol or on glucose plus adenosine 3':5-cyclic monophosphoric acid than on glucose. 相似文献
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Aqueous pores in lipid bilayers and red cell membranes 总被引:1,自引:0,他引:1
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F J Stevens F A Westholm N Panagiotopoulos M Schiffer R A Popp A Solomon 《Journal of molecular biology》1981,147(1):185-193
A “naturally occurring” human κI VL dimer, designated Wat, has been isolated and crystallized. Protein Wat consists of two non-covalently bound monomers, each having a molecular weight of ~ 11,500. The monomer subunit is composed of an entire variable region light chain (VL) domain closely homologous to that of the κI Bence Jones protein Roy (Hilschmann &; Craig, 1965) as evidenced from amino acid composition, tryptic peptide map, and sequence analysis. Immunochemical studies substantiated that protein Wat is of the κ chain subgroup κI and lacks the isotypic and allotypic antigenic determinants associated with the κ constant region light chain domain. Two types of crystals of VL dimer Wat were obtained from ammonium sulfate or polyethylene glycol solutions. The type I crystals have unit cell dimensions of , and the space group is hexagonal P62 or P64. The asymmetric unit consists of one VL dimer; the fractional volume of unit cell occupied by solvent is 0.51. The unit cell dimensions of the type II crystals are ; the space group is hexagonal P6122 or P6522. Three variable domains constitute the asymmetric unit of the type II crystals; the fractional value of the solvent (0.52) is compatible with the value obtained for the type I crystals. 相似文献
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Assessing changes over time in healthcare provider performance: Addressing regression to the mean over multiple time points 下载免费PDF全文
Jessica Kasza John L. Moran Patricia J. Solomon 《Biometrical journal. Biometrische Zeitschrift》2015,57(2):271-285
In recent years, the evaluation of healthcare provider performance has become standard for governments, insurance companies, and other stakeholders. Often, performance is compared across providers using indicators in one time period, for example a year. However it is often important to assess changes in the performance of individual providers over time. Such analyses can be used to determine if any providers have significant improvements, deteriorations, unusual patterns or systematic changes in performance. Studies which monitor healthcare provider performance in this way have to date typically been limited to comparing performance in the most recent period with performance in a previous period. It is also important to consider a longer‐term view of performance and assess changes over more than two periods. In this paper, we develop test statistics that account for variable numbers of prior performance indicators, and show that these are particularly useful for assessing consecutive improvements or deteriorations in performance. We apply the tests to coronary artery bypass graft mortality rates in New York State hospitals, and mortality data from Australian and New Zealand intensive care units. Although our applications are to medical data, the new tests have broad application in other areas. 相似文献