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11.
The mouse hnRNP A2/B1/B0 gene has been cloned using a PCR-based strategy and sequenced. Analysis of this sequence showed that the gene organization closely follows that of the human orthologue with 12 exons and 11 introns. The hnRNP A2/B1/B0 gene gives rise to four splice variants through alternative splicing of exons 2 and 9. RT-PCR assays indicated that all splice variants were expressed in mouse brain, skin, and stomach tissues of varying ages, although their ratios to one another varied with age and tissue type. We also identified a small subset of all polyadenylated splice variants that included intron 11, which shows 94% sequence identity between human and mouse. Several processed pseudogenes were identified in the mouse genome. A search of the mouse genome databases located five pseudogenes, four of which are presumed to be non-functional because of the presence of premature stop codons, large deletions or rearrangements within the coding region. The fifth, which possesses putative promoter elements and has a coding sequence identical to that of the hnRNP A2 mRNA variant, may be functional. 相似文献
12.
CD4 T-cell-mediated demyelination is increased in the absence of gamma interferon in mice infected with mouse hepatitis virus
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Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. Adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected mice deficient in recombination activation gene 1 resulted in demyelination. We showed previously that the process of CD8 T-cell-mediated demyelination was strongly dependent on the expression of gamma interferon (IFN-gamma) by donor cells. In this report, we show, in contrast, that demyelination and lymphocyte infiltration were increased in recipients of IFN-gamma(-/-) CD4 T cells when compared to levels in mice receiving C57BL/6 CD4 T cells. 相似文献
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14.
Objectives
We aimed to describe and compare the prevalence of vitamin D deficiency between HIV-negative and HIV-infected veterans in the southern United States, and to determine risk factors for vitamin D deficiency for HIV infected patients.Methods
Cross-sectional, retrospective study including all patients followed at the Atlanta VA Medical Center with the first 25-hydroxyvitamin D [25(OH)D] level determined between January 2007 and August 2010. Multivariate logistic regression analysis was used to determine risk factors associated with vitamin D deficiency (< 20 ng/ml).Results
There was higher prevalence of 25(OH)D deficiency among HIV-positive compared to HIV-negative patients (53.2 vs. 38.5%, p <0.001). Independent risk factors for vitamin D deficiency in HIV + patients included black race (OR 3.24, 95% CI 2.28–4.60), winter season (OR 1.39, 95% CI 1.05–1.84) and higher GFR (OR 1.01, CI 1.00–1.01); increasing age (OR 0.98, 95% CI 0.95–0.98), and tenofovir use (OR 0.72, 95% CI 0.54–0.96) were associated with less vitamin D deficiency.Conclusions
Vitamin D deficiency is a prevalent problem that varies inversely with age and affects HIV-infected patients more than other veterans in care. In addition to age, tenofovir and kidney disease seem to confer a protective effect from vitamin D deficiency in HIV-positive patients. 相似文献15.
16.
Steven T. Staben Timothy P. Heffron Daniel P. Sutherlin Seema R. Bhat Georgette M. Castanedo Irina S. Chuckowree Jenna Dotson Adrian J. Folkes Lori S. Friedman Leslie Lee John Lesnick Cristina Lewis Jeremy M. Murray Jim Nonomiya Alan G. Olivero Emile Plise Jodie Pang Wei Wei Prior Laurent Salphati Lionel Rouge Bing-Yan Zhu 《Bioorganic & medicinal chemistry letters》2010,20(20):6048-6051
Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model. 相似文献
17.
In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept - best left
to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world,
practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural
measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as
43%) - clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that
do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation
of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome). Based on the evidence
to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation
of residual function, formation of differential diagnoses, and estimation of prognosis. 相似文献
18.
High cytosolic concentrations of Na+ inhibit plant growth and development. To maintain low cytosolic concentrations of Na+ , higher plants use membrane-bound transporters that drive the efflux of Na+ or partition Na+ ions from the cytosol, either to the extracellular compartment or into the vacuole. Bryophytes also use an energy-dependent Na+ pumping ATPase, not found in higher plants, to efflux Na+ . To investigate whether this transporter can increase the salt tolerance of crop plants, Oryza sativa has been transformed with the Physcomitrella patens Na+ pumping ATPase (PpENA1). When grown in solutions containing 50 mm NaCl, plants constitutively expressing the PpENA1 gene are more salt tolerant and produce greater biomass than controls. Transgenics and controls accumulate similar amounts of Na+ in leaf and root tissues under stress, which indicates that the observed tolerance is not because of Na+ exclusion. Moreover, inductively coupled plasma analysis reveals that the concentration of other ions in the transformants and the controls is similar. The transgenic lines are developmentally normal and fertile, and the transgene expression levels remain stable in subsequent generations. GFP reporter fusions, which do not alter the ability of PpENA1 to complement a salt-sensitive yeast mutant, indicate that when it is expressed in plant tissues, the PpENA1 protein is located in the plasma membrane. PpENA1 peptides are found in plasma membrane fractions supporting the plasma membrane targeting. The results of this study demonstrate the utility of PpENA1 as a potential tool for engineering salinity tolerance in important crop species. 相似文献
19.
Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1−/− C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1−/− mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1−/− mammary glands. Additionally, pseudopregnant Akt1−/− females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function. 相似文献
20.
Carland M Tan KJ White JM Stephenson J Murray V Denny WA McFadyen WD 《Journal of inorganic biochemistry》2005,99(8):1738-1743
The cationic complexes (1,2-diaminoethane)(maltolato)platinum(II) ([Pt(en)(ma)]+) and (1R,2R-1,2-diaminocyclohexane)(maltolato)platinum(II) ([Pt(R,R-DACH)(ma)]+) have been prepared and the structure of [Pt(R,R-DACH)(ma)]NO3 has been determined by single crystal X-ray diffraction. The geometry of the metal in [Pt(R,R-DACH)(ma)]NO3 is essentially square planar and the maltolate ligand has a geometry similar to other chelate complexes involving this ligand. The cytotoxicities of the compounds have been assessed in the human cell lines HeLa and K562 and the IC50 values are approximately 32 microM in HeLa cells and 26 microM in K562 cells. In these cell lines the cytotoxicity of cisplatin is higher than the maltolate complexes by a factor of 2 to 3 whereas the cytotoxicity of carboplatin is lower than the maltolate complexes. 相似文献