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991.
Zhou B Arnett DR Yu X Brewster A Sowd GA Xie CL Vila S Gai D Fanning E Chen XS 《The Journal of biological chemistry》2012,287(32):26854-26866
DNA polymerase α-primase (Pol-prim) plays an essential role in eukaryotic DNA replication, initiating synthesis of the leading strand and of each Okazaki fragment on the lagging strand. Pol-prim is composed of a primase heterodimer that synthesizes an RNA primer, a DNA polymerase subunit that extends the primer, and a regulatory B-subunit (p68) without apparent enzymatic activity. Pol-prim is thought to interact with eukaryotic replicative helicases, forming a dynamic multiprotein assembly that displays primosome activity. At least three subunits of Pol-prim interact physically with the hexameric replicative helicase SV40 large T antigen, constituting a simple primosome that is active in vitro. However, structural understanding of these interactions and their role in viral chromatin replication in vivo remains incomplete. Here, we report the detailed large T antigen-p68 interface, as revealed in a co-crystal structure and validated by site-directed mutagenesis, and we demonstrate its functional importance in activating the SV40 primosome in cell-free reactions with purified Pol-prim, as well as in monkey cells in vivo. 相似文献
992.
The number of proteasomal substrates that are degraded without prior ubiquitylation continues to grow. However, it remains poorly understood how the proteasome recognizes substrates lacking a ubiquitin (Ub) signal. Here we demonstrated that the Ub-independent degradation of Rpn4 requires the 19S regulatory particle (RP). The Ub-independent degron of Rpn4 was mapped to an N-terminal region including the first 80 residues. Inspection of its amino acid sequence revealed that the Ub-independent degron of Rpn4 consists of an intrinsically disordered domain followed by a folded segment. Using a photo-crosslinking-label transfer method, we captured three 19S RP subunits (Rpt1, Rpn2 and Rpn5) that bind the Ub-independent degron of Rpn4. This is the first time that specific 19S RP subunits have been identified interacting with a Ub-independent degron. This study provides insight into the mechanism by which Ub-independent substrates are recruited to the 26S proteasome. 相似文献
993.
C Xie Xc ZS Zhou X Xae Xee N Li Xe Y Bian X YJ Wang Xb Xc Xefa LJ Wang Xb Xed Xaf BL Li Xe Xff Xf BL Song Xbb Xfdd Xeae 《Journal of lipid research》2012,53(10):2092-2101
The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo. 相似文献
994.
Shankar SP Wilson MS DiVietro JA Mentink-Kane MM Xie Z Wynn TA Druey KM 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(12):6347-6356
The regulators of G protein signaling (RGS) protein superfamily negatively controls G protein-coupled receptor signal transduction pathways. RGS16 is enriched in activated/effector T lymphocytes. In this paper, we show that RGS16 constrains pulmonary inflammation by regulating chemokine-induced T cell trafficking in response to challenge with Schistosoma mansoni. Naive Rgs16(-/-) mice were "primed" for inflammation by accumulation of CCR10(+) T cells in the lung. Upon pathogen exposure, these mice developed more robust granulomatous lung fibrosis than wild-type counterparts. Distinct Th2 or putative Th17 subsets expressing CCR4 or CCR10 accumulated more rapidly in Rgs16(-/-) lungs following challenge and produced proinflammatory cytokines IL-13 and IL-17B. CCR4(+)Rgs16(-/-) Th2 cells migrated excessively to CCL17 and localized aberrantly in challenged lungs. T lymphocytes were partially excluded from lung granulomas in Rgs16(-/-) mice, instead forming peribronchial/perivascular aggregates. Thus, RGS16-mediated confinement of T cells to Schistosome granulomas mitigates widespread cytokine-mediated pulmonary inflammation. 相似文献
995.
S Su JD Chen HT Qi WJ Zhu JX Xie Z Huang LK Tan WB Qi GH Zhang 《Journal of virology》2012,86(17):9533
We report here the complete genomic sequence of a novel avian-like H3N2 swine influenza virus containing an H5N1 highly pathogenic avian influenza virus segment that was obtained from swine in southern China. Phylogenetic analysis indicated that this virus might originate from domestic aquatic birds. The sequence information provided herein suggests that continuing study is required to determine if this virus can be established in the swine population and pose potential threats to public health. 相似文献
996.
997.
998.
We evaluated the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to chronic obstructive pulmonary
disease (COPD) in smokers. A meta-analysis of the published case–control studies was performed. Published literature was retrieved
from PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI), with last update in February, 2011. Data were extracted
and a fixed- or random-effects model was used to calculate pooled odds ratios with 95% confidence intervals depending on statistical
heterogeneity. Fourteen eligible studies, comprising 1,665 COPD cases and 1,614 controls, were included in the meta-analysis.
The combined analyses showed that there was a significant difference in GSTM1 genotype distribution between COPD cases and
controls among Caucasians, but not among Asians. The combined GSTM1/GSTT1 null genotype conferred a 1.36-fold greater risk
for COPD in Asian smokers. The GSTT1 null genotype alone was not associated with enhanced risk for COPD. The GSTM1 null genotype
is significantly associated with an increasing susceptibility to COPD in Caucasian smokers, but not in Asian smokers. The
GSTM1/GSTT1 null genotype is a significant risk factor for developing COPD in Asian smokers. The GSTT1 null genotype, however,
was not associated with COPD. 相似文献
999.
Wang Y Ou YL Liu YQ Xie Q Liu QF Wu Q Fan TQ Yan LL Wang JY 《Biological trace element research》2012,145(2):127-135
In order to explore the associations between trace elements in dietary intake and the other three biological media (blood,
urine, or feces) and inter-element interactions among the latter, we simultaneously collected 72-h diet duplicates, whole
blood, and 72-h urine and feces from 120 free-living healthy males in China. Correlations among the toxic (cadmium [Cd], lead
[Pb]), and nutritionally essential (zinc [Zn], copper [Cu], iron [Fe], manganese [Mn], selenium [Se], iodine [I]) elements
were evaluated using Spearman rank correlation analysis based on analytical data determined by inductively coupled plasma-mass
spectrometry. Dietary Cd intakes were highly correlated with the fecal Cd and blood Cd levels. Inverse correlations were found
for Fe–Cd and Fe–Pb in both diet versus blood and diet versus feces. Cd–Zn and Cd–Se were significantly directly correlated
in the urine and feces. Cd–Se and Pb–Se were negatively correlated in blood. In addition, there existed an extremely significant
association between urinary Se and urinary I. Moreover, the other two highly direct correlations were found for Se–Fe and
for I–Fe in urine. Improved knowledge regarding their mutual associations is considered to be of fundamental importance to
understand more the complex interrelationships in trace element metabolism. 相似文献
1000.
Bing Li Yi Xie Zhe Cheng Jie Cheng Rengping Hu Suxin Gui Xuezi Sang Qingqing Sun Xiaoyang Zhao Lei Sheng Weide Shen Fashui Hong 《Biological trace element research》2012,150(1-3):221-228
Bombyx mori nucleopolyhedrovirus (BmNPV) causes infection in the silkworm that is often lethal. The infection is hard to prevent, partly because of the nature of the virus particles and partly because of the different strains of B. mori. Titanium dioxide nanoparticles (TiO2 NPs) have been demonstrated to have antimicrobial properties. The present study investigated whether TiO2 NPs added to an artificial diet can increase the resistance of B. mori larvae to BmNPV and examined the molecular mechanism behind any resistance shown. The results indicated that ingested TiO2 NPs decreased reactive oxygen species and NO accumulation in B. mori larvae under BmNPV infection, which in turn led to a decrease in their growth inhibition and mortality. In addition, the TiO2 NPs significantly promoted the expression of resistance-related genes, including those encoding superoxide dismutase, catalase, glutathione peroxidase, acetylcholine esterase, carboxylesterase, heat shock protein 21, glutathione S transferase o1, P53, and transferring and of genes encoding cytochrome p302 and nitric oxide synthase. These findings are a useful addition to the understanding of the mechanism of BmNPV resistance of B. mori larvae in response to TiO2 NPs addition. Such information also provides a theoretical basis for the use of TiO2 NPs in sericulture. 相似文献