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排序方式: 共有8593条查询结果,搜索用时 15 毫秒
931.
Objective
To investigate white matter volume abnormalities in patients with major depression and the effects of antidepressant treatment on white matter volume.Method
Magnetic resonance imaging (MRI) was performed on 32 treatment-naïve depressed patients, 17 recovered patients who had received antidepressant treatment and subsequently achieved clinical recovery and 34 matched controls.Results
Relative to the healthy controls, the treatment-naïve depressed patients showed increased white matter volumes in the left dorsolateral prefrontal cortex (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum posterior lobe and left inferior parietal lobule. For the treatment-naïve patients, the length in months of the current depressive episode was positively correlated with the white matter volumes in both the left DLPFC and left putamen. In the recovered patients, the differences in white matter volume were no longer statistically significant relative to healthy controls. No significant difference was found in the total white matter volume among the three groups.Conclusions
This study demonstrates that there were alterations in the white matter volumes of depressed patients, which might disrupt the neural circuits that are involved in emotional and cognitive function and thus contribute to the pathophysiology of depression. The finding of the significant correlations between refractoriness and the white matter volumes in the left DLPFC and left putamen combined with the finding that antidepressant treatment normalized the white matter volume of recovered patients, suggests that a quantitative, structural MRI measurement could act as a potential biomarker in depression therapy for individual subjects. 相似文献932.
Bin Wu Alisa Wilson Fang-fang Wang Su-li Wang Daniel J. Wallace Michael H. Weisman Liang-jing Lu 《PloS one》2012,7(10)
Background
To analyse the cost-effectiveness of traditional disease-modifying anti-rheumatic drugs (tDMARDs) compared to biological therapies from the perspective of Chinese society.Methodology/Principal Findings
A mathematical model was developed by incorporating the clinical trial data and Chinese unit costs and treatment sequences from a lifetime perspective. Hypothetical cohorts with moderate to severe RA were simulated. The primary outcome measure–quality-adjusted life years (QALYs)–was derived from disease severity (HAQ scores). Primary analysis included drug costs, monitoring costs, and other costs. Probabilistic and one-way sensitivity analyses were performed. Treatment sequences that included TNF antagonists and rituximab produced a greater number of QALYs than tDMARDs alone or TNF antagonists plus DMARDs. In comparison with tDMARDs, the incremental cost-effectiveness ratios (ICERs) for etanercept, infliximab, and adalimumab without rituximab were $77,357.7, $26,562.4 and $57,838.4 per QALY and $66,422.9, $28,780.6 and $50,937.6 per QALY, for etanercept, infliximab, and adalimumab with rituximab. No biotherapy was cost-effective under the willingness to pay threshold when the threshold was 3 times the per capita GDP of China. When 3 times the per capita GDP of Shanghai used as the threshold, infliximab and rituximab could yield nearly 90% cost-effective simulations in probabilistic sensitivity analysis.Conclusions/Significance
tDMARD was the most cost-effective option in the Chinese healthcare setting. In some relatively developed regions in China, infliximab and rituximab may be a favorable cost-effective alternative for moderate to severe RA. 相似文献933.
Metagenomic insights into the fibrolytic microbiome in yak rumen 总被引:1,自引:0,他引:1
X Dai Y Zhu Y Luo L Song D Liu L Liu F Chen M Wang J Li X Zeng Z Dong S Hu L Li J Xu L Huang X Dong 《PloS one》2012,7(7):e40430
The rumen hosts one of the most efficient microbial systems for degrading plant cell walls, yet the predominant cellulolytic proteins and fibrolytic mechanism(s) remain elusive. Here we investigated the cellulolytic microbiome of the yak rumen by using a combination of metagenome-based and bacterial artificial chromosome (BAC)-based functional screening approaches. Totally 223 fibrolytic BAC clones were pyrosequenced and 10,070 ORFs were identified. Among them 150 were annotated as the glycoside hydrolase (GH) genes for fibrolytic proteins, and the majority (69%) of them were clustered or linked with genes encoding related functions. Among the 35 fibrolytic contigs of >10 Kb in length, 25 were derived from Bacteroidetes and four from Firmicutes. Coverage analysis indicated that the fibrolytic genes on most Bacteroidetes-contigs were abundantly represented in the metagenomic sequences, and they were frequently linked with genes encoding SusC/SusD-type outer-membrane proteins. GH5, GH9, and GH10 cellulase/hemicellulase genes were predominant, but no GH48 exocellulase gene was found. Most (85%) of the cellulase and hemicellulase proteins possessed a signal peptide; only a few carried carbohydrate-binding modules, and no cellulosomal domains were detected. These findings suggest that the SucC/SucD-involving mechanism, instead of one based on cellulosomes or the free-enzyme system, serves a major role in lignocellulose degradation in yak rumen. Genes encoding an endoglucanase of a novel GH5 subfamily occurred frequently in the metagenome, and the recombinant proteins encoded by the genes displayed moderate Avicelase in addition to endoglucanase activities, suggesting their important contribution to lignocellulose degradation in the exocellulase-scarce rumen. 相似文献
934.
935.
Astrocytes participate in brain functions through Ca2+ signals, including Ca2+ waves and Ca2+ oscillations. Currently the mechanisms of Ca2+ signals in astrocytes are not fully clear. Here, we present a computational model to specify the relative contributions of different Ca2+ flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca2+ oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca2+ waves (CSDCWs) in a one-dimensional astrocyte network. This model shows that CASs depend primarily on Ca2+ released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca2+ influx. It predicts that voltage-gated Ca2+ influx is able to generate Ca2+ waves during the process of CSD even after depleting internal Ca2+ stores. Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs. This work quantitatively analyzes the generation of astrocytic Ca2+ signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs. Research on the different types of Ca2+ signals might help to understand the ways by which astrocytes participate in information processing in brain functions. 相似文献
936.
Ruicheng Wei Chunfu Yang Mei Zeng Frances Terry Kai Zhu Chunhui Yang Ralf Altmeyer William Martin Anne S. De Groot Qibin Leng 《PloS one》2012,7(12)
CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD), has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine. 相似文献
937.
PAC1 is PACAP (pituitary adenylate cyclase-activating polypeptide) preferring receptor belonging to class B G protein coupled receptor (GPCR) mediating the most effects of PACAP. The important role of G protein coupled receptor homo/heteromerization in receptor folding, maturation, trafficking, and cell surface expression has become increasingly evident. The bimolecular fluorescence complementation (BiFC) and bioluminescence resonance energy transfer (BRET) assay were used in this research to confirm the dimerization of PAC1 for the first time. The structure-activity relationship focused on the N-terminal HSDCIF motif, which locates behind the signal sequence and has high homology with PACAP (1–6), was assayed using a receptor mutant with the deletion of the HSDCIF motif. The fluorescence confocal microscope observation showed that the deletion of the HSDCIF motif impaired the cell delivery of PAC1. The results of BiFC, BRET and westernblot indicated that the deletion of HSDCIF motif and the replacement of the Cys residue with Ala in HSDCIF motif resulted in the disruption of receptor dimerization. And the exogenous chemically synthesized oligopeptide HSDCIF (100 nmol/L) not only down-regulated the dimerization of PAC1, induced the internalization of PAC1, but also inhibited the proliferation of CHO cells expressing PAC1 stably and decreased the activity of PACAP on the cell viability. All these data suggested that the N-terminal HSDCIF motif played key role in the trafficking and the dimerization of PAC1, and the exogenous oligopeptide HSDCIF had effects on the cell signaling, trafficking and the dimerization of PAC1. 相似文献
938.
Background
Matrix metalloproteinase-2 (MMP-2) is a key regulator in the migration of tumor cells. αvβ3 integrin has been reported to play a critical role in cell adhesion and regulate the migration of tumor cells by promoting MMP-2 activation. However, little is known about the effects of MMP-2 on αvβ3 integrin activity and αvβ3 integrin-mediated adhesion and migration of tumor cells.Methodology/Principal Findings
Human melanoma cells were seeded using an agarose drop model and/or subjected to in vitro analysis using immunofluorescence, adhesion, migration and invasion assays to investigate the relationship between active MMP-2 and αvβ3 integrin during the adhesion and migration of the tumor cells. We found that MMP-2 was localized at the leading edge of spreading cells before αvβ3 integrin. αvβ3 integrin-mediated adhesion and migration of the tumor cells were inhibited by a MMP-2 inhibitor. MMP-2 cleaved fibronectin into small fragments, which promoted the adhesion and migration of the tumor cells.Conclusion/Significance
MMP-2 cleaves fibronectin into small fragments to enhance the adhesion and migration of human melanoma cells mediated by αvβ3 integrin. These results indicate that MMP-2 may guide the direction of the tumor cell migration. 相似文献939.
Xin Wei Rongsheng Wang Lirong Cao Nannan Yuan Juan Huang Weihua Qiao Wanxia Zhang Hanlai Zeng Qingwen Yang 《PloS one》2012,7(11)
China is rich of germplasm resources of common wild rice (Oryza rufipogon Griff.) and Asian cultivated rice (O. sativa L.) which consists of two subspecies, indica and japonica. Previous studies have shown that China is one of the domestication centers of O. sativa. However, the geographic origin and the domestication times of O. sativa in China are still under debate. To settle these disputes, six chloroplast loci and four mitochondrial loci were selected to examine the relationships between 50 accessions of Asian cultivated rice and 119 accessions of common wild rice from China based on DNA sequence analysis in the present study. The results indicated that Southern China is the genetic diversity center of O. rufipogon and it might be the primary domestication region of O. sativa. Molecular dating suggested that the two subspecies had diverged 0.1 million years ago, much earlier than the beginning of rice domestication. Genetic differentiations and phylogeography analyses indicated that indica was domesticated from tropical O. rufipogon while japonica was domesticated from O. rufipogon which located in higher latitude. These results provided molecular evidences for the hypotheses of (i) Southern China is the origin center of O. sativa in China and (ii) the two subspecies of O. sativa were domesticated multiple times. 相似文献
940.