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It is a long-standing question as to which genes define the characteristic facial features among different ethnic groups. In this study, we use Uyghurs, an ancient admixed population to query the genetic bases why Europeans and Han Chinese look different. Facial traits were analyzed based on high-dense 3D facial images; numerous biometric spaces were examined for divergent facial features between European and Han Chinese, ranging from inter-landmark distances to dense shape geometrics. Genome-wide association studies(GWAS) were conducted on a discovery panel of Uyghurs. Six significant loci were identified, four of which, rs1868752, rs118078182, rs60159418 at or near UBASH3B, COL23A1, PCDH7 and rs17868256 were replicated in independent cohorts of Uyghurs or Southern Han Chinese. A prospective model was also developed to predict 3D faces based on top GWAS signals and tested in hypothetic forensic scenarios.  相似文献   
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We test the hypothesis that pyranopterin (PPT) coordination plays a critical role in defining molybdenum active site redox chemistry and reactivity in the mononuclear molybdoenzymes. The molybdenum atom of Escherichia coli nitrate reductase A (NarGHI) is coordinated by two PPT-dithiolene chelates that are defined as proximal and distal based on their proximity to a [4Fe-4S] cluster known as FS0. We examined variants of two sets of residues involved in PPT coordination: (i) those interacting directly or indirectly with the pyran oxygen of the bicyclic distal PPT (NarG-Ser719, NarG-His1163, and NarG-His1184); and (ii) those involved in bridging the two PPTs and stabilizing the oxidation state of the proximal PPT (NarG-His1092 and NarG-His1098). A S719A variant has essentially no effect on the overall Mo(VI/IV) reduction potential, whereas the H1163A and H1184A variants elicit large effects (ΔEm values of −88 and −36 mV, respectively). Ala variants of His1092 and His1098 also elicit large ΔEm values of −143 and −101 mV, respectively. An Arg variant of His1092 elicits a small ΔEm of +18 mV on the Mo(VI/IV) reduction potential. There is a linear correlation between the molybdenum Em value and both enzyme activity and the ability to support anaerobic respiratory growth on nitrate. These data support a non-innocent role for the PPT moieties in controlling active site metal redox chemistry and catalysis.  相似文献   
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In order to identify the lower limb movements accurately and quickly, a recognition method based on extreme learning machine (ELM) is proposed. The recognizing target set is constructed by decomposing the daily actions into different segments. To get the recognition accuracy of seven movements based on the surface electromyography, the recognition feature vector space is established by integrating short-time statistical characteristics under time domain, and locally linear embedding algorithm is used to reduce the computational complexity and improve robustness of algorithm. Compared with BP, the overall recognition accuracy for each subject in the best dimension with ELM is above 95%.  相似文献   
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Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n = 60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment.  相似文献   
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Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.  相似文献   
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Polyomavirus BK (BKV) infection is an important cause of renal allograft failure. Viral microRNAs are known to play a crucial role in viral replication. This study investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with polyomavirus-associated nephropathy (PVAN) and their role in viral replication. Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1 levels were significantly increased. Cells transfected with the vector containing the miR-B1 precursor (the miR-B1 vector) showed a significant increase in expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with the miR-B1-mutated vector. Transfection of the miR-B1 expression vector or the 3p and 5p miR-B1 oligonucleotides inhibited expression of TAg. TAg-enhanced promoter activity and BKV replication were inhibited by miR-B1. In contrast, inhibition of miR-B1 expression by addition of miR-B1 antagomirs or silencing of Dicer upregulated the expression of TAg and VP1 proteins in BKV-infected cells. Importantly, patients with PVAN had significantly higher levels of 3p and 5p miR-B1 compared to renal transplant patients without PVAN. In conclusion, we demonstrated that (1) miR-B1 expression was upregulated during BKV infection and (2) miR-B1 suppressed TAg-mediated autoregulation of BKV replication. Use of miR-B1 can be evaluated as a potential treatment strategy against BKV infection.  相似文献   
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