Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8

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Platelet antithrombin deficiency: a new clinical entity.

A kindred with a history of multiple thromboses was studied for coagulant abnormalities. A deficiency of serum antithrombin III was found in approximately half of the 13 family members by either coagulant or immunologic assay. No clear relationship between antithrombin III deficiency and a history of thrombosis was present. Platelet antithrombin assays were also studied in the same subjects. Ten of the 13 members were deficient. None of the remaining three had a history of thrombosis. On the basis of these findings, the hypothesis is proposed that in some cases familial hypercoagulability may be due to a platelet antithrombin deficiency and that the serum antithrombin III deficiency in some cases is a secondary rather than a primary effect.     

MicroRNA-185 inhibits cell proliferation and induces cell apoptosis by targeting VEGFA directly in von Hippel-Lindau–inactivated clear cell renal cell carcinoma

ObjectivesThe von Hippel-Lindau (VHL) gene acts as a tumor suppressor in most clear cell renal cell carcinomas (ccRCCs). Tumor growth in ccRCCs relies on many factors that result from the loss of VHL. This study aims to identify new microRNAs with therapeutic potential for VHL-inactivated ccRCCs.Materials and methodsWe used 786O, A498 (VHL inactivated), and Caki-1 (VHL intact) ccRCC cell lines and 40 ccRCC samples and their adjacent nontumor tissues to measure the expression of microRNA-185 (miR-185) by real-time quantitative polymerase chain reaction. Overexpression or knockdown of VEGFA expression in renal cancer cells was fulfilled by transfecting expression plasmids or small interfering RNAs. Overexpression of miR-185 in ccRCC cell lines was fulfilled by transfecting chemically synthesized miR-185 mimics. The effects of miR-185 on ccRCC cell lines were detected by MTS assay, colony formation assay, and flow cytometric analysis.ResultsCompared with adjacent nontumor renal tissues, miR-185 expression levels decreased significantly in ccRCC tissues. The expression of miR-185 had a negative correlation with tumor size, Fuhrman grade, and TNM staging. Luciferase assay showed that VEGFA was a direct target gene of miR-185. The overexpression of miR-185 significantly inhibited cell proliferation and induced cell apoptosis by down-regulating VEGFA expression in VHL-inactivated ccRCC cells.ConclusionsOur results suggest that the miR-185, as a tumor suppressor, plays a pivotal role by inhibiting VEGFA in VHL-inactivated ccRCC.     

Battlefield acupuncture to treat low back pain in the emergency department

Introduction

Battlefield acupuncture (BFA) is an ear acupuncture protocol used by the military for immediate pain relief. This is a pilot feasibility study of BFA as a treatment for acute low back pain (LBP) in the emergency department (ED).

Imaging genetics of schizophrenia

Recent years have seen an explosive growth of interest in the application of imaging genetics to understand neurogenetic mechanisms of schizophrenia. Imaging genetics applies structural and functional neuroimaging to study subjects carrying genetic risk variants that relate to a psychiatric disorder. We review selected aspects of this literature, starting with a widely studied candidate gene--the catechol-O-methyltransferase gene (COMT)--discussing other candidate genes in the dopaminergic system, and then discussing variants with genome-wide support. In future perspectives, approaches to characterize epistatic effects, the identification of new risk genes through forward-genetic approaches using imaging phenotypes, and the study of rare structural variants are considered.     

中国汉族高度近视一家系的ZNF644基因突变分析

目的：ZNF644基因突变被报道与一个中国汉族（四川）高度近视家系的性状相关,本研究旨在探索ZNF644基因与另一个中国汉族（湖南）高度近视家系的相关性。方法：收集家系中5例患者临床资料并采集5例患者及2例家系正常成员的外周血,提取基因组DNA,采用PCR扩增ZNF644基因的全部6个外显子及外显子与内含子交界区域,用直接双向测序、BLAST比对进行突变分析。结果：此家系中5例患者的近视屈光度均高于6．00D,同时部分患者伴发视网膜脱离、白内障等症状,家系其余成员视力正常,符合常染色体显性遗传模式的遗传性高度近视;在ZNF644基因中发现了6个变异序列,所有变异序列均存在于患者及其正常亲属中,与疾病表型无共分离现象。结论：排除了ZNF644基因外显子突变导致该家系高度近视的可能性。     

A Schizophrenia Risk Gene, ZNF804A, Influences Neuroanatomical and Neurocognitive Phenotypes

ZNF804A is one of the strongest candidate genes for schizophrenia (SZ), yet its function and role in disease pathophysiology are largely unknown. The only in vivo endophenotype study of the SZ-associated SNP (rs1344706) pointed towards effects on brain functional connectivity. We examined the relationship of this SNP to neuroanatomical and neurocognitive phenotypes that were assessed in healthy individuals. Volunteers with no history of psychiatric illness were assessed with structural magnetic resonance imaging (1.5T GE scanner, standard gradient-echo acquisition). Carriers of the minor allele were compared with homozygotes for the T (SZ-associated) allele on measures of total volume of the white matter (WM), gray matter (GM), and cerebrospinal fluid compartments, as well as on voxel-wise measurements of regional brain volumes. After examining the correlation between genotype-associated regions of interest and neurocognitive performance measures, the effects of rs1344706 genotype on a measure of visuomotor performance speed (trails A) were examined in an independent cohort of volunteers. Among healthy subjects, risk allele homozygotes showed larger total WM volumes than carriers of the other allele. Controlling for WM volumes, these same subjects showed reduced GM volumes in several regions comprising the ‘default mode network,'' including angular gyrus, parahippocampal gyrus, posterior cingulate, and medial orbitofrontal gyrus/gyrus rectus (FDR-corrected p<0.05). The risk allele dosage also predicted impairments on a timed visuomotor performance task (trails A). Results support a role of ZNF804A in phenotypes reflecting altered neural connectivity.