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81.
Xin-Tong Wei Gui-Juan Feng Hong Zhang Qian Xu Jing-Jing Ni Min Zhao Xiao-Lin Yang Qing Tian Hui Shen Rong Hai Hong-Wen Deng Lei Zhang Yu-Fang Pei 《European journal of human genetics : EJHG》2021,29(4):553
Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, :g.44956910G > A, discovery bivariate P = 4.83 × 10−9, replication P = 5.75 × 10−5) at the genome-wide significance level (ɑ = 5.0 × 10−8), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.Subject terms: NC_000017.11Genome-wide association studies, Gene expression profiling 相似文献
82.
Many studies have shown that genetic susceptibility plays a key role in determining whether bacterial pathogens successfully infect and cause disease in potential hosts. Surprisingly, whether host genetics influence the pathogenesis of attaching and effacing (A/E) bacteria such as enteropathogenic and enterohemorrhagic Escherichia coli has not been examined. To address this issue, we infected various mouse strains with Citrobacter rodentium, a member of the A/E pathogen family. Of the strains tested, the lipopolysaccharide (LPS) nonresponder C3H/HeJ mouse strain experienced more rapid and extensive bacterial colonization than did other strains. Moreover, the high bacterial load in these mice was associated with accelerated crypt hyperplasia, mucosal ulceration, and bleeding, together with very high mortality rates. Interestingly, the basis for the increased susceptibility was not due to LPS hyporesponsiveness, as the genetically related but LPS-responsive C3H/HeOuJ and C3H/HeN mouse strains were also susceptible to infection. Analysis of the intestinal pathology in these susceptible strains revealed significant crypt epithelial cell apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end label staining) as well as bacterial translocation to the mesenteric lymph nodes. Further studies with infection of SCID (T- and B-lymphocyte-deficient) C3H/HeJ mice demonstrated that loss of lymphocytes had no effect on bacterial numbers but did reduce crypt cell apoptosis and delayed mortality. These studies thus identify the adaptive immune system, crypt cell apoptosis, and bacterial translocation but not LPS responsiveness as contributing to the tissue pathology and mortality seen during C. rodentium infection of highly susceptible mouse strains. Determining the basis for these strains' susceptibility to intestinal colonization by an A/E pathogen will be the focus of future studies. 相似文献
83.
A CdtA-CdtC complex can block killing of HeLa cells by Haemophilus ducreyi cytolethal distending toxin 下载免费PDF全文
The cytolethal distending toxin (CDT) of Haemophilus ducreyi is comprised of the CdtA, CdtB, and CdtC proteins, with the CdtB protein having demonstrated enzymatic (i.e., DNase) activity. Using a single recombinant Escherichia coli strain with two plasmids individually containing the H. ducreyi cdtA and cdtC genes, we purified a noncovalent CdtA-CdtC complex. Incubation of this CdtA-CdtC complex with HeLa cells blocked killing of these cells by CDT holotoxin. Furthermore, the addition of purified recombinant CdtB to HeLa cells preincubated with the CdtA-CdtC complex resulted in the killing of these human epithelial cells. 相似文献
84.
应用细胞原位杂交技术,观察经重组小鼠白细胞介素-19(IL-1β)处理后的体外培养的新生1d大鼠中脑黑质神经元c-jun基因的表达.结果显示,培养的黑质细胞多为酪氨酸羟化酶阳性神经元,IL-1β可诱导体外培养的黑质神经元c-junmRNA表达,高水平的表达出现在IL-1β处理后2~4h。说明IL-1β有兴奋黑质神经元的作用,并提示黑质神经元上可能存在IL-1β受体. 相似文献
85.
Peng‐Yuan Liu Yue‐Juan Qin Robert R. Recker Hong‐Wen Deng 《American journal of human biology》2004,16(1):68-77
Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. In the present study, familial correlation and segregation analyses for the spine and hip bone sizes were performed for the first time in a Chinese sample composed of 393 nuclear families with a total of 1,193 individuals. The results indicate a major gene of codominant inheritance for spine bone size; however, there is no evidence of a major gene influencing hip bone size. Significant familial residual effects are found for both traits, suggesting their polygenic inheritance. Heritability estimates (±SE) for spine and hip bone size were 0.62 (0.13) and 0.59 (0.12), respectively. Sex and age differences in genotype‐specific average bone size were observed. Compared with our previous study on bone mineral density (BMD) in the same population, this study suggests that genetic determination of bone size may be different from that of BMD, and thus studying bone size as one surrogate phenotype for osteoporotic fractures may be necessary. Am. J. Hum. Biol. 16:68–77, 2004. © 2003 Wiley‐Liss, Inc. 相似文献
86.
目的:探讨血小板源性生长因子(PDGF)在低氧肺动脉高压血管构形重建发生中的作用。方法:应用免疫组化技术结合计算机图像分析,检测了低氧大鼠腺泡内肺动脉(IAPA)PDGF-B链蛋白表达水平。结果:常氧时,IAPA仅有PDGF-B链蛋白弱表达;低氧1天时,IAPA便有较强的PDGF-B链蛋白表达,定位于IAPA的内皮和中膜,低氧3天至14天仅分布于中膜;低氧1、3、5、7、14天各时间点PDGF-B链蛋白表达分别为常氧组的1.53、1.59、1.56、1.62和1.42倍,差异有显著性(P<0.01)。结论:PDGF-B链蛋白可能参与了低氧肺动脉高压血管构形重建的发病过程 相似文献
87.
人胚胎肺内神经内分泌细胞电镜观察 总被引:1,自引:0,他引:1
用透射电镜对不同胎龄的人胚胎肺内神经内分泌细胞进行了发生和超微结构观察。肺内支气管上皮内未分化细胞,第八周开始向神经内分泌细胞转化,提示神经内分泌细胞对早期胚胎肺的发生、发育有特殊意义。神经内分泌细胞内致密核心小泡(DCV)及其它与内分泌活动有关的各种细胞器发达。能见到P0细胞、P1细胞、P2细胞及P3细胞等四种类型的神经内分泌细胞。P0细胞的发生及分化程度表明它可能是一种前细胞,它可以进一步转化 相似文献
88.
Recombinant antibody cloning and phage display technologies were used to produce single-chain antibodies (scFv) against Clostridium difficile toxin B. The starting material was the mouse B cell hybridoma line 5A8, which generates a monoclonal antibody against the toxin. The integrated cloning, screening, and phage display system of Krebber et al. (J. Immunol. Methods 201:35-55, 1997) allowed us to rapidly obtain toxin B-binding scFv sequences derived from the hybridoma cell line. The best candidate scFv sequences, based on preliminary enzyme-linked immunosorbent assay (ELISA) screening data were then subcloned into the compatible expression vector. Recombinant single-chain antibodies were expressed in Escherichia coli. A 29-kDa band was observed on polyacrylamide gel electrophoresis as predicted. The expressed product was characterized by immunoblotting and detection with an anti-FLAG antibody. The toxin B-binding function of the single-chain antibody was shown by a sandwich ELISA. The antibody was highly specific for toxin B and did not cross-react with material isolated from a toxin B-negative C. difficile strain. The sensitivity of the soluble single-chain antibody is significantly higher than the original monoclonal antibody based on ELISA data and could detect a minimum of 10 ng of toxin B/well. Competitive ELISAs established that the affinity of the 5A8 parent antibody and the best representative (clone 10) of the single-chain antibodies were similar and in the range of 10(-8) M. We propose that recombinant antibody technology is a rapid and effective approach to the development of the next generation of immunodiagnostic reagents. 相似文献
89.
90.