不同时期北部湾日本带鱼营养生态位差异

基于2008-2009年和2018年对北部湾 日本带鱼的采样,通过测定碳氮稳定同位素,计算其营养级、营养生态位等指标,对比分析10年前后日本带鱼营养生态位的差异,探究其生态适应能力的变动.结果表明:2个时期北部湾日本带鱼碳稳定同位素(δ13C)值差异明显,2018年δ13C值范围变窄,平均值变小,推测 日本带鱼食物来源...     

Extracellular High Mobility Group Box-1 (HMGB1) Inhibits Enterocyte Migration via Activation of Toll-like Receptor-4 and Increased Cell-Matrix Adhesiveness

Toll-like receptor-4 (TLR4) is the receptor for bacterial lipopolysaccharide, yet it may also respond to a variety of endogenous molecules. Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in newborn infants and is characterized by intestinal mucosal destruction and impaired enterocyte migration due to increased TLR4 signaling on enterocytes. The endogenous ligands for TLR4 that lead to impaired enterocyte migration remain unknown. High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. We thus hypothesize that extracellular HMGB1 inhibits enterocyte migration via activation of TLR4 and sought to define the pathways involved. We now demonstrate that murine and human NEC are associated with increased intestinal HMGB1 expression, that serum HMGB1 is increased in murine NEC, and that HMGB1 inhibits enterocyte migration in vitro and in vivo in a TLR4-dependent manner. This finding was unique to enterocytes as HMGB1 enhanced migration of inflammatory cells in vitro and in vivo. In seeking to understand the mechanisms involved, TLR4-dependent HMGB1 signaling increased RhoA activation in enterocytes, increased phosphorylation of focal adhesion kinase, and increased phosphorylation of cofilin, resulting in increased stress fibers and focal adhesions. Using single cell force traction microscopy, the net effect of HMGB1 signaling was a TLR4-dependent increase in cell force adhesion, accounting for the impaired enterocyte migration. These findings demonstrate a novel pathway by which TLR4 activation by HMGB1 delays mucosal repair and suggest a novel potential therapeutic target in the amelioration of intestinal inflammatory diseases like NEC.     

LPA induces osteoblast differentiation through interplay of two receptors: LPA1 and LPA4

The bioactive phospholipid, lysophosphatidic acid (LPA), acting through at least five distinct receptors LPA1–LPA5, plays important roles in numerous biological processes. Here we report that LPA induces osteoblastic differentiation of human mesenchymal stem cells hMSC‐TERT. We find that hMSC‐TERT mostly express two LPA receptors, LPA1 and LPA4, and undergo osteoblastic differentiation in serum‐containing medium. Inhibition of LPA1 with Ki16425 completely abrogates osteogenesis, indicating that this process is mediated by LPA in the serum through activation of LPA1. In contrast to LPA1, down‐regulation of LPA4 expression with shRNA significantly increases osteogenesis, suggesting that this receptor normally exerts negative effects on differentiation. Mechanistically, we find that in hMSC‐TERT, LPA induces a rise in both cAMP and Ca²⁺. The rise in Ca²⁺ is completely abolished by Ki16425, whereas LPA‐mediated cAMP increase is not sensitive to Ki16425. To test if LPA signaling pathways controlling osteogenesis in vitro translate into animal physiology, we evaluated the bones of LPA4‐deficient mice. Consistent with the ability of LPA4 to inhibit osteoblastic differentiation of stem cells, LPA4‐deficient mice have increased trabecular bone volume, number, and thickness. J. Cell. Biochem. 109: 794–800, 2010. © 2010 Wiley‐Liss, Inc.     

随机SNP在全基因组关联研究人群分层分析中的应用

在复杂疾病的全基因组关联研究中,人群分层现象会增加结果的假阳性率,因此考虑人群遗传结构、控制人群分层是很有必要的。而在人群分层研究中,使用随机选择的SNP的效果还有待进一步探讨。文章利用HapMap Phase2人群中无关个体的Affymetrix SNP 6.0芯片分型数据,在全基因组上随机均匀选择不同数量的SNP,同时利用f值和Fisher精确检验方法筛选祖先信息标记（Ancestry Informative Markers,AIMs）。然后利用HapMap Phase3中的无关个体的数据,以F-statistics和STRUCTURE分析两种方法评估所选出的不同SNP组合对人群的区分效果。研究发现,随机均匀分布于全基因组的SNP可用于识别人群内部存在的遗传结构。文章进一步提示,在全基因组关联研究中,当没有针对特定人群的AIMs时,可在全基因组上随机选择3000以上均匀分布的SNP来控制人群分层。     

TGF-α、TGF-β1在胰腺癌中的表达及临床意义

目的:研究TGF-α、TGF-β1与胰腺癌临床病理的关系.方法:免疫组织化学SABC法检测41例胰腺癌组织和12例正常胰腺组织中TGF-α、TGF-β1的表达情况,并分析其与病人的年龄、性别、肿瘤部位、病理分级和分期(UICC)等指标的相关性.结果:在41例胰腺癌组织中TGF-αTGF-β1的阳性表达率分别为73.2%、63.4%,在12例正常胰腺组织中的阳性表达率分别为16.7%、25.0%,两组之间存在显著差异(P=0.001).在胰腺癌组织中,TGF-β1的表达在不同分期中存在显著差异(P=0.019);TGF-α的表达与胰腺癌患者的年龄、性别、肿瘤部位、大小、分期及组织学分级无相关性(P>0.05).结论:TGF-α、TGF-β1在胰腺癌中高表达.TGF-β1与胰腺癌病理分期有关.     

Moderate Alcohol Use and Cardiovascular Disease from Mendelian Randomization

Background

Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use.

Methods

We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study.

Results

ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45).

Conclusion

Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.     

尾叶桉人工林生物量和生产力的研究

按径级标准木法测定了尾叶桉（Ｅｕｃａｌｙｐｔｕｓ ｕｒｏｐｈｙｌｌａ）器官生物量,建立了林木器官干重（ｗ）与胸径和树高（Ｄ＾３Ｈ）关系的相对生长方程,进而计算出尾叶桉林分的生物量和生产力。结果表明：东门林场１０年生尾叶桉人工林平均生物量为１４４．８５ｔ ｈｍ＾２,各器官生物量的在小序列为：干材（７１．６９％）〉根（１４．２１％）〉皮）７．９９％）〉枝（４．７１％）〉叶（４．７１％）〉叶（１．４０％     

Syphilis Screening among 27,150 Pregnant Women in South Chinese Rural Areas Using Point-of-Care Tests

Objectives

To determine the prevalence and correlates of syphilis among pregnant women in rural areas of South China.

Methods

Point-of-care syphilis testing was provided at 71 health facilities in less developed, rural areas of Guangdong Province. Positive samples were confirmed at a local referral center by toluidine red unheated serum tests (TRUST) and Treponema pallidum particle agglutination (TPPA) tests.

Results

Altogether 27,150 pregnant women in rural Guangdong were screened for syphilis. 106 (0.39%) syphilis cases were diagnosed, of which 78 (73.6%) received treatment for syphilis. Multivariate analysis revealed that older pregnant women (31–35 years old, aOR 2.7, 95% CI 0.99–7.32; older than 35 years old, aOR 5.9, 95% CI 2.13–16.34) and those with a history of adverse pregnant outcomes (aOR 3.64, 95% CI 2.30–5.76) were more likely to be infected with syphilis.

Conclusions

A high prevalence of syphilis exists among pregnant women living in rural areas of South China. Enhanced integration of syphilis screening with other routine women''s health services (OB GYN, family planning) may be useful for controlling China''s syphilis epidemic.     

Ser84是spindlin1定位与功能发挥的关键位点

spindlin1为作者所在研究组克隆并命名的肿瘤相关新基因,之前研究表明spindlin1蛋白定位于细胞核,并有可能通过对TCF-4通路的调节参与对肿瘤细胞生长和周期的调控．为进一步探索spindlin1的作用机制,明确spindlin1结构与功能的关系,在生物信息学分析及晶体结构解析的基础上,构建系列突变表达载体,首先以spindlin1蛋白亚细胞定位为指标,观察野生型及系列突变体spindlin1蛋白的亚细胞定位,并进一步检测野生型及突变体spindlin1对TCF-4荧光素酶报告基因转录活性的调控作用,以明确spindlin1定位与功能的关键位点．结果表明：Ser14＋Ser84、Ser84＋Ser99、Ser14＋Ser84＋Ser99位点Ser到Ala的联合突变能使野生型融合蛋白在细胞核内集中分布的特性消失,成为全细胞弥散分布,而Ser14、Ser84、Ser99各位点的单独突变或Ser14＋Ser99联合突变对spindlin1蛋白的细胞核内分布没有影响．与此同时,对TCF-4荧光素酶报告基因活性的分析表明,Ser14＋Ser84、Ser84＋Ser99、Ser14＋Ser84＋Ser99的联合突变使spindlin1对其活性的激活作用消失或降低．上述结果表明,Ser84是spindlin1细胞定位与功能发挥的关键位点,其作用发挥需要Ser14与Ser99的协助．