c—fos,c—myb和c—erbB—2与大鼠卵巢颗粒细胞生孕酮调？…

目的和方法：用离体细胞体外孵育法,观察肥义ｃ－ｆｏｓ、ｃ－ｍｙｂ和ｃ－ｅｒｂＢ－２寡脱氧核苷酸（ｃ－ｆｏｓ ＯＤＮ、ｃ－ｍｙｂ ＯＤＮ和ｃ－ｅｒｂＢ－２ ＯＤＮ）对ｈＣＧ诱导大鼠颗粒细胞孕酮产生的影响。同时观察内皮素－１、γ－氨基丁酸和钙离子通道阻断剂维拉帕米对细胞中ｃ－ｆｏｓ、ｃ－ｍｙｂ和ｃ－ｅｒｂＢ－２蛋白的影响。结果：反义ｃ－ｆｏｓ、ｃ－ｍｙｂ和ｃ－ｅｒｂＢ－２ ＯＤＮ均明显抑制ｈＣＧ诱导颗     

Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries

BackgroundTaller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke.Methods and findingsHeight-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations.ConclusionsThe findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.

In a Mendelian randomization study, Andrew B. Linden and colleagues study the relationship between height and risk of stroke subtypes among individuals from the MEGASTROKE consortium, China Kadoorie Biobank, and UK Biobank.     

藻－菌生态系统代谢功能的生态学研究

在室内模拟条件下,研究了一些生态因子对藻－菌（Ａ＋Ｂ）生态系统代谢有机碳（Ｃ６Ｈ１２Ｏ６）、ＮＨ３－Ｎ和无机磷（ＩＰ）的影响．研究结果表明,当藻－菌生态系统中藻（Ａ）或菌（Ｂ）的起始数量一定时,其代谢Ｃ６Ｈ１２Ｏ６的速率,随与之组合的Ｂ或Ａ的起始数量增加（数量比则相应降低）而增加．在光照和黑暗条件下,Ａ＋Ｂ系统代谢上述３种营养物质的速率均有一定的差异．黑暗下Ｃ６Ｈ１２Ｏ６的平均代谢速率较光照下高１２．３％（Ｐ＜０．０５）,ＩＰ和ＮＨ３－Ｎ的平均代谢速率则分别较光照下低１４．４％（Ｐ＜０．０５）和１６．２％（Ｐ＜０．００１）．在Ａ＋Ｂ系统和Ａ、Ｂ单培养物中,３种营养物质的代谢速率均随有机负荷量增加而增加,而且Ａ＋Ｂ系统的代谢速率分别高于单培养的Ａ和Ｂ,其中ＮＨ３－Ｎ代谢尤为显著．文章还就生态系统结构与功能的关系问题进行了讨论．     

显微注射法制备遗传工程小鼠模型的研究

遗传工程小鼠模型是基因功能、人类疾病发病机制及新药研究开发的最重要的模式生物之一。在建立遗传工程小鼠模型的众多方法中,显微注射法是目前国际上公认的制备转基因及基因剔除动物模型的首选。在进行了大量显微注射工作后,简要介绍建立遗传工程小鼠模型的基本技术与方法,并对在显微操作过程中较为关键的因素进行一些分析和讨论。     

A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is mediated by its stable interaction with Rad5

DNA damage tolerance consisting of template switching and translesion synthesis is a major cellular mechanism in response to unrepaired DNA lesions during replication. The Rev1 pathway constitutes the major mechanism of translesion synthesis and base damage-induced mutagenesis in model cell systems. Rev1 is a dCMP transferase, but additionally plays non-catalytic functions in translesion synthesis. Using the yeast model system, we attempted to gain further insights into the non-catalytic functions of Rev1. Rev1 stably interacts with Rad5 (a central component of the template switching pathway) via the C-terminal region of Rev1 and the N-terminal region of Rad5. Supporting functional significance of this interaction, both the Rev1 pathway and Rad5 are required for translesion synthesis and mutagenesis of 1,N⁶-ethenoadenine. Furthermore, disrupting the Rev1–Rad5 interaction by mutating Rev1 did not affect its dCMP transferase, but led to inactivation of the Rev1 non-catalytic function in translesion synthesis of UV-induced DNA damage. Deletion analysis revealed that the C-terminal 21-amino acid sequence of Rev1 is uniquely required for its interaction with Rad5 and is essential for its non-catalytic function. Deletion analysis additionally implicated a C-terminal region of Rev1 in its negative regulation. These results show that a non-catalytic function of Rev1 in translesion synthesis and mutagenesis is mediated by its interaction with Rad5.     

Extracellular Alix regulates integrin-mediated cell adhesions and extracellular matrix assembly

Alix (ALG-2-interacting protein X), a cytoplasmic adaptor protein involved in endosomal sorting and actin cytoskeleton assembly, is required for the maintenance of fibroblast morphology. As Alix has sequence similarity to adhesin in Entamoeba histolytica, and we observed that Alix is secreted, we determined whether extracellular Alix affects fibroblast morphology. Here, we demonstrate that secreted Alix is deposited on the substratum of non-immortalized WI38 fibroblasts. Antibody binding to extracellular Alix retards WI38 cell adhesion and spreading on fibronectin and vitronectin. Alix knockdown in WI38 cells reduces spreading and fibronectin assembly, and the effect is partially complemented by coating recombinant Alix on the cell substratum. Immortalized NIH/3T3 fibroblasts deposit less Alix on the substratum and have defects in α₅β₁-integrin functions. Coating recombinant Alix on the culture substratum for NIH/3T3 cells promotes α₅β₁-integrin-mediated cell adhesions and fibronectin assembly, and these effects require the aa 605–709 region of Alix. These findings demonstrate that a sub-population of Alix localizes extracellularly and regulates integrin-mediated cell adhesions and fibronectin matrix assembly.     

萝藦科马利筋族植物化学成分研究进展(Ⅱ)

综述了到目前为止,从马利筋族植物中发现的黄酮、强心甙、生物碱、萜类、苯衍生物类等成分的种类及其分布,并介绍了一些化合物的药理作用以及黄酮类和C21甾体化合物在鹅绒藤属化学分类中的作用.     

Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection

Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease in infected mice which has similarities to multiple sclerosis. Spleen cells from TMEV-infected SJL/J mice stimulated with antigen-presenting cells infected with TMEV resulted in a population of autoreactive CD8+ cytotoxic T cells that kill uninfected syngeneic cells. We established CD8+ T cell clones that could kill both TMEV-infected and uninfected syngeneic targets, although infected target cells were killed more efficiently. The CD8+ T-cell clones produced gamma interferon when incubated with either infected or uninfected syngeneic target cells. Intracerebral injection of the clones into na?ve mice induced degeneration, not only in the brain, but also in the spinal cord. This suggests that CD8+ Tc1 cells could play a pathogenic role in central nervous system inflammation.