Circle of Willis variation in a complex stroke presentation: a case report

Background  

The impact of circle of Willis anatomical variation upon the presentation of stroke is probably underrecognised.     

利用重组自交系群体对黄瓜侧枝相关性状进行QTL定位分析

侧枝与黄瓜(Cucumis sativus)产量有密切关系. 本实验利用侧枝长势较弱、萌发较早的华北类型品系S94和侧枝长势较强、萌发较晚的欧洲类型品系S06构建的224个F6:7家系进行黄瓜侧枝相关性状的研究. 利用已构建的重组自交系群体遗传图谱, 使用软件WinQTLCart 2.5进行复合区间定位. 在2006年秋和2007年春两季, 共检测到4个侧枝相关性状(侧枝均长LBAL、侧枝总长LBTL、侧枝数目LBN和第一侧枝节位FLBN)的36个QTL, 单个QTL的贡献率在3.1%(lbtl2.1, 春季)~32.3%(lbn2.3, 春季)之间. 结果显示, 4个不同性状的11个QTL (lbal1.1, lbtl1.1, lbn1.2, flbn1.2等)在两季中都聚集在第1连锁群e23m18d~ME23EM6c之间(7.4 cM), 并且在第2连锁群的S94A1~ME4SA4a之间(13.9 cM)也检测到了4个不同性状的15个QTL (lbal2.1, lbtl2.1, lbn2.1和flbn2.1等). 两季共有21个QTL贡献率超过10%, 其中lbn2.3的贡献率(春季32.3%, LOD=18.4)为最大, lbtl1.3(秋季26.2%, LOD=17.4; 春季26.9%, LOD=17.9)在两季的位置和贡献率都稳定. 这些基因座为将来进行QTL精细定位提供了参考, 同时利用其紧密连锁(<10 cM)的特异标记(CMBR40, F, CS30, S94A1, CSWTA11B)可进行黄瓜侧枝性状的分子标记辅助育种.     

Genetic Diversity of Global Aromatic Rice Varieties

Genetic diversity of 434 rice accessions collected from 16 countries, including 345 fragrance rice varieties and 89 non fragrance rice varieties, have been analyzed. A total of 573 alleles were detected by using 77 simple sequence repeats (SSR) primer pairs covering all rice 12 chromosomes. The value of allelic polymorphism information content (PIC) ranged from 0090 to 0845, with an average of 0516 per locus; Gene diversity (GD) varied from 0091 to 0859, with an average of 0573; The mean value of major allele frequencies (MAF) was 0540, covering from 0251 to 0953. In addition, 434 rice accessions are divided into three sub populations by cluster and population structure analysis, and FST between sub populations showed a mean of -0116, ranging from -0623 to 0494; The score of genetic distance calculated by Nei′s method appeared from 0207 to 0355. Major allele frequencies within each sub population distributed from 0408 to 0746, and gene diversity level from 0354 to 0699, while PIC from 0320 to 0658. Sequencing 6 mitochondrion genes in 18 rice varieties exhibited no different in 5 genes, whereas Mit4 contains a 3 SNPs in the gene body, which acts as an important marker to understanding the relationship between Indica/Japonica differentiation and the evolution of fragrant gene. Finally, genetic diversity and mitochondrion gene sequencing would help to know about the origin of fragrant resource and benefit rice breeding.     

Toll‐like receptor 9 protects non‐immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2

Toll‐like receptor 9 (TLR9) has a key role in the recognition of pathogen DNA in the context of infection and cellular DNA that is released from damaged cells. Pro‐inflammatory TLR9 signalling pathways in immune cells have been well investigated, but we have recently discovered an alternative pathway in which TLR9 temporarily reduces energy substrates to induce cellular protection from stress in cardiomyocytes and neurons. However, the mechanism by which TLR9 stimulation reduces energy substrates remained unknown. Here, we identify the calcium‐transporting ATPase, SERCA2 (also known as Atp2a2), as a key molecule for the alternative TLR9 signalling pathway. TLR9 stimulation reduces SERCA2 activity, modulating Ca²⁺ handling between the SR/ER and mitochondria, which leads to a decrease in mitochondrial ATP levels and the activation of cellular protective machinery. These findings reveal how distinct innate responses can be elicited in immune and non‐immune cells—including cardiomyocytes—using the same ligand‐receptor system.     

Wistar大鼠幼年期丰富环境刺激对其社会竞争行为的影响

目的：探讨大鼠幼年期丰富环境经历对其成年后焦虑样行为和社会竞争行为的影响。方法：幼年期Wistar大鼠（生后21天）分为标准饲养组（对照组）和丰富环境刺激（EE）组。对照组为持续在标准实验室饲养条件下饲养;丰富环境组为生后21天至行为学检查时持续在丰富环境下饲养。在生后70天进行行为学检测：采用高架十字迷宫方法测试焦虑样行为;采用社会优势管道试验观察社会竞争性行为。结果：高架十字迷宫实验结果显示,与对照组相比,丰富环境组在开放臂的时间和次数显著增加;优势管道实验结果显示丰富环境刺激组大鼠的社会竞争力明显下降。结论：大鼠幼年期丰富环境刺激可改善大鼠的焦虑样情绪,但导致大鼠社会竞争力下降。     

C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1-selective binding of this fusion protein, granulocytes acquire additional TRAIL-mediated cytotoxic activity that, importantly, potentiates antibody-mediated cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab, cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the clinical potential of anticancer antibody therapy by augmenting tumoricidal activity of granulocytes.     

非酒精性脂肪肝病大鼠肝脏SOCS-3的表达与吡格列酮干预研究

目的：探讨SOCS-3在非酒精性脂肪肝病（NAFLD）发病中的作用以及吡格列酮的干预作用。方法：29只雄性SD大鼠随机分为正常对照组（8只）,高脂饮食组（21只）。饲养8周后,从高质饮食组随机抽取5只大鼠证实造模成功后,将该组余下的16只大鼠继续以高脂饲料喂养,并随机分为NAFLD对照组（8只）;吡格酮干预组（8只）,予以吡格列酮3mg·kg^-1·d^-1灌胃。16周末,处死所有大鼠,检测血糖、血胰岛素、血脂、肝脏SOCS-3mRNA和SREBP-lcmRNA表达及肝脏病理学。结果：与正常对照组相比,NAFLD组血糖、血胰岛素、血脂、肝脏脂肪变水平及肝组织SOCS-3mRNA、SREBPlCmRNA表达显著上调。吡格列酮干预组sOCS．3mRNA、SREBP-1cmRNA表达较NAFLD组下调,且血糖、血胰岛素、血脂、肝脏脂肪变水平下降。SOCS-3mRNA表达水平与胰岛素抵抗指数、SREBP．1cmRNA表达水平、肝脂肪变成显著正相关。结论：SOCS-3可能通过胰岛素抵抗及上调肝组织SREBP-lcmRNA表达参与NAFLD发病,吡格列酮能抑制肝脏SOCS-3的表达,对NAFLD有一定治疗作用。     

Studies on proinsulin and proglucagon biosynthesis and conversion at the subcellular level: I. Fractionation procedure and characterization of the subcellular fractions

Anglerfish islets were homogenized in 0.25 M sucrose and separated into seven separate subcellular fractions by differential and discontinuous density gradient centrifugation. The objective was to isolate microsomes and secretory granules in a highly purified state. The fractions were characterized by electron microscopy and chemical analyses. Each fraction was assayed for its content of protein, RNA, DNA, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG). Ultrastructural examination showed that two of the seven subcellular fractions contain primarily mitochondria, and that two others consist almost exclusively of secretory granules. A fifth fraction contains rough and smooth microsomal vesicles. The remaining two fractions are the cell supernate and the nuclei and cell debris. The content of DNA and RNA in all fractions is consistent with the observed ultrastructure. More than 82 percent of the total cellular IRI and 89(percent) of the total cellular IRG are found in the fractions of secretory granules. The combined fractions of secretory granules and microsomes consistently yield >93 percent of the total IRG. These results indicate that the fractionation procedure employed yields fractions of microsomes and secretory granules that contain nearly all the immunoassayable insulin and glucagons found in whole islet tissue. These fractions are thus considered suitable for study of proinsulin and proglucagon biosynthesis and their metabolic conversion at the subcellular level.     

蜘蛛丝蛋白的模块结构性能和重组表达

蜘蛛丝是一类天然蛋白质纤维,具有独特的机械性能（高强度、高弹性和高断裂功等）和卓著的生物学特性（生物可降解性和与生物组织的相容性等）,在生物医学、材料、纺织和军事等领域都有着很高的潜在应用价值。综述了不同蜘蛛丝蛋白的模块结构特征及与其功能的关系,扼要介绍了目前利用各种基因工程方法表达重组蜘蛛丝蛋白的研究进展。     

Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses

Currently, two neuraminidase (NA) inhibitors, oseltamivir and zanamivir, which must be administrated twice daily for 5 days for maximum therapeutic effect, are licensed for the treatment of influenza. However, oseltamivir-resistant mutants of seasonal H1N1 and highly pathogenic H5N1 avian influenza A viruses have emerged. Therefore, alternative antiviral agents are needed. Recently, a new neuraminidase inhibitor, R-125489, and its prodrug, CS-8958, have been developed. CS-8958 functions as a long-acting NA inhibitor in vivo (mice) and is efficacious against seasonal influenza strains following a single intranasal dose. Here, we tested the efficacy of this compound against H5N1 influenza viruses, which have spread across several continents and caused epidemics with high morbidity and mortality. We demonstrated that R-125489 interferes with the NA activity of H5N1 viruses, including oseltamivir-resistant and different clade strains. A single dose of CS-8958 (1,500 µg/kg) given to mice 2 h post-infection with H5N1 influenza viruses produced a higher survival rate than did continuous five-day administration of oseltamivir (50 mg/kg twice daily). Virus titers in lungs and brain were substantially lower in infected mice treated with a single dose of CS-8958 than in those treated with the five-day course of oseltamivir. CS-8958 was also highly efficacious against highly pathogenic H5N1 influenza virus and oseltamivir-resistant variants. A single dose of CS-8958 given seven days prior to virus infection also protected mice against H5N1 virus lethal infection. To evaluate the improved efficacy of CS-8958 over oseltamivir, the binding stability of R-125489 to various subtypes of influenza virus was assessed and compared with that of other NA inhibitors. We found that R-125489 bound to NA more tightly than did any other NA inhibitor tested. Our results indicate that CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants.