LY2228820 Dimesylate,a Selective Inhibitor of p38 Mitogen-activated Protein Kinase,Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo

LY2228820 dimesylate is a highly selective small molecule inhibitor of p38α and p38β mitogen-activated protein kinases (MAPKs) that is currently under clinical investigation for human malignancies. p38 MAPK is implicated in a wide range of biological processes, in particular those that support tumorigenesis. One such process, angiogenesis, is required for tumor growth and metastasis, and many new cancer therapies are therefore directed against the tumor vasculature. Using an in vitro co-culture endothelial cord formation assay, a surrogate of angiogenesis, we investigated the role of p38 MAPK in growth factor- and tumor-driven angiogenesis using LY2228820 dimesylate treatment and by shRNA gene knockdown. p38 MAPK was activated in endothelial cells upon growth factor stimulation, with inhibition by LY2228820 dimesylate treatment causing a significant decrease in VEGF-, bFGF-, EGF-, and IL-6-induced endothelial cord formation and an even more dramatic decrease in tumor-driven cord formation. In addition to involvement in downstream cytokine signaling, p38 MAPK was important for VEGF, bFGF, EGF, IL-6, and other proangiogenic cytokine secretion in stromal and tumor cells. LY2228820 dimesylate results were substantiated using p38α MAPK-specific shRNA and shRNA against the downstream p38 MAPK effectors MAPKAPK-2 and HSP27. Using in vivo models of functional neoangiogenesis, LY2228820 dimesylate treatment reduced hemoglobin content in a plug assay and decreased VEGF-A-stimulated vascularization in a mouse ear model. Thus, p38α MAPK is implicated in tumor angiogenesis through direct tumoral effects and through reduction of proangiogenic cytokine secretion via the microenvironment.     

Differing Epidemiological Dynamics of Influenza B Virus Lineages in Guangzhou,Southern China, 2009-2010

The epidemiological and evolutionary dynamics of the two cocirculating lineages of influenza B virus, Victoria and Yamagata, are poorly understood, especially in tropical or subtropical areas of Southeast Asia. We performed a phylogenetic analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and compared the demographic and clinical features of infected patients. We identified multiple viral introductions of Victoria strains from both Chinese and international sources, which formed two phylogenetically and antigenically distinct clades (Victoria 1 and 2), some of which persisted between seasons. We identified one dominant Yamagata introduction from outside China during 2009. Our phylogenetic analysis reveals the occurrence of reassortment events among the Victoria and Yamagata lineages and also within the Victoria lineage. We found no significant difference in clinical severity by influenza B lineage, with the exceptions that (i) the Yamagata lineage infected older people than either Victoria lineage and (ii) fewer upper respiratory tract infections were caused by the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex epidemiological dynamics of different influenza B lineages within a single geographic locality and has implications for vaccination policy in southern China.     

Ontogeny of hypoxic modulation of cardiac performance and its allometry in the African clawed frog Xenopus laevis

The ontogeny of cardiac hypoxic responses, and how such responses may be modified by rearing environment, are poorly understood in amphibians. In this study, cardiac performance was investigated in Xenopus laevis from 2 to 25 days post-fertilization (dpf). Larvae were reared under either normoxia or moderate hypoxia (PO₂ = 110 mmHg), and each population was assessed in both normoxia and acute hypoxia. Heart rate (f _h ) of normoxic-reared larvae exhibited an early increase from 77 ± 1 beats min^?1 at 2 dpf to 153 ± 1 beats min^?1 at 4 dpf, followed by gradual decreases to 123 ± 3 beats min^?1 at 25 dpf. Stroke volume (SV), 6 ± 1 nl, and cardiac output (CO), 0.8 ± 0.1 μl min^?1, at 5 dpf both increased by more than 40-fold to 25 dpf with rapid larval growth (~30-fold increase in body mass). When exposed to acute hypoxia, normoxic-reared larvae increased f _h and CO between 5 and 25 dpf. Increased SV in acute hypoxia, produced by increased end-diastolic volume (EDV), only occurred before 10 dpf. Hypoxic-reared larvae showed decreased acute hypoxic responses of EDV, SV and CO at 7 and 10 dpf. Over the period of 2–25 dpf, cardiac scaling with mass showed scaling coefficients of ?0.04 (f _h ), 1.23 (SV) and 1.19 (CO), contrary to the cardiac scaling relationships described in birds and mammals. In addition, f _h scaling in hypoxic-reared larvae was altered to a shallower slope of ?0.01. Collectively, these results indicate that acute cardiac hypoxic responses develop before 5 dpf. Chronic hypoxia at a moderate level can not only modulate this cardiac reflex, but also changes cardiac scaling relationship with mass.     

(Z)-4-Bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one sensitizes Escherichia coli persister cells to antibiotics

Persisters are a small subpopulation of bacterial cells that are dormant and extremely tolerant to antibiotics. The intrinsic antibiotic tolerance of persisters also facilitates the development of multidrug resistance through acquired mechanisms based on drug resistance genes. In this study, we demonstrate that (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8) can reduce persistence during Escherichia coli growth and revert the antibiotic tolerance of its persister cells. The effects of BF8 were more profound when the pH was increased from 6 to 8.5. Although BF8 is a quorum sensing (QS) inhibitor, similar effects were observed for the wild-type E. coli RP437 and its ΔluxS mutant, suggesting that these effects did not occur solely through inhibition of AI-2-mediated QS. In addition to its effects on planktonic persisters, BF8 was also found to disperse RP437 biofilms and to render associated cells more sensitive to ofloxacin. At the doses that are effective against E. coli persister cells, BF8 appeared to be safe to the tested normal mammalian cells in vitro and exhibited no long-term cytotoxicity to normal mouse tissues in vivo. These findings broadened the activities of brominated furanones and shed new light on persister control.     

Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health

Phytoestrogens are a class of bioactive compounds derived from plants and exert various estrogenic and antiestrogenic effects. Estrogen deficiency osteoporosis has become a serious problem in elderly women. The use of ovariectomized (OVX) rat or mice models to simulate the postmenopausal condition is well established. This review aimed to clarify the sources, biochemistry, absorption, metabolism, and mode of action of phytoestrogens on bone health in intervention studies. In vitro, phytoestrogens promote protein synthesis, osteoprotegerin/receptor activation of nuclear factor-kappa B ligand ratio, and mineralization by osteoblast-like cells (MC3T3-E1). In the OVX murine model, administration of phytoestrogens can inhibit differentiation and activation of osteoclasts, expression of tartrate-resistant acid phosphatase, and secretion of pyridinoline compound. Phytoestrogens also enhance bone formation and increase bone mineral density and levels of alkaline phosphatase, osteocalcin, osteopontin, and α1(I) collagen. Results of mechanistic studies have indicated that phytoestrogens suppress the rate of bone resorption and enhance the rate of bone formation.     

白顶鹀(Emberiza stewarti)——中国鸟类新纪录

白顶鹀(Emberiza stewarti)为中亚特有物种,比较罕见。2013年5月12日,喀什地区观鸟爱好者与户外摄影人在新疆乌恰县境内膘尔托阔依乡(39°20'N和75°05'E,海拔2 100 m)帕米尔东麓拍摄到一只雄性白顶鹀照片,经过查阅文献,确认是中国鸟类新纪录。     

光周期对四眼斑水龟繁殖影响

为探讨光周期对四眼斑水龟(Sacalia quadriocellata)繁殖的影响,于2008年10月至2009年9月对其进行光周期实验.将39只成体分成短光照组、长光照组和对照组,每个组别中样本量均为7♀、66.每月用超声波技术对雌性个体进行卵泡数量、大小的检测,并用X光投射法确定硬壳卵数;每半月对雄性进行录像观察.结果表明:三个实验组卵泡数量和卵泡大小表现出明显的周期性,原始卵泡从8月份开始生长发育,卵泡数量在11月份最多,尺寸在12月份也达到最大值;光周期对雌性卵泡数量和卵泡大小的发育有影响,短光照组检测到的总卵泡数高于长光照组和对照组,其中短光照组卵泡数与对照组卵泡数差异显著(P＜0.05),长光照组卵泡尺寸相对于另外2个实验组显著变小(P＜0.01);光周期对雌性产卵数和雄性发情强度无影响(P＞0.05).光周期对四眼斑水龟雌雄个体性腺发育的作用不同,缩短光照对雌性繁殖有促进作用,延长光照对雄性发情强度在特定阶段具有一定促进作用.     

铜尾矿复垦地土壤动物群落的恢复

土壤动物在退化生态系统的恢复与重建中发挥着重要作用.为了解铜尾矿复垦地区土壤动物群落特征的变化规律,采用样带法和陷阱法对安徽铜陵市林冲铜尾矿复垦地及其外围林灌地土壤动物群落进行调查.样带法共获得土壤动物3 154只,隶属5门10纲,共计27个类群,优势类群为线虫纲、弹尾目和蜱螨目,常见类群为猛水蚤目和鞘翅目幼虫;陷阱法共获得土壤动物2 160只,主要有弹尾目、膜翅目、双尾目、蜘蛛目、倍足纲和寡毛纲等12类群.自铜尾矿复垦地中心到外围林灌地,土壤动物密度和丰度呈递增趋势;与外围林灌地相比,铜尾矿复垦地土壤动物群落多样性DG指数较低而Shannon-Wiener指数较高;与外围林灌地距离越大,与外围林灌地群落相似性系数越小;表聚性越明显.地表土壤动物从外围林灌地迁入铜尾矿复垦地的多度和丰富度随间隔距离的增加而不断减少,随调查时间的延长而增加,随外围林灌类型的变化而变化.上述结果表明,铜尾矿复垦地及其外围林灌地土壤动物群落之间具有明显的时空差异性和渐变性,这为外围林灌地土壤动物迁入铜尾矿复垦地定居提供了证据.