Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity

Although 5-fluorouracil (5-FU) plus leucovorin (LV) is a standard chemotherapy regimen for colorectal cancer, the factors that determine the LV-mediated enhancement of the antitumor activity of 5-FU have remained unknown. We investigated the roles of folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH), which are the main enzymes involved in folate metabolism, in the effect of LV. LV enhanced the anticancer activity of 5-FU and the level of reduced folate in human colon cancer cells. Small-interfering RNA (siRNA) transfected into DLD-1 cells to downregulate FPGS reduced the basal level of reduced folate, the folate level after LV treatment, and the enhancement of 5-fluoro-2′-deoxyuridine (FdUrd)-induced cytotoxicity elicited by LV. By contrast, the downregulation of GGH by siRNA increased cellular sensitivity to FdUrd combined with LV. These results suggest that FPGS and GGH expression levels in tumors are determinants of the efficacy of LV in enhancing the antitumor activity of 5-FU.     

内蒙古呼伦贝尔沙地不同樟子松林竞争强度的比较

利用全林木定位和单木竞争指数模型, 以受到林火干扰的樟子松林为例,分析了呼伦贝尔沙地樟子松林的竞争强度.结果表明：同一样地中,死亡林木的竞争强度均比较接近;活立木、全部林木中,伴生树种的竞争强度是樟子松的2～3倍;樟子松的竞争压力主要来自于种内,伴生树种的竞争则主要来自于种间.林火干扰与无林火（对照）样地间的比较表明,林火干扰样地樟子松活立木的竞争强度均显著小于对照样地;活立木竞争强度与其胸径间均服从幂函数关系(CI=AD^-B).地表火干扰可显著降低林木个体间的竞争强度,有利于存活林木个体的生长发育和大径阶林木的培育.     

包含BTB锌指结构的新基因Bsg2结构特性及其在发育阶段的组织表达特异性

通过消减差异筛选法寻找小鼠胚胎发育过程中在脑中特异表达的基因 .克隆得到的脑特异表达新基因 2 (brainspecificgene 2 ,简称Bsg2 )长 36 91bp ,通过生物信息学方法预测其编码一个含713个氨基酸的锌指蛋白 .此蛋白N端有一个BTB(BR C ,ttkandbab)结构域 ,C端有 9个连续的C2H2锌指结构 .该基因定位在小鼠 12号染色体上 ,包含 1个内含子和 2个外显子 .应用生物信息学和RT PCR方法分别检验该基因在小鼠各组织中的表达 .结果表明 ,Bsg2基因在小鼠胚胎及成体的各组织中普遍表达 ,在脾、肾、睾丸、肠、子宫和脑的表达水平较强 .利用整体 (wholemount)原位杂交研究其时空表达模式 .结果显示 ,Bsg2在早期的小鼠胚胎和不同时期鸡胚的头部均特异表达 ,在11d鼠胚的肢芽里也有较强的表达 .Bsg2基因的结构和表达特征预示它编码 1个具有DNA结合功能的转录调控因子 ,同时揭示它在脑的发育和器官形成过程中发挥着重要作用     

Demographic history of the Tibetan antelope Pantholops hodgsoni (chiru)

Abstract The Tibetan antelope (chiru, Pantholops hodgsoni), a heavily poached species and symbol of the Qinghai‐Tibetan Plateau (QTP), is noted worldwide for its special calving migration. This species originated in the early Quaternary and it is interesting to know how the following climatic oscillations affected its demographic dynamics in the climate‐sensitive QTP. In this study, we analyzed the mitochondrial D‐loop region from 312 individuals sampled in all of the six major populations. We found high rates of gene flow and little genetic differentiation between populations, suggesting that the calving migration may have homogenized the genetic pool of this species. Both mismatch distribution analyses and coalescent simulations suggested that this species experienced a demographic expansion approximately 600–200 Kyr following the retreat of the large glaciers developed in the QTP at 800–600 Kyr, rather than at the end of the last glacial age, as previously suggested, based on a limited sample size. In addition, we found evidence of a chiru population decrease probably related to the human settings at the QTP during the middle Holocene.     

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Endothelin (ET) contributes to the increased systemic vascular resistance and elevated cardiac filling pressures seen in congestive heart failure (CHF). We investigated to what extent ET-mediated vasoconstriction in CHF occurs through an endocrine action of elevated plasma ET or by an autocrine/paracrine mechanism related to induction of vascular ET gene expression. Three weeks of pacing (225 beats/min) induced a marked release of ET-1 from the pulmonary circulation with a sixfold elevation of arterial plasma ET in CHF pigs compared with sham-operated pigs. Arterial plasma ET was the strongest and only independent predictor of systemic vascular resistance. In contrast, vascular preproET-1 and ET-receptor mRNA expression were unaltered or decreased in CHF pigs and did not correlate with indexes of vascular tone. However, myocardial preproET-1 mRNA expression increased twofold in CHF pigs. PreproET-2 and preproET-3 mRNAs were not detectable in cardiovascular tissues. In conclusion, plasma ET was markedly increased because of an augmented release from the pulmonary circulation during CHF, and arterial plasma ET correlated with systemic vascular resistance. The absence of ET induction in the peripheral vasculature suggests that ET increases vascular tone during CHF by an endocrine, not an autocrine/paracrine, mechanism.     

Accumulation of liposome with Sialyl Lewis X to inflammation and tumor region: application to in vivo bio-imaging

We prepared the liposome binding Sialyl Lewis X (SLX) on the surface in order to specifically and efficiently deliver substances (fluorescent materials, chemical substances, proteins, genes, etc.) to inflammation or tumor regions. The liposome with SLX (SLX-Lipo-Cy5.5), in which fluorescent substance Cy5.5 was included, was administered intravenously to arthritis or Ehrlich Ascites Tumor (EAT) bearing mouse, and the accumulation of liposome was observed using two types of in vivo fluorescent imaging equipment. The result was that the accumulation of SLX-Lipo-Cy5.5 to inflammation or tumor regions was significantly higher than the control liposome without sugar chain (Lipo-Cy5.5) at 24 and 48 h after administration. In addition, it was confirmed that this accumulation showed a shift of liposome from blood vessels to the surrounding tissues. Thus, it was proven that this liposome is useful not only as an in vivo bio-imaging reagent but also as a drug delivery system (DDS).     

人体通气状态对动脉血气波浪式幅度的影响*

目的: 本研究旨在发现不同通气模式下动脉血气的变化特点。方法: 选择心功能正常,需要连续监测动脉血流动力学变化的患者6 例,4男2女,年龄（59.00±16.64）岁,体质量（71.67±10.37）kg,左心射血分数（LVEF）（61.33±2.16）%。患者签署知情同意书后,分别于正常呼吸、憋气20 s以及高潮气量过度通气状态下连续15~16次心跳桡动脉、颈静脉逐搏取血,测定PO₂,用于分析三种呼吸状态下动、静脉血气的变化特点。分别比较患者相邻最高和最低值,以验证三种呼吸状态下动、静脉血气是否都存在周期性波浪式信号变化;此外,将患者动、静脉血气周期性波浪式信号的变化幅度进行统计学t检验分析,比较有无差异。结果: 共6例ICU 住院监护患者, 抽取动、静脉血液充满肝素化细长塑化管需要15~16次心跳,即取血需要15~16次心跳,全部覆盖超过2个呼吸周期。患者正常呼吸、憋气20 s以及高潮气量通气状态下动脉血气中PaO₂呈现波浪式变化,幅度分别是（9.96±5.18）mmHg,（5.33±1.55）mmHg和（13.13±7.55）mmHg,分别是各自均值的（8.09±2.43）%,（5.29±2.19）%,（10.40±2.68）%,高通气量呼吸模式波浪式变化幅度大于正常呼吸模式（P<0.05）,正常呼吸模式波浪式变化幅度大于憋气状态（P<0.05）。正常呼吸、憋气20 s以及高潮气量通气状态下静脉血气中PO₂未呈现波浪式变化,幅度分别是（1.63±0.41）mmHg,（1.13±0.41）mmHg和（1.31±0.67）mmHg,分别是各自均值的（3.91±1.22）%,（2.92±1.12）%,（3.33±1.81）%,都显著低于同状态下动脉血气,但组间差异不明显。结论: 分别于三种通气状态下采用连续逐搏动脉取血血气分析法证实,患者高通气状态呼吸时动脉血气的周期性波浪式变化信号增强,憋气时波浪式呼吸变化信号变弱,而静脉血氧分压波浪式变化幅度于三种呼吸状态下都不明显。说明肺通气导致肺换气是影响动脉血液波浪式信号幅度的直接决定性因素。     

西藏墨脱县发现长尾阔嘴鸟

正2015年10月21日,在西藏自治区墨脱县德兴乡(29°20′9.97″N,95°19′13.20″E,海拔780 m)观察到阔嘴鸟2只,该鸟体长约25 cm,顶冠及颈背黑色,头顶具蓝色小点斑,喙呈黄绿色,脸及喉部呈黄色,眼后有一黄色点斑,体呈绿色且两翼有蓝斑,尾呈楔形(图1),经鉴定为长尾阔嘴鸟(Psarisomus dalhousiae)。MacK innon等(2000)认为该鸟种分布于西藏东南部,而Bruce(2003)在《世界鸟类手册》中引用了前者的描述。然而,因缺乏实际观察记录,之后我国鸟类学者的著作中均未将长尾阔嘴鸟列为在西藏有分布的鸟类(郑光美2011)。虽     

不同抗旱性花生品种的根系形态发育及其对干旱胁迫的响应

为明确不同抗旱性花生品种的根系形态发育特征,探讨其根系形态发育特征对不同土壤水分状况的响应机制,在防雨棚旱池内进行土柱栽培试验,研究抗旱型品种“花育22号”、“唐科8号”和干旱敏感型品种“花育23号”3个不同抗旱性花生品种根系形态发育特征及其对干旱胁迫的响应.结果表明:抗旱型品种根系较发达,具有较大的根系生物量、总根长、总根系表面积.干旱胁迫使抗旱型品种根系总表面积和体积增加,而干旱敏感型品种则相反.干旱胁迫显著增加抗旱型品种“花育22号”20 cm以下土层内根长密度分布比例及根系表面积和体积,但“唐科8号”相应根系性状仅在20-40 cm土层内增加;干旱胁迫使干旱敏感型品种“花育23号”40 cm以下土层内各根系性状升高,但未达显著水平且其深层土壤内各根系性状增加幅度小于“花育22号”.花生根系总长、总表面积及0-20 cm土层内根系性状与产量间呈显著或极显著正相关.土壤水分亏缺条件下,花生主要通过增加深层土壤内根长、根系表面积和体积等形态特性,优化空间分布构型,以调节植株对水分的利用.     

半干旱沙地封育草场的植被变化及其与土壤因子间的关系

封育措施是一种主要的草场恢复和重建的措施。通过对半干旱沙地完全封育、季节封育和未封育地的比较分析,量化了不同封育措施下植被变化及其与土壤因子的关系。对3种封育措施群落组成和生物多样性的多响应置换过程(M RPP)分析结果表明,封育改变了群落的组成成分并增加了生物多样性,群落的指示种分析及样方相似性指数计算结果则显示,完全封育(>10a)的群落逐渐向旱生化发展,各植物种分布的空间异质性显著提高,放牧价值开始降低,而季节性封育则明显处于一种非平衡的稳定状态。对不同措施下植物种与土壤因子间关系除趋势对应分析(DCA)和除趋势典范对应分析(DCCA)排序结果表明,土壤水分状况是限制3种措施中植物种组成的决定性因子,生物结皮盖度、土壤有机质和土壤容重等因子均在一定的程度上对水分产生影响,其中最为突出的因子是生物结皮盖度,由于长期缺少牲畜的践踏,完全封育区内结皮发育较好,这也是导致群落向旱生化发展的原因之一,同时一些重要因子诸如降水的时空变化或由此而引发的土壤水分的时空变化在本研究中可能被忽略。相关分析表明3种措施的生物多样性除了受土壤水分状况(土壤含水量和结皮盖度)的影响外,还与土壤速效氮呈正相关,与速效磷呈负相关。