HaploShare: identification of extended haplotypes shared by cases and evaluation against controls

Recent founder mutations may play important roles in complex diseases and Mendelian disorders. Detecting shared haplotypes that are identical by descent (IBD) could facilitate discovery of these mutations. Several programs address this, but are usually limited to detecting pair-wise shared haplotypes and not providing a comparison of cases and controls. We present a novel algorithm and software package, HaploShare, which detects extended haplotypes that are shared by multiple individuals, and allows comparisons between cases and controls. Testing on simulated and real cases demonstrated significant improvements in detection power and reduction of false positive rate by HaploShare relative to other programs.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0662-9) contains supplementary material, which is available to authorized users.     

Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N‐type Ca2+ channels and release machinery

α₁‐adrenoceptors (α₁‐ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α₁‐ARs stimulation enhances glutamatergic transmission via both pre‐ and post‐synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre‐synaptic mechanisms may contribute to α₁‐ARs‐induced enhancement of glutamate release. In this study, we blocked the possible post‐synaptic action mediated by α₁‐ARs to investigate how α₁‐ARs activation regulates pre‐synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α₁‐ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe‐induced potentiation was mediated by enhancing pre‐synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C‐dependent pathway. The mechanisms of Phe‐induced potentiation included interaction with both glutamate release machinery and N‐type Ca²⁺ channels, probably via a pre‐synaptic G_q/phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α₁‐ARs‐mediated influence on PFC cognitive functions.

     

Hydrogen sulfide decreases the levels of ROS by inhibiting mitochondrial complex IV and increasing SOD activities in cardiomyocytes under ischemia/reperfusion

Inhibition of oxidative stress has been reported to be involved in the cardioprotective effects of hydrogen sulfide (H(2)S) during ischemia/reperfusion (I/R). However, the mechanism whereby H(2)S regulates the level of cardiac reactive oxygen species (ROS) during I/R remains unclear. Therefore, we investigated the effects of H(2)S on pathways that generate and scavenge ROS. Our results show that pretreating rat neonatal cardiomyocytes with NaHS, a H(2)S donor, reduced the levels of ROS during the hypoxia/reoxygenation (H/R) condition. We found that H(2)S inhibited mitochondrial complex IV activity and increased the activities of superoxide dismutases (SODs), including Mn-SOD and CuZn-SOD. Further studies indicated that H(2)S up-regulated the expression of Mn-SOD but not CuZn-SOD. Using a cell-free system, we showed that H(2)S activates CuZn-SOD. An isothermal titration calorimetry (ITC) analysis indicated that H(2)S directly interacts with CuZn-SOD. Taken together, H(2)S inhibits mitochondrial complex IV and activates SOD to decrease the levels of ROS in cardiomyocytes during I/R.     

Effects of Ceratocystis fimbriata on phenolics content, PPO and PAL activity in sweet potato

选用对甘薯黑斑病抗性不同的品种南京-92(高抗)和烟台-252(高感)的叶片为材料,研究黑斑病对甘薯叶总酚含量、绿原酸含量、类黄酮含量以及苯丙氨酸解氨酶(PAL)活性和酚氧化酶(PPO)活性的影响.结果表明:在未受黑斑病侵染时,南京-92叶片中类黄酮含量、绿原酸含量、PAL活性显著或极显著高于烟台-252,可以作为选育和鉴定抗黑斑病品种的生理指标,但总酚含量和PPO活性差异不显著.接种后2～8 d内,南京-92叶片内总酚含量和PPO活性增加迅速,与烟台-252达到显著或极显著差异,总酚含量和PPO活性的上升速度快、保持时间长,有利于提高对黑斑病的抵抗能力.     

Cry1Ac杀虫蛋白对粘虫中肠几种酶活性的影响

为阐明Bt杀虫蛋白对次要靶标害虫粘虫Mythimna separata (Walker) （鳞翅目： 夜蛾科）的生理学影响, 本研究分析比较了粘虫高龄幼虫在室内取食低剂量Cry1Ac杀虫蛋白6, 12, 24和36 h后, 其体内主要的解毒酶（酯酶和谷胱甘肽-S-转移酶）、 保护酶（超氧化物歧化酶、 过氧化氢酶和过氧化物酶）和中肠蛋白酶（总蛋白酶、 强碱性类胰蛋白酶、 弱碱性类胰蛋白酶和类胰凝乳蛋白酶）等活性的变化。结果表明, 取食Cry1Ac杀虫蛋白后, 粘虫幼虫体内相关酶活力呈现不同的变化趋势： （1）酯酶、 谷胱甘肽-S-转移酶、 过氧化物酶(POD)、 类胰蛋白酶和类胰凝乳蛋白酶活力较对照显著降低（P<0.05）; （2）超氧化物歧化酶(SOD) 活力较对照显著升高（P<0.05）; （3）过氧化氢酶(CAT) 活力于6, 12和24 h显著低于对照（P<0.05）, 36 h时显著高于对照（P<0.05）。结果提示Cry1Ac杀虫蛋白主要通过抑制粘虫幼虫中肠解毒酶和蛋白酶的活性, 扰乱SOD, CAT 和POD 3种保护酶的动态平衡而干扰幼虫的正常生理代谢, 从而起到毒杀粘虫的作用。     

Acetaminophen inhibits cytochrome c redox cycling induced lipid peroxidation

Recent evidence indicates that site-specific crosstalk between O-GlcNAcylation and phosphorylation and the O-GlcNAcylation of kinases play an important role in regulating cell signaling. However, relatively few kinases have been analyzed for O-GlcNAcylation. Here, we identify additional kinases that are substrates for O-GlcNAcylation using an in vitro OGT assay on a functional kinase array. Forty-two kinases were O-GlcNAcylated in vitro, representing 39% of the kinases on the array. In addition, we confirmed the in vivo O-GlcNAcylation of three identified kinases. Our results suggest that O-GlcNAcylation may directly regulate a substantial number of kinases and illustrates the increasingly complex relationship between O-GlcNAcylation and phosphorylation in cellular signaling.     

灭幼脲Ⅲ号在好气水环境中的降解代谢的初步研究

本文研究了新农药灭幼脲Ⅲ号在好气水环境中的降解与代谢。在避光条件下,观察了灭菌组与实验组中灭幼脲Ⅲ号及其主要代谢产物的消长过程,比较了它的化学水解与微生物降解的差异。在室内模拟好气系统中,研究了母体化合物在水体中的残留动态和生物降解半衰期,及其初期主要代谢途径的转化产物,同时分别用高效液相色谱法,紫外吸收光谱扫描,以及特征有机质谱图,对灭幼脲Ⅲ号的两种主要代谢产物进行了定性定量测定。结果表明:灭幼脲Ⅲ号在室内好气环境中较易水解,而且水中微生物的存在能加速它的降解,母体化合物在水体中初期代谢主要途径为分子中的苯甲酰碳与脲氮键首先开裂,生成邻氯苯甲酸(CBA)和对氯苯基脲素(CPU)。     

韦氏鳞(虫八)的精子结构(双尾目)

韦氏鳞(虫八)(Lepidocampa weberi)精子为细长的鞭毛精子,成束排列成精索。顶体由三层结构组成;核圆柱形,接于顶体后;鞭毛轴丝微管式为“9+9+2”,9条副微管排列不整齐,集中于轴丝的一侧;两条细长的线粒体衍生物位于顶体、核与轴丝之间,贯穿于精子中部;精子尾部围有大量片层结构。结果表明韦氏鳞(虫八)精子与康(虫八)精子较为接近,但可能比康(虫八)精子更为特化。