Characterization of miRNAs responsive to exogenous ethylene in grapevine berries at whole genome level

MicroRNAs (miRNAs) are critical regulators of various biological and metabolic processes of plants. Numerous miRNAs and their functions have been identified and analyzed in many plants. However, till now, the involvement of miRNAs in the response of grapevine berries to ethylene has not been reported yet. Here, Solexa technology was employed to deeply sequence small RNA libraries constructed from grapevine berries treated with and without ethylene. A total of 124 known and 78 novel miRNAs were identified. Among these miRNAs, 162 miRNAs were clearly responsive to ethylene, with 55 downregulated, 59 upregulated, and 14 unchanged miRNAs detected only in the control. The other 35 miRNAs responsive to ethylene were induced by ethylene and detected only in the ethylene-treated grapevine materials. Expression analysis of 27 conserved and 26 novel miRNAs revealed that 13 conserved and 18 novel ones were regulated by ethylene during the whole development of grapevine berries. High-throughput sequencing and qRT-PCR assays revealed consistent results on the expression results of ethylene-responsive miRNAs. Moreover, 90 target genes for 34 novel miRNAs were predicted, most of which were involved in responses to various stresses, especially like exogenous ethylene treatment. The identified miRNAs may be mainly involved in grapevine berry development and response to various environmental conditions.     

安徽东至华龙洞出土的人类化石

2006年在安徽省东至县华龙洞发现了1枚人类下颌第二臼齿和2件可以拼接在一起的额骨碎片化石。根据华龙洞动物群组成及地层情况,初步确定华龙洞化石层的时代为更新世中期。本文对在华龙洞发现的人类头骨和牙齿化石的形态特征进行了观测,并与相关古人类标本进行了对比。研究发现:华龙洞人额骨和下颌臼齿都呈现出一系列常见于东亚直立人的特征。华龙洞额骨曲度较小,具有粗壮的颞线和较厚的骨壁。此外,华龙洞额骨还具有额中缝结构和扩大的额窦。华龙洞下颌第二臼齿总体显得比较粗壮。齿冠咬合面具有第五尖、第六尖和第七尖。齿冠尺寸明显大于早期现代人、现代人类和欧洲更新世中期人类,位于直立人变异范围。结合对华龙洞人类额骨和牙齿形态对比所揭示的形态特点,在华龙洞发现的人类化石可能代表着生活在更新世中期的直立人。     

Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase

N6022 is a novel, first-in-class drug with potent inhibitory activity against S-nitrosoglutathione reductase (GSNOR), an enzyme important in the metabolism of S-nitrosoglutathione (GSNO) and in the maintenance of nitric oxide (NO) homeostasis. Inhibition of GSNOR by N6022 and related compounds has shown safety and efficacy in animal models of asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease [Sun, X., et al. (2011) ACS Med. Chem. Lett. 2, 402-406]. N6022 is currently in early phase clinical studies in humans. We show here that N6022 is a tight-binding, specific, and fully reversible inhibitor of GSNOR with an IC(50) of 8 nM and a K(i) of 2.5 nM. We accounted for the fact that the NAD(+)- and NADH-dependent oxidation and reduction reactions, catalyzed by GSNOR are bisubstrate in nature in our calculations. N6022 binds in the GSNO substrate binding pocket like a competitive inhibitor, although in kinetic assays it behaves with a mixed uncompetitive mode of inhibition (MOI) toward the GSNO substrate and a mixed competitive MOI toward the formaldehyde adduct, S-hydroxymethylglutathione (HMGSH). N6022 is uncompetitive with cofactors NAD(+) and NADH. The potency, specificity, and MOI of related GSNOR inhibitor compounds are also reported.     

应用兔抗大熊猫免疫球蛋白G血清探讨大熊猫的分类地位

从大熊猫血清中纯化出免疫球蛋白(IgG),以此作为抗原免疫家兔,获得兔抗大熊猫IgG血清。以黑熊、小熊猫、狗、猫等动物血清为抗原,兔抗大熊猫IgG 血清为抗体．进行了免疫扩散和微量免疫电泳实验。 实验结果表明,收集的食肉目动物：黑熊、小熊猫、狗、猫的血清都可与兔抗大熊猫GIg血清进行沉淀反应,其中尤以黑熊的反应最强且与大熊猫的反应沉淀线完全融合;小熊猫、狗、猫反应较弱且融入大熊猫反应沉淀线后形成树板状。从此看出大熊猫lgG 与黑熊的IgG最相似,从亲缘关系上讲,二者更为接近,大熊猫反应属熊科。     

PDTD: a web-accessible protein database for drug target identification

Background  

Target identification is important for modern drug discovery. With the advances in the development of molecular docking, potential binding proteins may be discovered by docking a small molecule to a repository of proteins with three-dimensional (3D) structures. To complete this task, a reverse docking program and a drug target database with 3D structures are necessary. To this end, we have developed a web server tool, TarFisDock (TargetFishingDocking), which has been used widely by others. Recently, we have constructed a protein target database,PotentialDrugTargetDatabase (PDTD), and have integrated PDTD with TarFisDock. This combination aims to assist target identification and validation.