温度变化对油菜及其伴生杂草种苗生长和幼苗生理特性的影响

以目前大面积栽培的甘蓝型油菜(Brassica napus) ‘秦优10号’和其田间常见的8种杂草播娘蒿(Descurainia sophia)、泽漆(Euphorbia helioscopia)、野燕麦(Avena fatua)、棒头草(Polypogon fugax)、婆婆纳(Veronica didyma)、看麦娘(Alopecurus aequalis)、灰绿藜(Chenopodium glaucum)、反枝苋(Amaranthus retroflexus)为试验材料, 利用人工气候培养箱控温, 研究了10 ℃/5 ℃ (昼/夜)、18 ℃/10 ℃、25 ℃/20 ℃、35 ℃/30 ℃、40 ℃/35 ℃不同温度幅度处理对它们的发芽势、发芽率、幼苗形态及生理指标的影响, 旨在为预测气候变化环境下油菜田恶性靶标杂草的演替趋势提供参考依据。试验结果表明: 不同供试杂草对温度变化表现出明显的适应性差异, 看麦娘、灰绿藜和反枝苋的最适萌发温度偏高, 如反枝苋在高温处理(40 ℃/35 ℃)下种子的发芽率达到最高(91%); 而播娘蒿、泽漆、野燕麦、棒头草、婆婆纳种子的最适萌发温度主要集中于10-18 ℃范围内。进一步测试研究表明, 高温处理(40 ℃/35 ℃)下, 反枝苋幼苗生长旺盛, 体内丙二醛的积累也明显低于低温(10 ℃/5 ℃)处理, 可溶性糖和可溶性蛋白含量以及保护酶活性也较高, 表明反枝苋对高温胁迫有较好的适应性, 灰绿藜对高温的响应与反枝苋相似, 在高温气候年份, 要严防这2种草害加重; 而在低温处理(10 ℃/5 ℃)下, 野燕麦的种子萌发率达到100%, 其幼苗生长旺盛, 体内可溶性糖和可溶性蛋白含量及保护酶活性较高, 播娘蒿对低温胁迫的响应类似于野燕麦, 因此在寒冷年份需加强对野燕麦和播娘蒿草害的预防。供试油菜品种相对于所有供试杂草对温度变化的适应性更好, 其种子在不同温度处理下均保持较稳定的高发芽率, 且幼苗长势良好, 表明‘秦优10号’是一个对温度变化适应性很好的油菜品种。     

基于网络特征的药物靶蛋白识别

蛋白质很少孤立得发挥作用,往往通过网络中彼此互作来共同行使功能.因此分析药物靶蛋白在生物学网络中的性质将十分有助于从信息学角度理解药物的作用机制.但目前尚无研究对药物靶蛋白在人类蛋白质互作网络中的拓扑特性给与具体的分析和描述.本文首先将药物靶蛋白映射到人类蛋白质互作网络中,进而分析了药物作用靶蛋白在互作网络中的5种拓扑指标,并与互作网络中全蛋白质组集合及非药物靶点集合的拓扑指标进行了对比.结果显示,药物靶蛋白之间具有更高的连通性,信息能够得到更快得传递.基于这些拓扑特征,将互作网络中的所有蛋白进行排序.发现排序在前100位的蛋白中有48个是Drugbank中记录的药物靶点,另外的52个蛋白中有9个蛋白已在TTD,Matador等数据库中被记录为药物靶点,还有部分蛋白通过文献检索被证实为药物靶点.     

The Ca2+-dependent DNases are Involved in Secondary Xylem Development in Eucommia ulmoides

Secondary xylem development has long been recognized as a typical case of programmed cell death (PCD) in plants. During PCD, the degradation of genomic DNA is catalyzed by endonucleases. However, to date, no endonuclease has been shown to participate in secondary xylem development. Two novel Ca 2+ -dependent DNase genes, EuCaN1 and EuCaN2, were identified from the differentiating secondary xylem of the tree Eucommia ulmoides Oliv., their functions were studied by DNase activity assay, in situ hybridization, protein immunolocalization and virus-induced gene silencing experiments. Full-length cDNAs of EuCaN1 and EuCaN2 contained an open reading frame of 987 bp, encoding two proteins of 328 amino acids with SNase-like functional domains. The genomic DNA sequence for EuCaN1 had no introns, while EuCaN2 had 8 introns. EuCaN1 and EuCaN2 digested ssDNA and dsDNA with Ca 2+ -dependence at neutral pH. Their expression was confined to differentiating secondary xylem cells and the proteins were localized in the nucleus. Their activity dynamics was closely correlated with secondary xylem development. Secondary xylem cell differentiation is influenced by RNAi of endonuclease genes. The results provide evidence that the Ca 2+ -dependent DNases are involved in secondary xylem development.     

Glycogen synthase kinase 3β inhibition synergizes with PARP inhibitors through the induction of homologous recombination deficiency in colorectal cancer

Monotherapy with poly ADP-ribose polymerase (PARP) inhibitors results in a limited objective response rate (≤60% in most cases) in patients with homologous recombination repair (HRR)-deficient cancer, which suggests a high rate of resistance in this subset of patients to PARP inhibitors (PARPi). To overcome resistance to PARPi and to broaden their clinical use, we performed high-throughput screening of 99 anticancer drugs in combination with PARPi to identify potential therapeutic combinations. Here, we found that GSK3 inhibitors (GSK3i) exhibited a strong synergistic effect with PARPi in a panel of colorectal cancer (CRC) cell lines with diverse genetic backgrounds. The combination of GSK3β and PARP inhibition causes replication stress and DNA double-strand breaks, resulting in increased anaphase bridges and abnormal spindles. Mechanistically, inhibition or genetic depletion of GSK3β was found to impair the HRR of DNA and reduce the mRNA and protein level of BRCA1. Finally, we demonstrated that inhibition or depletion of GSK3β could enhance the in vivo sensitivity to simmiparib without toxicity. Our results provide a mechanistic understanding of the combination of PARP and GSK3 inhibition, and support the clinical development of this combination therapy for CRC patients.Subject terms: Cancer therapeutic resistance, Targeted therapies