Synthesis and biological evaluation of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.     

GDSL lipase-like 1 regulates systemic resistance associated with ethylene signaling in Arabidopsis

Systemic resistance is induced by necrotizing pathogenic microbes and non-pathogenic rhizobacteria and confers protection against a broad range of pathogens. Here we show that Arabidopsis GDSL LIPASE-LIKE 1 (GLIP1) plays an important role in plant immunity, eliciting both local and systemic resistance in plants. GLIP1 functions independently of salicylic acid but requires ethylene signaling. Enhancement of GLIP1 expression in plants increases resistance to pathogens including Alternaria brassicicola , Erwinia carotovora and Pseudomonas syringae , and limits their growth at the infection site. Furthermore, local treatment with GLIP1 proteins is sufficient for the activation of systemic resistance, inducing both resistance gene expression and pathogen resistance in systemic leaves. The PDF1.2 -inducing activity accumulates in petiole exudates in a GLIP1-dependent manner and is fractionated in the size range of less than 10 kDa as determined by size exclusion chromatography. Our results demonstrate that GLIP1-elicited systemic resistance is dependent on ethylene signaling and provide evidence that GLIP1 may mediate the production of a systemic signaling molecule(s).     

Slow and persistent increase of [Ca2+]c in response to ligation of surface IgM in WEHI-231 cells

WEHI-231 and Bal 17 B cell lines are representative models for immature and mature B cells, respectively. Their regulation of cytosolic Ca(2+) concentration ([Ca(2+)](c)) was compared using fura-2 fluorescence ratiometry. The ligation of B cell antigen receptor (BCR) by anti-IgM antibody induced a slow but large increase of [Ca(2+)](c) in WEHI-231 cells while not in Bal 17 cells. The thapsigargin-induced store-operated Ca(2+) entry (SOCE) of Bal 17 cells reached a steady state which was blocked by 2-aminoethoxydiphenyl borate (2-APB). On the contrary, the thapsigargin-induced SOCE of WEHI-231 cells increased continuously, which was accelerated by 2-APB. The increase of [Ca(2+)](c) by BCR ligation was also enhanced by 2-APB in WEHI-231 cells while blocked in Bal 17 cells. The Mn(2+) quenching study showed that the thapsigargin-, or the BCR ligation-induced Ca(2+) influx pathway of WEHI-231 was hardly permeable to Mn(2+). The intractable increase of [Ca(2+)](c) may explain the mechanism of BCR-driven apoptosis of WEHI-231 cells, a well-known model of clonal deletion of autoreactive immature B cells.     

汉坦病毒感染细胞整合素受体信号转导相关差异表达基因筛选

通过基因芯片技术观察汉坦病毒感染细胞后整合素受体信号转导相关基因的差异表达,以探讨汉坦病毒进入细胞的分子机制。用汉滩病毒76—118株感染原代人胚肺成纤维细胞,同时设立正常对照细胞,于感染后第6h、24h和96h同时抽提感染组与正常对照组细胞总RNA,利用荧光标记dUTP逆转录制备cDNA探针,与人类受体及信号转导类表达谱芯片杂交,并对Cy3、Cy5荧光信号做扫描分析。结果显示有37项基因出现差异表达,其中31项基因在感染后6h出现差异表达,13项下调、18项上调;但在感染后24h和96h分别只有5项和4项基因出现表达差异;而且整合素信号转导通路中的重要基因如一些蛋白激酶相关基因在感染6h表达增强,丝化增强子1在感染6h和96h表达下调,微管相关蛋白1A在感染6h表达上调、感染24h和96h表达下调。这些进一步说明汉坦病毒感染细胞与整合素有关。     

间斑寇蛛的生态学观察与实验

报道间斑寇蛛首次在南方大批量人工养殖成功所获得的行为生态学资料:养殖方法、捕食与食谱、活动规律、蜕皮与体色的关系;温度和湿度对间斑寇蛛活动能力、成活率、蜕皮率的影响;温度和食物对其若蛛生长发育的交互影响作用。间斑寇蛛生长发育的适宜温区是20～30℃,RH55%～75%;最适合温度为25℃,RH65%,苍蝇为较理想的食物。结合野外进行了种群密度的调查、初步分析了其种群分布与栖境生物群落的关系。     

Near Neutral pH Redox Flow Battery with Low Permeability and Long‐Lifetime Phosphonated Viologen Active Species

A highly stable phosphonate‐functionalized viologen is introduced as the redox‐active material in a negative potential electrolyte for aqueous redox flow batteries (ARFBs) operating at nearly neutral pH. The solubility is 1.23 m and the reduction potential is the lowest of any substituted viologen utilized in a flow battery, reaching ?0.462 V versus SHE at pH = 9. The negative charges in both the oxidized and the reduced states of 1,1′‐bis(3‐phosphonopropyl)‐[4,4′‐bipyridine]‐1,1′‐diium dibromide ( BPP?Vi ) effect low permeability in cation exchange membranes and suppress a bimolecular mechanism of viologen decomposition. A flow battery pairing BPP?Vi with a ferrocyanide‐based positive potential electrolyte across an inexpensive, non‐fluorinated cation exchange membrane at pH = 9 exhibits an open‐circuit voltage of 0.9 V and a capacity fade rate of 0.016% per day or 0.00069% per cycle. Overcharging leads to viologen decomposition, causing irreversible capacity fade. This work introduces extremely stable, extremely low‐permeating and low reduction potential redox active materials into near neutral ARFBs.