Inhibition of protein phosphorylation and induction of protein cross-linking in erythrocyte membranes by diamide

This report presents studies on the effect of diamide on protein phosphorylation in erythrocyte membranes. Diamide, a thiol-oxidizing reagent, nonspecifically inhibits cyclic Amp-dependent and -independent autophosphorylation of red cell memvranes, but not the activity of the solubilized membrane cycle AMP-independent protein kinases. Analysis of diamide-treated membranes by gel electrophoresis indicates that diamide is capable of inducing cross-linking of membrane proteins. The action of diamide, both in the inhibition of membrane autophosphorylation and in the cross-linking of membrane proteins, is very similar to that of Cu2+. o-phenanthroline complex. Our data indicate that diamide inhibits erythrocyte membrane autophosphorylation by perturbing the protein substrates.     

碳排放影响下的中国省域土地利用效率差异动态变化与影响因素

土地利用效率是衡量区域经济社会系统运行质量的重要参数。在构建了考虑非期望产出的土地利用效率评价指标体系基础之上,综合运用Super SBM-undesirable DEA和多元统计等研究方法,分析了2003—2016年碳排放影响下的中国省域土地利用效率的时空特征及其影响因素。研究结果表明:中国区域土地利用效率处于中低水平,碳排放非期望产出降低了15%的土地利用效率水平;与全国发展水平空间格局一致,土地利用效率省际差异在空间上呈现出自东向西逐渐递减的分异特征;2003—2016年,土地利用效率演化呈现出"U"型演进特征,区域差异呈现收敛态势;不考虑非期望产出的土地利用效率水平呈现下降态势;非期望产出和能源消费投入过大成为土地利用效率提升的主要限制因素。经济发展水平、对外开放程度以及固定资产投资对土地利用效率的提升起到了显著的正向作用;现阶段城镇化水平的增加对土地利用效率的提升具有微弱促进作用,且仅在东部地区具有显著性。基于松弛变量冗余度和影响因素分析,针对不同区域土地利用效率低效的差异性因素,提出了相应的对策措施。     

皮氏菊头蝠(Rhinolophus pearsoni)的栖息生态特征

皮氏菊头蝠(Rhinolophus pearsoni)是我国南方典型的洞栖食虫性蝙蝠,具有重要的生态意义。近年于湘西州及张家界市的25个溶洞中共记录到该蝠450只次,对其栖息生态特征(空间分布、姿势、体温、栖点温度和栖点安全性等)进行了较为系统的观测。结果表明:该蝠的栖点主要集中分布于离洞口440 m之内的洞段(占99.3%),栖点高度通常介于2—10 m之间(84%),主要采取双足倒挂的姿势栖息于洞顶壁或侧壁,但单足倒挂的栖息姿势也较为常见(36.2%)。体温介于10.7—25.2℃,体温总是稍高于栖点温度,但两者之间无显著性差异(P0.05),且两者呈线性正相关。约64%的栖点"安全性高",而"安全性低"和"安全性中"的栖点分别占17.6%和18.4%。减少对洞穴的人为干扰是保护该物种的有效途径。     

Enhanced Orai1-mediated store-operated Ca2+ channel/calpain signaling contributes to high glucose-induced podocyte injury

Podocyte injury induced by hyperglycemia is the main cause of kidney dysfunction in diabetic nephropathy. However, the underlying mechanism is unclear. Store-operated Ca²⁺ entry (SOCE) regulates a diversity of cellular processes in a variety of cell types. Calpain, a Ca²⁺-dependent cysteine protease, was recently shown to be involved in podocyte injury. In the present study, we sought to determine whether increased SOCE contributed to high glucose (HG)–induced podocyte injury through activation of the calpain pathway. In cultured human podocytes, whole-cell patch clamp indicated the presence of functional store-operated Ca²⁺ channels, which are composed of Orai1 proteins and mediate SOCE. Western blots showed that HG treatment increased the protein abundance of Orai1 in a dose-dependent manner. Consistently, calcium imaging experiments revealed that SOCE was significantly enhanced in podocytes following HG treatment. Furthermore, HG treatment caused overt podocyte F-actin disorganization as well as a significant decrease in nephrin protein abundance, both of which are indications of podocyte injury. These podocyte injury responses were significantly blunted by both pharmacological inhibition of Orai1 using the small molecule inhibitor BTP2 or by genetic deletion of Orai1 using CRISPR-Cas9 lentivirus. Moreover, activation of SOCE by thapsigargin, an inhibitor of Ca²⁺ pump on the endoplasmic/sarcoplasmic reticulum membrane, significantly increased the activity of calpain, which was inhibited by BTP2. Finally, the calpain-1/calpain-2 inhibitor calpeptin significantly blunted the nephrin protein reduction induced by HG treatment. Taken together, our results suggest that enhanced signaling via an Orai1/SOCE/Calpain axis contributes to HG-induced podocyte injury.     

STE20 phosphorylation of AMPK-related kinases revealed by biochemical purifications combined with genetics

We have recently purified mammalian sterile 20 (STE20)–like kinase 3 (MST3) as a kinase for the multifunctional kinases, AMP-activated protein kinase–related kinases (ARKs). However, unresolved questions from this study, such as remaining phosphorylation activities following deletion of the Mst3 gene from human embryonic kidney cells and mice, led us to conclude that there were additional kinases for ARKs. Further purification recovered Ca²⁺/calmodulin-dependent protein kinase kinases 1 and 2 (CaMKK1 and 2), and a third round of purification revealed mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5) as potential kinases of ARKs. We then demonstrated that MST3 and MAP4K5, both belonging to the STE20-like kinase family, could phosphorylate all 14 ARKs both in vivo and in vitro. Further examination of all 28 STE20 kinases detected variable phosphorylation activity on AMP-activated protein kinase (AMPK) and the salt-inducible kinase 3 (SIK3). Taken together, our results have revealed novel relationships between STE20 kinases and ARKs, with potential physiological and pathological implications.     

旅游环境舒适度评价及其时空分异——以杭州西湖为例

旅游环境舒适度是影响旅游者出行决策和消费行为的重要因素,进一步影响到目的地适游期长短和旅游设施利用率。影响旅游舒适度的因素主要包括气候与环境两方面。以杭州西湖景区为研究对象,尝试将影响舒适度的空气质量、噪音等环境因素与气候因素共同纳入评价体系,选取温度、相对湿度、二氧化碳、一氧化碳、噪音5项指标和6个代表性检测点,进行为期1a定时定点检测,在排除二氧化碳与一氧化碳影响的基础上,构建了旅游环境舒适度评价模型,研究景区尺度存在的旅游环境舒适度时空分异特征。研究发现:不舒适时段主要集中在1月上旬到2月下旬,舒适和较舒适时段主要集中于2月下旬到7月中旬、8月下旬到11月下旬;山区与湖区各项环境指标要优于近城区、游客集聚区及交通繁忙区,平均舒适度山区(1.30)湖心区(1.66)城区(1.82)近城区(2.02)游人集聚区(2.47)交通繁忙区(2.48)。6个观测点在不同时段表现的舒适度差异也不同,差异最大的时段出现在4月中旬到5月中旬,差异最小时段出现在1月上旬到2月下旬。温湿度与噪音存在反向协同作用,引起环境舒适度变化。温湿度舒适时段往往旅游活动频繁,导致噪音升高降低了旅游环境舒适度。温湿度不舒适期旅游活动减少使得声环境相对舒适。     

澜沧江流域暴雨干旱灾害与海温异常波动规律的相关性

基于中国气象局国家气象信息中心提供的澜沧江区域1961—2011年50年气象资料,采用EMD(Empirical Mode Decomposition)分解、均生函数逐步回归模型、相关分析等方法,探讨了澜沧江流域极端天气灾害的变化特征,及其区域极端灾害变化和全球海温异常ENSO(El Nio/La Nia-Southern Oscillation)之间的联系。结果表明:(1)该区域降水和暴雨频次存在多尺度特征,降水量存在2a、7a、15a的变化周期,且主周期为准2 a。(2)降水量和暴雨频度序列的IMF1和IMF2周期在2—7 a之间,与ENSO在年际变化上的信号相吻合,NINO(El Nio)指数无论春夏秋冬或年际都与暴雨和干旱灾害频次呈现负相关,而SOI(Southern Oscillation Index)指数则呈现正相关,其中,NINO指数与干旱相关性指数在秋冬和年际接近-0.3。(3)澜沧江流域暴雨和干旱灾害与ENSO有重要联系,且随着气温升高干旱灾害频次明显增加。研究结果显示区域极端气温灾害的变化与全球气候变暖有某种关联,是全球气候变化的区域响应表现形式之一。     

Sulfated glycosaminoglycans and low-density lipoprotein receptor mediate the cellular entry of Clostridium novyi alpha-toxin

Dear Editor, Clostridium novyi(C.novyi)is a spore-forming anaerobic bacterium and opportunistic pathogen causing severe infectious diseases in humans and animal...     

不同血清型肉毒毒素受体结合域研究进展

肉毒毒素(botulinum neurotoxin, BoNT)是人类已知毒性最强的蛋白质之一,可以引起肌肉松弛麻痹,严重时可导致死亡。肉毒毒素共分为7种血清型(BoNT/A-BoNT/G),根据氨基酸序列差异可进一步分为40多种亚型。肉毒毒素分子结构由3个基本结构域组成：重链羧基端细胞受体结合域、氨基端的易位域和轻链催化域。在运动神经元表面,受体结合域首先与聚唾液酸神经节苷脂结合,随后与突触囊泡蛋白2或突触囊泡结合蛋白结合形成双受体复合物。每种血清型的受体结合域都必须与其相应受体结合才能发挥作用。肉毒毒素的结构功能及其对宿主的作用一直都是研究热点。近年来,因受体结合域可以促进肉毒毒素与运动神经元膜特异性结合,而成为新的研究方向。本综述将概述不同血清型肉毒毒素与受体结合过程中受体结合域结构变化和结合位点差异。通过分析不同血清型及亚型的序列以及受体结合域结构特征,可以更好地了解细胞受体结合域的序列差异和功能,并为肉毒毒素的治疗策略提供新思路。