Cd胁迫对舞毒蛾幼虫食物利用的影响及其Cd的外泌机制

为探明植食性昆虫对受重金属胁迫的寄主植物的生理生态响应机制,本研究用Cd胁迫下银中杨的叶片饲养舞毒蛾幼虫,分析舞毒蛾幼虫对食物的利用情况以及其对Cd的排毒代谢机制.结果表明: 取食Cd胁迫下银中杨的叶片后,舞毒蛾3～6龄幼虫体内的Cd浓度和Cd含量均显著高于对照,但随着幼虫龄期增长,其体内Cd浓度显著降低,而Cd含量有不同程度的提高;舞毒蛾幼虫粪便和虫蜕中的Cd浓度均显著高于对照;舞毒蛾3～5龄幼虫的食物消耗率显著高于对照,而转化率显著低于对照;3～4龄幼虫的食物利用率均与对照差异不显著,但在5龄时显著低于对照.说明在Cd胁迫下,舞毒蛾幼虫能通过有效的排毒代谢途径将体内富集的部分Cd排出体外,且高龄幼虫的排毒代谢能力强于低龄幼虫;舞毒蛾幼虫体质量的增加会对体内的Cd浓度形成一种稀释效应;舞毒蛾幼虫能通过调整食物消耗率和转化率之间的比例,来维持其正常生长发育所需的食物利用率,但超过一定限度后仍会造成食物利用率降低.     

Discovery of (E)-1-amino-4-phenylbut-3-en-2-ol derivatives as novel neuraminidase inhibitors

Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4-phenylbut-3-en-2-ol (C1) had better inhibitory activities than 2-amino-1-arylethan-1-ol derivatives. To our surprise, sulfonation of C1 with 4-methoxybenzenesulfonyl chloride afforded more active inhibitor II with up to 6.4?μM IC₅₀ value against neuraminidase. Furthermore, docking of inhibitor II into the active site of NA found that the H atoms in both NH₂ and OH groups of inhibitor II were the key factors for potency. Molecular docking research did not explained very well the observed structure-activity relationship (SAR) from amino acid residue level, but also aided the discovery of (E)-1-amino-4-phenylbut-3-en-2-ol derivatives as novel and potent NA inhibitors.     

核糖体失活蛋白对核糖体拓扑结构的影响

辛纳毒蛋白和克木毒蛋白是本实验室纯化的2种新RIP,它们的作用位点是大鼠肝核糖体285rRNA的A4324.足迹分析表明除 A4324位外,其上、下文的鸟苷酸、腺苷酸也是辛纳毒蛋白和克木毒蛋白的识别位点.辛纳毒蛋白或克木毒蛋白修饰大鼠肝核糖体后,其rRNA的拓扑结构发生了变化,rRNA茎环结构中的双链区相对增多,核糖体的整体拓扑结构也随之变化,80 S核糖体减少,60 S和 40 S亚基增多.以上结果表明“S/R结构域”修饰后所引发的rRNA及核糖体拓扑结构的变化是RIP抑制蛋白质合成的重要机理之一.     

Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches

Drebrin is a cytoskeleton‐associated protein which can interact with both actin filaments and the tips of microtubules. Its roles have been studied mostly in dendrites, and the functions of drebrin in axons are less well understood. In this study, we analyzed the role of drebrin, through shRNA‐mediated depletion and overexpression, in the collateral branching of chicken embryonic sensory axons. We report that drebrin promotes the formation of axonal filopodia and collateral branches in vivo and in vitro. Live imaging of cytoskeletal dynamics revealed that drebrin promotes the formation of filopodia from precursor structures termed axonal actin patches. Endogenous drebrin localizes to actin patches and depletion studies indicate that drebrin contributes to the development of patches. In filopodia, endogenous drebrin localizes to the proximal portion of the filopodium. Drebrin was found to promote the stability of axonal filopodia and the entry of microtubule plus tips into axonal filopodia. The effects of drebrin on the stabilization of filopodia are independent of its effects on promoting microtubule targeting to filopodia. Inhibition of myosin II induces a redistribution of endogenous drebrin distally into filopodia, and further increases branching in drebrin overexpressing neurons. Finally, a 30 min treatment with the branch‐inducing signal nerve growth factor increases the levels of axonal drebrin. This study determines the specific roles of drebrin in the regulation of the axonal cytoskeleton, and provides evidence that drebrin contributes to the coordination of the actin and microtubule cytoskeleton during the initial stages of axon branching. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1092–1110, 2016     

First report of metazoan parasites from the cichlid Pseudocrenilabrus philander and the cyprinid Enteromius paludinosus in a South African Ramsar wetland

Parasites of two small fish species from a Ramsar wetland in South Africa were studied in 2014–2015. The cichlid Pseudocrenilabrus philander (Weber, 1897) was parasitised by the copepod Lernaea cyprinacea Linnaeus, 1758, the monogenean Gyrodactylus thlapi Christison, Shinn & van As, 2005 and four gryporhynchid metacestode (Cyclophyllidea) species: Paradilepis scolecina (Rudolph, 1819), Paradilepis maleki Khalil, 1961, Neogryporhynchus lasiopeius Baer & Bona, 1960 and Valipora campylancristrota (Wedl, 1855). The cyprinid Enteromius paludinosus (syn. Barbus paludinosus) (Peters, 1852) was infected with the monogenean parasites Dogielius intorquens Crafford, Luus-Powell & Avenant-Oldewage, 2012, Dactylogyrus teresae Mashego, 1983, and three Dactylogyrus spp. These results represent several new locality as well as host records and further contribute information on the parasitic diversity in the Barberspan Ramsar wetland.     

MAPKs and NF-κB-mediated acrylamide-induced neuropathy in rat striatum and human neuroblastoma cells SY5Y

Acrylamide (ACR) is a potent neurotoxin that can be produced during high-temperature food processing, but the underlying toxicological mechanism remains unclear. In this study, the detrimental effects of ACR on the striatal dopaminergic neurons and the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) in ACR-induced neuronal apoptosis were investigated. Acute ACR exposure caused dopaminergic neurons loss and apoptosis as revealed by decreased tyrosine hydroxylase (TH)-positive cells and TH protein level and increased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in the striatum. ACR-decreased glutathione content, increased levels of malondialdehyde, proinflammatory cytokines tumor necrosis factor α, and interleukin 6. In addition, nuclear NF-κB and MAPKs signaling pathway with c-Jun N-terminal kinase (JNK) and p38 were activated by ACR. Specific inhibitors were used to explore the roles of MAPKs and NF-κB pathways in ACR-induced apoptosis in SH-SY5Y cells. Pretreatment with JNK-specific inhibitors SP600125 markedly upregulated the reduced B-cell lymphoma 2 (Bcl-2) content and downregulated the increased Bcl-2-associated X protein (Bax) level and thereby eventually reduced the proportions of early and late apoptotic cells induced by ACR, while p38 suppression by SB202190 only reversed the decrease in Bcl-2 expression. Inhibition of NF-κB by BAY 11-7082 markedly upregulated Bax level and decreased Bcl-2 expression, and eventually increasing the proportions of neuronal apoptosis compared with that in ACR alone. These results suggested that JNK contributed to ACR-induced apoptosis, while NF-κB acted as a protective regulator in response to ACR-induced neuropathy. This study helps to offer a deeper insight into the mechanism of ACR-induced neuropathy.     

三氯杀螨醇对大型溞的毒性和环境雌激素效应

三氯杀螨醇是DDT被禁用以后出现的替代品,在很多国家包括中国在内被广泛用作果树、棉花等的杀螨剂,对高等动物的急性口服毒性很低,但它的慢性毒性较大。已有报道显示由DDT合成而来的三氯杀螨醇可使美国红隼的蛋壳变薄,与某些野生动物如佛罗里达湖中鳄鱼雌性化具相关性,甚至导致人体某些恶性肿瘤等。由于三氯杀螨醇性质非常稳定,残留期长,所以过去对该农药研究热点主要是在蔬菜、果品等食品中的残留及降解动态,而对水生生物的毒性尚未见报道,而且对其雌激素活性的报道仅限于小鼠子宫增重法等活体实验方法,周期长且由于生物个体差异等造成灵敏度低。       

Knockdown of sphingosine kinase 1 inhibits the migration and invasion of human rheumatoid arthritis fibroblast-like synoviocytes by down-regulating the PI3K/AKT activation and MMP-2/9 production in vitro

To investigate the potential regulation of sphingosine kinase 1 (SPHK1) on the migration, invasion, and matrix metalloproteinase (MMP) expression in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). RA-FLS were transfected control siRNA or SPHK1 siRNA. The migration and invasion of unmanipulated control, control siRNA or SPHK1 siRNA- transfected RA-FLS in vitro were measured by the transwell system. The relative levels of SPHK1, PI3K, and AKT as well as AKT phosphorylation in RA-FLS were determined by Western blot. The levels of MMP-2/9 secreted by RA-FLS were detected by ELISA. Knockdown of SPHK1 significantly inhibited the spontaneous migration and invasion of RA-FLS, accompanied by significantly reduced levels of PI3K expression and AKT phosphorylation. Similarly, treatment with LY294002, an inhibitor of the PI3K/AKT pathway, inhibited the migration and invasion of RA-FLS. Knockdown of SPHK1 and treatment with the inhibitor synergistically inhibited the migration and invasion of RA-FLS, by further reducing the levels of PI3K expression and AKT phosphorylation. In addition, knockdown of SPHK1 or treatment with LY294002 inhibited the secretion of MMP-2 and MMP-9, and both synergistically reduced the production of MMP-2 and MMP-9 in RA-FLS in vitro. Knockdown of SPHK1 expression inhibits the PI3K/AKT activation, MMP-2 and MMP-9 expression, and human RA-FLS migration and invasion in vitro. Potentially, SPHK1 may be a novel therapeutic target for RA.