The oncolytic peptide LTX-315 triggers necrotic cell death

The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects.     

Fluorine‐Free Noble Salt Anion for High‐Performance All‐Solid‐State Lithium–Sulfur Batteries

Amongst post‐Li‐ion battery technologies, lithium–sulfur (Li–S) batteries have captured an immense interest as one of the most appealing devices from both the industrial and academia sectors. The replacement of conventional liquid electrolytes with solid polymer electrolytes (SPEs) enables not only a safer use of Li metal (Li°) anodes but also a flexible design in the shape of Li–S batteries. However, the practical implementation of SPEs‐based all‐solid‐state Li–S batteries (ASSLSBs) is largely hindered by the shuttling effect of the polysulfide intermediates and the formation of dendritic Li° during the battery operation. Herein, a fluorine‐free noble salt anion, tricyanomethanide [C(CN)₃^?, TCM^?], is proposed as a Li‐ion conducting salt for ASSLSBs. Compared to the widely used perfluorinated anions {e.g., bis(trifluoromethanesulfonyl)imide anion, [N(SO₂CF₃)₂)]^?, TFSI^?}, the LiTCM‐based electrolytes show decent ionic conductivity, good thermal stability, and sufficient anodic stability suiting the cell chemistry of ASSLSBs. In particular, the fluorine‐free solid electrolyte interphase layer originating from the decomposition of LiTCM exhibits a good mechanical integrity and Li‐ion conductivity, which allows the LiTCM‐based Li–S cells to be cycled with good rate capability and Coulombic efficiency. The LiTCM‐based electrolytes are believed to be the most promising candidates for building cost‐effective and high energy density ASSLSBs in the near future.     

抗寒剂诱导仁用杏花期抗寒力研究

在仁用杏花芽膨大期分别喷施ABA、‘杏花防冻剂’、‘冻害必施’和‘天达-2116’等4种抗寒剂,测定花蕾、花朵和幼果中电解质渗出率、SOD和POD活性以及可溶性糖、可溶性蛋白质和MDA含量,研究4种抗寒剂诱导仁用杏花期抗寒力的差异。结果表明,(1)4种抗寒剂均能不同程度地降低仁用杏半致死温度,诱导抗寒力提高,其中,‘杏花防冻剂’对仁用杏抗寒力的诱导效果最好,ABA次之;(2)‘杏花防冻剂’和ABA均能提高仁用杏花期的可溶性糖和可溶性蛋白质含量,增强SOD和POD活性,降低MDA含量,进一步证明抗寒剂可提高仁用杏花期的抗寒能力。     

Up-regulation of kin17 is essential for proliferation of breast cancer

Background

Kin17 is ubiquitously expressed at low levels in human tissue and participates in DNA replication, DNA repair and cell cycle control. Breast cancer cells are characterized by enabling replicative immortality and accumulated DNA damage. However, whether kin17 contributes to breast carcinogenesis remains unknown.

Methodology/Principal Findings

In this study, we show for the first time that kin17 is an important molecule related to breast cancer. Our results show that kin17 expression was markedly increased in clinical breast tumors and was associated with tumor grade, Ki-67 expression, p53 mutation status and progesterone receptor expression, which were assessed in a clinicopathologic characteristics review. Knockdown of kin17 inhibited DNA replication and repair, blocked cell cycle progression and inhibited anchorage-independent growth, while increasing sensitivity to chemotherapy in breast cancer cells. Moreover, kin17 silencing decreased EGF-stimulated cell growth. Furthermore, overexpression of kin17 promoted DNA replication and cell proliferation in MCF-10A.

Conclusions/Significance

Our findings indicate that up-regulation of kin17 is strongly associated with cellular proliferation, DNA replication, DNA damage response and breast cancer development. The increased level of kin17 was not only a consequence of immortalization but also associated with tumorigenesis. Therefore, kin17 could be a novel therapeutic target for inhibiting cell growth in breast cancer.     

Computational resources and tools for antimicrobial peptides

Antimicrobial peptides (AMPs), as evolutionarily conserved components of innate immune system, protect against pathogens including bacteria, fungi, viruses, and parasites. In general, AMPs are relatively small peptides (<10 kDa) with cationic nature and amphipathic structure and have modes of action different from traditional antibiotics. Up to now, there are more than 19 000 AMPs that have been reported, including those isolated from nature sources or by synthesis. They have been considered to be promising substitutes of conventional antibiotics in the quest to address the increasing occurrence of antibiotic resistance. However, most AMPs have modest direct antimicrobial activity, and their mechanisms of action, as well as their structure–activity relationships, are still poorly understood. Computational strategies are invaluable assets to provide insight into the activity of AMPs and thus exploit their potential as a new generation of antimicrobials. This article reviews the advances of AMP databases and computational tools for the prediction and design of new active AMPs. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.     

Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and SYCP2 align by homology but fail to synapse and have possible impaired specificity of chromatin loop attachment

The targeted deletion of the meiotic chromosome core component MmSYCP3 results in chromosome synaptic failure at male meiotic prophase, extended meiotic chromosomes, male sterility, oocyte aneuploidy and absence of the MmSYCP2 chromosome core component. To test the functions of SYCP2 and SYCP3 proteins in the cores, we determined the effect of their deletion on homology recognition by whole chromosome painting and the effect on chromatin loop attachment to the cores with endogenous and exogenous sequences. Because we observed that the alignment of cores is between homologs, it suggested that alignment is not a function of the chromosome core components but might be mediated by chromatin-chromatin interactions. The alignment function therefore appears to be separate from intimate synapsis function of homologous cores that is observed to be defective in the SYCP3-/- males. To examine the functions of the SYCP2 and 3 core proteins in chromatin loop attachment, we measured the loop sizes of the centromeric major satellite chromatin and the organization of an exogenous transgene in SYCP3+/+ and SYCP3-/- males. We observed that these satellite chromatin loops have a normal appearance in SYCP3-/- males, but the loop regulation of a 2-Mb exogenous lambda phage insert appears to be altered. Normally the insert fails to attach to the core except by flanking endogenous sequences, but in the absence of SYCP2 and SYCP3, there appears to be multiple attachments to the core. This suggests that the selective preference for the attachment of mouse sequences to the chromosome core in the wild-type male is impaired in the SYCP3-/- male. Apparently the SYCP2 and SYCP3 proteins function in the specificity of chromatin attachment to the chromosome core.     

Retinal Arteriolar Morphometry Based on Full Width at Half Maximum Analysis of Spectral-Domain Optical Coherence Tomography Images

Objectives

In this study, we develop a microdensitometry method using full width at half maximum (FWHM) analysis of the retinal vascular structure in a spectral-domain optical coherence tomography (SD-OCT) image and present the application of this method in the morphometry of arteriolar changes during hypertension.

Methods

Two raters using manual and FWHM methods measured retinal vessel outer and lumen diameters in SD-OCT images. Inter-rater reproducibility was measured using coefficients of variation (CV), intraclass correlation coefficient and a Bland-Altman plot. OCT images from forty-three eyes of 43 hypertensive patients and 40 eyes of 40 controls were analyzed using an FWHM approach; wall thickness, wall cross-sectional area (WCSA) and wall to lumen ratio (WLR) were subsequently calculated.

Results

Mean difference in inter-rater agreement ranged from -2.713 to 2.658 μm when using a manual method, and ranged from -0.008 to 0.131 μm when using a FWHM approach. The inter-rater CVs were significantly less for the FWHM approach versus the manual method (P < 0.05). Compared with controls, the wall thickness, WCSA and WLR of retinal arterioles were increased in the hypertensive patients, particular in diabetic hypertensive patients.

Conclusions

The microdensitometry method using a FWHM algorithm markedly improved inter-rater reproducibility of arteriolar morphometric analysis, and SD-OCT may represent a promising noninvasive method for in vivo arteriolar morphometry.     

博尔纳病病毒对BALB/c小鼠感染性检测

目的分析博尔纳病病毒（Borna disease virus,BDV）H1766株对BALB/c小鼠的感染性。方法选择病毒滴度为2.0×107FFU/ml的BDV病毒液分别对新生和成年BALB/c小鼠进行脑内接种,并用相同病毒液对原代培养的新生BALB/c小鼠脑细胞进行接种。经过一定时间的病毒作用后分别提取总RNA,采用巢式RT-PCR方法检测BDV-p40基因,并通过免疫组化方法检测脑内接种脑组织中BDV-P40蛋白。结果脑内接种病毒的小鼠脑组织中可以检测到BDV-p40基因和BDV-P40蛋白,培养的小鼠脑细胞中可以检测到BDV-p40基因。结论BDVH1766株可以感染新生和成年的BALB/c小鼠。     

牛源流行性出血病病毒(EHDV)血清10型毒株在我国的分离鉴定

我国存在多种血清型流行性出血热病毒(Epizootic haemorrhagic disease virus,EHDV)的流行,但尚未有关于EHDV-10型毒株的分离报道。为了解云南省EHDV的流行情况,2012～2015年,本研究在云南省设立江城、师宗、芒市三个监控点,定期采集监控动物血液,接种幼仓鼠肾细胞(Baby hamster kidney cell,BHK-21)进行病毒分离;通过PCR检测、血清中和试验、琼脂糖凝胶电泳和电镜观察等方法对分离病毒进行鉴定;对分离毒株的Seg-2/VP2与Seg-3/VP3基因节段进行克隆、测序与序列分析。2013年在云南省师宗县的哨兵牛上分离出一株EHDV毒株(YNSZ-V277-2013),病毒可引起BHK-21细胞出现圆缩、裂解的细胞病变(Cytopathic effect,CPE);电镜下病毒粒子呈球形,无囊膜,表面有大量纤维突,直径在70～80nm之间;病毒基因组dsRNA的琼脂糖凝胶电泳显示分离毒株与其他血清型EHDV一致,呈现"3-3-3"的电泳带型;序列分析显示YNSZ-V277-2013毒株的Seg-2/VP2与Seg-3/VP3序列与日本EHDV-10型毒株(ON-4/N/98)相似度最高,分别为97.5%/98.5%与98.1%/99.8%,证实分离毒株为EHDV-10型;系统发育分析显示YNSZ-V277-2013毒株的Seg-2与日本EHDV-10型毒株(ON-4/N/98)的亲缘关系最近,Seg-3与分离至日本和澳大利亚的EHDV毒株同属Eastern型。本研究首次报道了EHDV-10型毒株在我国的分离以及分离毒株的Seg-2与Seg-3基因序列特征,为进一步开展中国EHDV-10型的流行病学调查与致病性研究提供了基础。     

我国人与犬、猫共患病防控存在的主要问题与对策建议

随着社会经济的发展、城市化进程的加速及人们生活水平的不断提高,越来越多的宠物走进了人们的家庭,在人类社会生活中发挥了积极作用。但同时,宠物也是人兽共患病的重要传染源和传播媒介。与人类关系最为密切的犬、猫在人兽共患病的防控中具有重要的意义。在已报道的200多种主要的人兽共患病中,与宠物犬、猫有直接或间接关系的有70余种。随着宠物犬猫数量的大幅攀升和宠物业的飞速发展,我国人与犬猫共患病可能会出现逐步高发的趋势,疫病防控工作面临着许多问题。为了完善宠物管理制度,建立有效的防疫监督体系,对人与犬猫共患病实行有效的防控,本文就完善法律法规、形成综合管理机制,加强卫生监督、强化无害化处理、培养专业人才以及广泛开展宣传教育等6个方面提出了相关建议。