磷脂酶A2亚型及其与男性生殖相关性研究

磷脂酶A2(phospholipase A2,PLA2)是参与细胞代谢活动、信号转导等过程的重要酶类之一,广泛分布于哺乳动物机体内。随着对磷脂酶A2研究的深入,目前已有30余种磷脂酶A2亚型被逐一鉴定,磷脂酶A2亚型与男性生殖相关性研究也有了新的发现。该文通过对磷脂酶A2的最新亚型分类及其特征、磷脂酶A2在男性生殖系统中的分布、磷脂酶A2参与精子顶体反应及其信号转导通路以及与男性生殖相关的磷脂酶A2亚型等内容进行分析,研究磷脂酶A2在男性生殖系统中发挥的作用及其机制,为男性不育的诊断和治疗提供理论依据和思路策略。     

The antitumor effect of magnetic nanodisks and DNA aptamer conjugates

Here we describe a method of forming large arrays (up to 10⁹ pieces) of free magnetic Ni-nanodisks 50 nm thick coated on both sides with layers of 5 nm thick Au. The antitumor effect of the magnetic nickel gold-coated nanodisks and DNA aptamer conjugates was evaluated in vivo and in vitro. Under the influence of rotating magnetic field, the studied nanodisks can cause the death of Ehrlich ascites carcinoma cells.     

Inactivation of Semicarbazide-Sensitive Amine Oxidase Stabilizes the Established Atherosclerotic Lesions via Inducing the Phenotypic Switch of Smooth Muscle Cells

Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO) activity is associated with the severity of carotid atherosclerosis in clinic, the current study aims to investigate whether SSAO inactivation by semicarbazide is beneficial for established atherosclerotic lesions in LDLr knockout mice on a high-fat/high- cholesterol Western-type diet or after dietary lipid lowering. Despite no impact on plasma total cholesterol levels, the infiltration of circulating monocytes into peripheral tissues, and the size of atherosclerotic lesions, abrogation of SSAO activity resulted in the stabilization of established lesions as evidenced by the increased collagen contents under both conditions. Moreover, SSAO inactivation decreased Ly6C^high monocytosis and lesion macrophage contents in hypercholesterolemic mice, while no effect was observed in mice after normalization of hypercholesterolemia by dietary lipid lowering. Strikingly, abrogation of SSAO activity significantly increased not only the absolute numbers of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic phenotype in established lesions of mice regardless of plasma cholesterol levels. Overall, our data indicate that SSAO inactivation in vivo stabilizes the established plaques mainly via inducing the switch of SMCs from a contractile to a synthetic phenotype. Targeting SSAO activity thus may represent a potential treatment for patients with atherosclerosis.     

Exploring ligand dissociation pathways from aminopeptidase N using random acceleration molecular dynamics simulation

Aminopeptidase N (APN) is a zinc-dependent ectopeptidase involved in cell proliferation, secretion, invasion, and angiogenesis, and is widely recognized as an important cancer target. However, the mechanisms whereby ligands leave the active site of APN remain unknown. Investigating ligand dissociation processes is quite difficult, both in classical simulation methods and in experimental approaches. In this study, random acceleration molecular dynamics (RAMD) simulation was used to investigate the potential dissociation pathways of ligand from APN. The results revealed three pathways (channels A, B and C) for ligand release. Channel A, which matches the hypothetical channel region, was the most preferred region for bestatin to dissociate from the enzyme, and is probably the major channel for the inner bound ligand. In addition, two alternative channels (channels B and C) were shown to be possible pathways for ligand egression. Meanwhile, we identified key residues controlling the dynamic features of APN channels. Identification of the dissociation routes will provide further mechanistic insights into APN, which will benefit the development of more promising APN inhibitors.

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Graphical Abstract The release pathways of bestatin inside active site of aminopeptidase N were simulated using RAMD simulation

     

Hawksbill turtle terra incognita: conservation genetics of?eastern Pacific rookeries

Prior to 2008 and the discovery of several important hawksbill turtle (Eretmochelys imbricata) nesting colonies in the EP (Eastern Pacific), the species was considered virtually absent from the region. Research since that time has yielded new insights into EP hawksbills, salient among them being the use of mangrove estuaries for nesting. These recent revelations have raised interest in the genetic characterization of hawksbills in the EP, studies of which have remained lacking to date. Between 2008 and 2014, we collected tissue samples from 269 nesting hawksbills at nine rookeries across the EP and used mitochondrial DNA sequences (766 bp) to generate the first genetic characterization of rookeries in the region. Our results inform genetic diversity, population differentiation, and phylogeography of the species. Hawksbills in the EP demonstrate low genetic diversity: We identified a total of only seven haplotypes across the region, including five new and two previously identified nesting haplotypes (pooled frequencies of 58.4% and 41.6%, respectively), the former only evident in Central American rookeries. Despite low genetic diversity, we found strong stock structure between the four principal rookeries, suggesting the existence of multiple populations and warranting their recognition as distinct management units. Furthermore, haplotypes EiIP106 and EiIP108 are unique to hawksbills that nest in mangrove estuaries, a behavior found only in hawksbills along Pacific Central America. The detected genetic differentiation supports the existence of a novel mangrove estuary “reproductive ecotype” that may warrant additional conservation attention. From a phylogeographic perspective, our research indicates hawksbills colonized the EP via the Indo‐Pacific, and do not represent relict populations isolated from the Atlantic by the rising of the Panama Isthmus. Low overall genetic diversity in the EP is likely the combined result of few rookeries, extremely small reproductive populations and evolutionarily recent colonization events. Additional research with larger sample sizes and variable markers will help further genetic understanding of hawksbill turtles in the EP.     

Entry of facultative pathogen <Emphasis Type="Italic">Serratia grimesii</Emphasis> into Hela cells. Electron microscopic analysis

Facultative pathogens Serratia grimesii are able to invade eukaryotic cells where they have been found in vacuoles and free in the cytoplasm (Efremova et al., 2001; Bozhokina et al., 2011). However, efficiency of this invasion is low, and the mechanisms of the invasion related to the initial steps of the process are not known. In the present study, we have increased the invasion efficiency by a 24-h-incubation of HeLa cells with N-acetylcysteine (NAC) preceding the infection. In the NAC-pretreated cells, two modes of S. grimesii to enter HeLa cells were observed. In the most cases, the penetration of S. grimesii into the cell was consistent with the “zipper mechanism”, which first step involves specific interaction of bacterial invasin with a host cell surface receptor. However, in some cases, bacteria were trapped by filopodia probably induced by injected bacterial proteins that trigger the bacterial uptake process, as described in the “trigger mechanism” of invasion. To clarify whether two different mechanisms or a predominant one operate during S. grimesii invasion, further elucidation of bacterial and cellular factors involved in the bacteria-host cell interaction should be performed.