切尔诺贝利核事故对区域景观格局及生境质量的影响

灾难地景观格局及生境质量演化特征研究对于评估灾难破坏力及其滞后性,揭示人类活动对自然环境的影响机制具有重要意义。基于Landsat系列遥感影像提取切尔诺贝利隔离区景观类型结构,借助景观指数和InVEST模型刻画研究区近49年来的景观格局和生境质量演化轨迹,使用CA-Markov模型模拟核事故对区域生态景观的影响。研究表明：（1）切尔诺贝利核事故改变了隔离区原有的景观结构,导致耕地、建设用地等人为景观数量大幅缩减,土地利用程度显著下降,但核事故未对隔离区当前的景观结构造成实质性负面影响;（2）切尔诺贝利核事故致使隔离区人为干扰减少,植被连通性和集聚度提升,景观格局总体向好发展;（3）隔离区的设立扭转了区内生境质量恶化趋势,由耕地形成的低生境质量区域迅速转变为草地、林地等高生境质量区域,区内生境质量极大改善;（4）切尔诺贝利核事故使得区内高生境质量区域占比提升34%,改变了原有以耕地、建设用地不断扩张为主线的景观演化轨迹和生境质量不断退化的发展趋势。     

Membrane dynamics and the biogenesis of lysosomes (Review)

Lysosomes are dynamic organelles receiving membrane traffic input from the biosynthetic, endocytic and autophagic pathways. They may be regarded as storage organelles for acid hydrolases and are capable of fusing with late endosomes to form hybrid organelles where digestion of endocytosed macromolecules occurs. Reformation of lysosomes from the hybrid organelles involves content condensation and probably removal of some membrane proteins by vesicular traffic. Lysosomes can also fuse with the plasma membrane in response to cell surface damage and a rise in cytosolic Ca 2+ concentration. This process is important in plasma membrane repair. The molecular basis of membrane traffic pathways involving lysosomes is increasingly understood, in large part because of the identification of many proteins required for protein traffic to vacuoles in the yeast Saccharomyces cerevisiae. Mammalian orthologues of these proteins have been identified and studied in the processes of vesicular delivery of newly synthesized lysosomal proteins from the trans-Golgi network, fusion of lysosomes with late endosomes and sorting of membrane proteins into lumenal vesicles. Several multi-protein oligomeric complexes required for these processes have been identified. The present review focuses on current understanding of the molecular mechanisms of fusion of lysosomes with both endosomes and the plasma membrane and on the sorting events required for delivery of newly synthesized membrane proteins, endocytosed membrane proteins and other endocytosed macromolecules to lysosomes.     

Initial evaluation and follow-up of acute radiation syndrome in two patients from the Dakar accident

The aim of this work was to evaluate and follow up the evolution of radiation damage in two victims of a radiation accident. Blood samples were used for cytogenetic evaluation of radiation dose and heterogeneity. The radiation dose estimates were 1 Gy and 2.3 Gy in the two most exposed patients. Plasma was used for the measurement of the Flt3 ligand as a marker of haematopoietic aplasia, citrulline for damage to the jejunal mucosal epithelium and oxysterols for damage to the liver, the central nervous system and the vascular compartment. The use of these biological indicators demonstrated the presence of a haematopoietic syndrome and suggested the presence of subclinical radiation-induced damage to the liver in one of the two patients. These results support the interest in using these biological indicators in order to evaluate radiation damage, especially in complex accidental situations.     

A Kinase Inhibitor Screen Reveals Protein Kinase C-dependent Endocytic Recycling of ErbB2 in Breast Cancer Cells

ErbB2 overexpression drives oncogenesis in 20–30% cases of breast cancer. Oncogenic potential of ErbB2 is linked to inefficient endocytic traffic into lysosomes and preferential recycling. However, regulation of ErbB2 recycling is incompletely understood. We used a high-content immunofluorescence imaging-based kinase inhibitor screen on SKBR-3 breast cancer cells to identify kinases whose inhibition alters the clearance of cell surface ErbB2 induced by Hsp90 inhibitor 17-AAG. Less ErbB2 clearance was observed with broad-spectrum PKC inhibitor Ro 31-8220. A similar effect was observed with Go 6976, a selective inhibitor of classical Ca²⁺-dependent PKCs (α, β1, βII, and γ). PKC activation by PMA promoted surface ErbB2 clearance but without degradation, and ErbB2 was observed to move into a juxtanuclear compartment where it colocalized with PKC-α and PKC-δ together with the endocytic recycling regulator Arf6. PKC-α knockdown impaired the juxtanuclear localization of ErbB2. ErbB2 transit to the recycling compartment was also impaired upon PKC-δ knockdown. PMA-induced Erk phosphorylation was reduced by ErbB2 inhibitor lapatinib, as well as by knockdown of PKC-δ but not that of PKC-α. Our results suggest that activation of PKC-α and -δ mediates a novel positive feedback loop by promoting ErbB2 entry into the endocytic recycling compartment, consistent with reported positive roles for these PKCs in ErbB2-mediated tumorigenesis. As the endocytic recycling compartment/pericentrion has emerged as a PKC-dependent signaling hub for G-protein-coupled receptors, our findings raise the possibility that oncogenesis by ErbB2 involves previously unexplored PKC-dependent endosomal signaling.     

Mechanism and structure of the bacterial type IV secretion systems

The bacterial type IV secretion systems (T4SSs) translocate DNA and protein substrates to bacterial or eukaryotic target cells generally by a mechanism dependent on direct cell-to-cell contact. The T4SSs encompass two large subfamilies, the conjugation systems and the effector translocators. The conjugation systems mediate interbacterial DNA transfer and are responsible for the rapid dissemination of antibiotic resistance genes and virulence determinants in clinical settings. The effector translocators are used by many Gram-negative bacterial pathogens for delivery of potentially hundreds of virulence proteins to eukaryotic cells for modulation of different physiological processes during infection. Recently, there has been considerable progress in defining the structures of T4SS machine subunits and large machine subassemblies. Additionally, the nature of substrate translocation sequences and the contributions of accessory proteins to substrate docking with the translocation channel have been elucidated. A DNA translocation route through the Agrobacterium tumefaciens VirB/VirD4 system was defined, and both intracellular (DNA ligand, ATP energy) and extracellular (phage binding) signals were shown to activate type IV-dependent translocation. Finally, phylogenetic studies have shed light on the evolution and distribution of T4SSs, and complementary structure-function studies of diverse systems have identified adaptations tailored for novel functions in pathogenic settings. This review summarizes the recent progress in our understanding of the architecture and mechanism of action of these fascinating machines, with emphasis on the ‘archetypal’ A. tumefaciens VirB/VirD4 T4SS and related conjugation systems. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.     

Performance analysis of buffer allocation schemes under MMPP and Poisson traffic with individual thresholds

Various buffer management and congestion control mechanisms have been proposed to support differentiated Quality-of-Service (QoS) requirements due to the heterogeneous properties of real-world network traffic and applications. Active Queue Management (AQM) with multiple thresholds, which starts dropping packets before the queue becomes full in order to notify incipient stages of congestion, is a promising buffer allocation mechanism. With the aim to capture the effects of heterogeneous traffic and justify the choice of appropriate parameters, this paper develops an original analytical model for a finite buffer queueing system with AQM under two heterogeneous classes of traffic which are modelled, respectively, by the non-bursty Poisson Process and bursty Markov-Modulated Poisson Process (MMPP). We derive the aggregated and marginal performance metrics including the mean queue length, response time, utilization, throughput, and loss probability. Extensive simulation experiments are used to validate the accuracy of the analytical model. Furthermore the model is adopted to evaluate the performance of AQM with heterogeneous traffic and under different working conditions.

Atorvastatin partially prevents an inflammatory barrier breakdown of cultured human brain endothelial cells at a pharmacologically relevant concentration

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (i.e. statins) are currently under clinical investigation as a prophylactic immunomodulatory treatment for neurological diseases where an inflammatory disruption of the blood-brain barrier plays a pathogenic role. Here, we investigated whether atorvastatin pre-treatment modulates inflammatory-induced barrier dysfunction of cultured human brain microvascular endothelial cells (HBMEC). Pre-treatment of immortalized HBMEC with atorvastatin (50 nmol/L to 1 micromol/L) dose-dependently prevented an inflammatory up-regulation of monocyte chemoattractant protein-1/CCL2 but not of interleukin-8/CXCL8 and intercellular adhesion molecule-1 expression by tumor necrosis factor-alpha or interleukin-1beta. It antagonized an inflammatory up-regulation of claudin-3 expression while zonula occludens-1 and occludin protein levels remained unaltered. Like immortalized HBMEC, primary HBMEC also showed a reduction of claudin-3 and of inducible CCL2 expression following atorvastatin pre-treatment. On a functional level, atorvastatin pre-treatment of HBMEC strongly and dose-dependently reduced adhesion of activated T lymphocytes to pre-activated primary endothelium. Atorvastatin effects could partially be abolished by parallel mevalonate treatment. These anti-inflammatory effects of atorvastatin were observed already at a pharmacologically relevant concentration of 50 nmol/L. Our results obtained with human brain endothelial cells demonstrate how statins may partially prevent an inflammatory-mediated blood-brain barrier breakdown in humans.     

机动车驾驶员肇事认定研究进展

通常通过询问当事人、证人、调取现场监控录像等手段,就可以认定肇事的机动车驾驶员。但这些手段无法确定时,就需要通过鉴定来认定肇事的机动车驾驶员。目前,主要是从法医损伤学、计算机仿真模拟机动车碰撞过程并辅助法医学鉴定、对事故现场、车辆、衣着、人体等要素之间的关联性和动态性分析综合认定等角度鉴定肇事的机动车驾驶员。本文综述从以上三种角度鉴定肇事的机动车驾驶员的最新研究进展,并对认定肇事机动车驾驶员进行了展望。     

道路交通事故所致骨折特点、致伤机制及其与交通方式关系的研究

研究道路交通事故所致骨折的流行病学特点、骨折的特征及致伤机制;探讨交通方式与骨折的关系及其法医学意义,为预防、控制道路交通事故、交通伤骨折的急救及法医学的鉴定提供重要的依据.本文对2004年昆明市道路交通事故所致骨折518例临床法医鉴定及199例法医病理检验鉴定资料进行系统性分析研究.2005年及2006年.全国与云南省的交通事故数量下降趋势明显.交通事故所致骨折有以下特点:(1)多处、多发性骨折常见;(2)骨折部位呈"离心性分布";(3)暴力传导性骨折明显;(4)骨折刨伤严重,粉碎性及开放性骨折多见,多数需手术治疗;(5)下肢骨折常见,胫腓骨是下肢骨折最常见的部位;(6)四肢多发骨折常发生同侧肢体,摩托车、电动车、自行车驾驶员及乘员和行人发生四肢骨折时以同侧肢体多见,机动车驾驶员及机动车乘员以异侧肢体多见.骨折损伤方式以碰撞为主,其次是摔跌.