Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets

Understanding the neuropathology of multiple sclerosis (MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser-capture microdissection and proteomics, proteins unique to three major types of MS lesions: acute plaque, chronic active plaque and chronic plaque. Comparative proteomic profiles identified tissue factor and protein C inhibitor within chronic active plaque samples, suggesting dysregulation of molecules associated with coagulation. In vivo administration of hirudin or recombinant activated protein C reduced disease severity in experimental autoimmune encephalomyelitis and suppressed Th1 and Th17 cytokines in astrocytes and immune cells. Administration of mutant forms of recombinant activated protein C showed that both its anticoagulant and its signalling functions were essential for optimal amelioration of experimental autoimmune encephalomyelitis. A proteomic approach illuminated potential therapeutic targets selective for specific pathological stages of MS and implicated participation of the coagulation cascade.     

A BAC clone of MDV strain GX0101 with REV-LTR integration retained its pathogenicity

The complete genome of Marek＇s disease virus （MDV） strain GX0101, which was integrated with the LTR sequences of REV, was cloned in Escherichia coli as a bacterial artificial chromosome （BAC）. BAC vector sequences were introduced into the US2 locus of the MDV genome by homologous recombination. The viral DNA containing the BAC vector was used to transform Escherichia coli strain of DH10B. Then the recombinant virus was successfully rescued by transfection of the recombinant BAC DNA into primary chicken embryo fibroblast （CEF）. This BAC viral clone was named bac-GX0101. When the reconstituted virus was inoculated into 1-day-old birds, visceral tumors could be detected as early as 62 d post infection. There was no difference in growth ability and pathogenicity to birds between the BAC derived virus and its parental virus. The BAC derived virus maintained its oncogenicity and immunosuppressive effects. In conclusion, the complete genome of GX0101 strain was successfully cloned into BAC and the infectious clone was rescued. With the powerful BAC manipulation system, the infectious clone will provide a useful tool for further understanding the functional roles of the inserted REV-LTR sequence in the GX0101 strain of MDV,     

Degeneration under the Microscope at the fin se siècle

Theories of familial, racial, and national degeneration in the late nineteenth and early twentieth centuries have been explored by historians in the context of social and moral pathology. At the same time nerve degeneration was studied in the post mortem room and in the laboratory but links to the broader ideology of degeneration have not been investigated by scholars. This paper joins these domains by examining the concept of Wallerian degeneration. It argues that various discourses—including those of the laboratory scientist, the clinician, and the social theorist—employed the term degeneration, and these discourses frequently overlapped demonstrating that degeneration was a ubiquitous fact of Victorian and Edwardian nature.     

Megadrought and cultural exchange along the proto-silk road

Arid Central Asia(ACA),with its diverse landscapes of high mountains,oases,and deserts,hosted the cen-tral routes of the Silk Roads that linked trade centers fr...     

带有REV-LTR片段的MDV野毒株GX0101 BAC克隆的构建及拯救病毒的致病性分析

将整合有禽网状内皮组织增生症病毒(reticuloendotheliosis, REV)长末端重复序列(LTR)的马立克氏病病毒(命名为GX0101)全基因组作为细菌人工染色体(bacterial artificial chromosome, BAC)克隆进大肠杆菌. BAC载体通过同源重组插入MDV基因组的US2区, 含BAC载体的MDV DNA电转化大肠杆菌菌株DH10B, 鉴定含MDV全基因组的BAC克隆(MDV BAC), 提取BAC DNA, 转染原代鸡胚成纤维细胞(CEF), 成功拯救出了重组病毒, 命名为bac-GX0101. 将此病毒腹腔接种1日龄鸡, 在攻毒后62 d开始检测到内脏肿瘤, 动物实验结果表明, bac-GX0101毒株与亲本GX0101毒株对机体的致病性等方面的影响没有差异, bac-GX0101毒株仍然保留着很好的免疫抑制功能及致肿瘤能力. 该感染性克隆bac-GX0101为研究该重组野毒株中REV-LTR插入片段及其他基因的生物学功能提供了有用的技术平台.