同型半胱氨酸化与疾病

高同型半胱氨酸血症能引起多种疾病如动脉粥样硬化、恶性肿瘤、神经退行性疾病等。研究发现,同型半胱氨酸(homocysteine,Hcy)能诱导氧化应激、内质网应激、蛋白质聚集。然而,具体的分子机制还有待进一步研究。近年来,蛋白质的同型半胱氨酸化引起广泛关注,本文对Hcy的代谢途径、同型半胱氨酸化及对机体的影响予以综述。     

辽河三角洲滨海湿地景观规划各预案对指示物种生态承载力的影响

在对辽河三角洲滨海湿地进行景观规划"预案”设计以及相应的生境分析基础上,运用景观生态决策与评价支持系统(LEDESS-model)对指示物种丹顶鹤和黑嘴鸥繁殖生境的生态承载力进行了空间模拟和定量分析,结果表明在大规模农业开发的背景下,预案A通过湿地调整及生境补偿措施,不仅可以维持湿地生境面积"无净损失”(No-net-loss),而且可以相当程度地提高指示物种繁殖生境的生态承载力;预案B通过一系列减轻生境破碎化影响的生境管理措施,也显著地提高了丹顶鹤繁殖生境的生态承载力,但对黑嘴鸥繁殖生境的生态承载力的改善不如前者显著;预案C的模拟结果说明采取"滚动”开发模式,可以有效减轻区域农业开发对物种生境的负面影响,在本研究限定的开发规模下(8000hm2),对指示物种丹顶鹤、黑嘴鸥繁殖生境的生态承载力没有明显影响.     

Identification of Arabidopsis rat mutants

Limited knowledge currently exists regarding the roles of plant genes and proteins in the Agrobacterium tumefaciens-mediated transformation process. To understand the host contribution to transformation, we carried out root-based transformation assays to identify Arabidopsis mutants that are resistant to Agrobacterium transformation (rat mutants). To date, we have identified 126 rat mutants by screening libraries of T-DNA insertion mutants and by using various “reverse genetic” approaches. These mutants disrupt expression of genes of numerous categories, including chromatin structural and remodeling genes, and genes encoding proteins implicated in nuclear targeting, cell wall structure and metabolism, cytoskeleton structure and function, and signal transduction. Here, we present an update on the identification and characterization of these rat mutants.     

细胞信号网络功能鲁棒的简并性拓扑特征

细胞信号网络对于外界环境的干扰表现出优良的鲁棒性,但是其维持功能鲁棒的内在机制尚未明确,本文研究了细胞信号网络功能鲁棒性的拓扑特征。选择布尔网络模型模拟细胞网络的动态行为,利用网络节点状态的扰动模拟外界环境干扰。基于演化策略探寻不同网络拓扑的功能并分析其在干扰环境下的鲁棒性,采用埃德尔曼提出的基于信息论的计算方法评估网络拓扑的简并度、冗余度和复杂度等拓扑属性,对比分析它们与功能鲁棒度的相关性及作用机理。结果显示,在网络模型的演化过程中,其拓扑简并度与功能鲁棒度显著正相关,相关性水平高于拓扑冗余度与鲁棒度的相关性。并且,随着鲁棒度的提升,网络的节点数和复杂度也随之升高,同样简并度与网络的节点数和复杂度的相关性高于拓扑冗余度与网络的节点数和复杂度的相关性。这说明增加的网络节点以简并的方式同时提高了网络拓扑的鲁棒度和复杂度。因此,细胞网络功能鲁棒性的拓扑特征是简并而不是冗余,简并为解决生物系统的复杂问题提供了有效手段,为人工系统的可靠性设计提供有益的借鉴。     

PK-15细胞微载体悬浮培养生产猪细小病毒的工艺研究

通过对猪细小病毒接毒时间TOI、MOI和收毒时间进行优化,开发了一种基于PK-15细胞静置培养的猪细小病毒生产工艺,最大病毒滴度达到107.5TCID50/ml。通过进一步优化接毒时间,成功建立了基于PK-15细胞反应器微载体悬浮培养的猪细小病毒培养工艺,在5L反应器上最大病毒滴度达到107.2TCID50/ml。首次发现乳酸对葡萄糖得率与病毒滴度的正相关性,当猪细小病毒滴度处于最大值时,乳酸对葡萄糖得率也达到最大值,可作为指针病毒滴度及收毒时间的重要参数。     

Targeted Next-Generation Sequencing in Uyghur Families with Non-Syndromic Sensorineural Hearing Loss

The mutation spectrum of deafness genes may vary in different ethnical groups. In this study, we investigated the genetic etiology of nonsyndromic deafness in four consanguineous and two multiplex Uyghur families in which mutations in common deafness genes GJB2, SLC26A4 and MT-RNR1 were excluded. Targeted next-generation sequencing of 97 deafness genes was performed in the probands of each family. Novel pathogenic mutations were identified in four probands including the p.L416R/p.A438T compound heterozygous mutations in TMC1, the homozygous p.V1880E mutation in MYO7A, c.1238delT frameshifting deletion in PCDH15 and c.9690+1G>A splice site mutation in MYO15A. Co-segregation of the mutations and the deafness were confirmed within each family by Sanger sequencing. No pathogenic mutations were identified in one multiplex family and one consanguineous family. Our study provided a useful piece of information for the genetic etiology of deafness in Uyghurs.     

Phylogenetic and Evolutionary Analyses of the Frizzled Gene Family in Common Carp (Cyprinus carpio) Provide Insights into Gene Expansion from Whole-Genome Duplications

In humans, the frizzled (FZD) gene family encodes 10 homologous proteins that commonly localize to the plasma membrane. Besides being associated with three main signaling pathways for cell development, most FZDs have different physiological effects and are major determinants in the development process of vertebrates and. Here, we identified and annotated the FZD genes in the whole-genome of common carp (Cyprinus carpio), a teleost fish, and determined their phylogenetic relationships to FZDs in other vertebrates. Our analyses revealed extensive gene duplications in the common carp that have led to the 26 FZD genes that we detected in the common carp genome. All 26 FZD genes were assigned orthology to the 10 FZD genes of on-land vertebrates, with none of genes being specific to the fish lineage. We postulated that the expansion of the FZD gene family in common carp was the result of an additional whole genome duplication event and that the FZD gene family in other teleosts has been lost in their evolution history with the reason that the functions of genes are redundant and conservation. Through the expression profiling of FZD genes in common carp, we speculate that the ancestral gene was likely capable of performing all functions and was expressed broadly, while some descendant duplicate genes only performed partial functions and were specifically expressed at certain stages of development.     

Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.