c-Ski/SnoN与肾间质纤维化

c-Ski／SnoN是由原癌基因c-ski／sno编码的核蛋白,属于Ski家族成员。近年来有研究表明c-Ski／SnoN是TGF-β1／Smad信号通路的重要负性调控因子,通过与Smad蛋白相互作用来抑制TGF-β1靶基因的活化。本文就c-Ski／SnoN对TGF-β1／Smad信号通路的调节作用,以及在肾间质纤维化的发生发展中的作用及机制作一综述。     

The complete nucleotide sequence of the mitochondrial genome of Tetraodon nigroviridis.

The fresh water pufferfish Tetraodon nigroviridis is a model organism for studying evolution of genome and gene functions, but its mitochondrial genome (mtDNA) sequence is still not available. We determined the complete nucleotide sequence of its mtDNA using shotgun sequencing. The T. nigroviridis mtDNA was 16,462 bp, and contained 13 protein coding genes, 22 tRNAs, 2 rRNAs and a major non-coding region. The gene order was identical to the common type of vertebrate mtDNA, whereas the G + C content in the sense strand was 46.9%, much higher than most other fish species. One hundred and three SNPs were detected in the control region of the mtDNA of 35 individuals, a majority of SNPs were detected in the 5' end of the control region. A phylogenetic study including 21 fish species was performed on concatenated amino acid sequences of 12 protein coding genes, and revealed that the T. nigroviridis was clustered with Fugu rubripes into a group. The complete mtDNA sequence and SNPs in its control region will be useful in studying fish evolution, in differentiating different Tetraodon species and in analyzing genetic diversity within T. nigroviridis.     

Targeted regulation of FoxO1 in chondrocytes prevents age‐related osteoarthritis via autophagy mechanism

Autophagy is designated as a biological recycling process to maintain cellular homeostasis by the sequestration of damaged proteins and organelles in plasma and cargo delivery to lysosomes for degradation and reclamation. This organelle recycling process promotes chondrocyte homeostasis and has been previously implicated in osteoarthritis (OA). Autophagy is widely involved in regulating chondrocyte degeneration markers such as MMPs, ADAMSTs and Col10 in chondrocytes. The critical autophagy‐related (ATG) proteins have now been considered the protective factor against late‐onset OA. The current research field proposes that the autophagic pathway is closely related to chondrocyte activity. However, the mechanism is complex yet needs precise elaboration. This review concluded that FoxO1, a forkhead O family protein, which is a decisive mediator of autophagy, facilitates the pathological process of osteoarthritis. Diverse mechanisms regulate the activity of FoxO1 and promote the initiation of autophagy, including the prominent AMPK and Sirt‐2 cellular pathways. FoxO1 transactive is regulated by phosphorylation and acetylation processes, which modulates the downstream ATGs expression. Furthermore, FoxO1 induces autophagy by directly interacting with ATGs proteins, which control the formation of autophagosomes and lysosomes fusion. This review will discuss cutting‐edge evidence that the FoxO–autophagy pathway plays an essential regulator in the pathogenesis of osteoarthritis.     

HCV全长NS3基因表达及在抗体检测中的应用

丙型肝炎病毒 (ＨＣＶ)是引起非甲非乙型肝炎的主要病原因子。被ＨＣＶ感染的病例中 ,超过 5 0 %以上会引起持续性感染、慢性肝炎 ,最终可能引起肝硬化和肝细胞癌[1] 。ＨＣＶ严重威胁人类健康 ,但目前对丙肝患者尚缺乏有效的治疗手段 ,因此 ,严格把好血源关 ,提高对丙肝患者检出的灵敏度 ,是阻止丙肝血源传播的有效手段。丙型肝炎病毒基因组为单股正链ＲＮＡ ,核苷酸长约 9.5ｋｂ ,仅含一个开放阅读框 ,翻译成一个大的聚蛋白前体 ,由宿主细胞信号肽酶和病毒蛋白酶加工成多个成熟蛋白。其中非结构蛋白ＮＳ3分子量为 70ｋＤ ,有丝氨酸蛋白酶…     

Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily

4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase catalyzes a complex rearrangement of 5-aminoimidazole ribonucleotide (AIR) to form HMP-P, the pyrimidine moiety of thiamine phosphate. We determined the three-dimensional structures of HMP-P synthase and its complexes with the product HMP-P and a substrate analog imidazole ribotide. The structure of HMP-P synthase reveals a homodimer in which each protomer comprises three domains: an N-terminal domain with a novel fold, a central (betaalpha)(8) barrel and a disordered C-terminal domain that contains a conserved CX(2)CX(4)C motif, which is suggestive of a [4Fe-4S] cluster. Biochemical studies have confirmed that HMP-P synthase is iron sulfur cluster-dependent, that it is a new member of the radical SAM superfamily and that HMP-P and 5'-deoxyadenosine are products of the reaction. M?ssbauer and EPR spectroscopy confirm the presence of one [4Fe-4S] cluster. Structural comparisons reveal that HMP-P synthase is homologous to a group of adenosylcobalamin radical enzymes. This similarity supports an evolutionary relationship between these two superfamilies.     

黑龙江省部分地区非综合性耳聋的分子病因学调查

目的:采用基因诊断的方法调查和分析黑龙江省部分地区非综合性耳聋(NSHL)的分子病因学。方法:调查对象为哈尔滨医科大学附属第四医院耳鼻咽喉科门诊收治的116例来自黑龙江省部分地区的散发非综合征型耳聋患者和29例听力正常样本,均经过纯音听阈、声导抗、耳声发射、听性脑干诱发电位等检查,其中51例属于重度或极重度感音神经性耳聋,采集其外周血并提取DNA行GJB2、Slc26A4、GJB3、SrRNA1555基因编码区测序。结果:与耳聋相关的基因突变位点主要为GJB2-235、Slc26A4-IVS7-2和GJB2-299,其中GJB2-235基因变异为最主要方式,约占总检出耳聋患者的45.2%,其次为该基因的299位点,突变比率为16.1%。另一个主要突变基因是Slc26A4,主要在IVS7-2位点发生突变,约占Slc26A4基因位点突变的84.6%,在整个耳聋基因突变群体中约占17.7%。但上述基因突变位点在29例听力正常样本中无发生。结论:黑龙江省部分地区NSHL患者存在GJB2-235、Slc26A4-IVS7-2和GJB2-299位点突变。     

基于多尺度协同的长沙市生态网络构建与层级优化

城市化背景下人类与自然环境的矛盾呈现出多尺度、层级化特征,而传统生态网络的构建方式较少考虑不同尺度下生态要素的关系,无法从区域落实到中心城区,难以形成系统性的解决方案。研究在综合梳理各尺度生态网络构建方法的基础上,以长沙市为例,基于形态学空间格局分析（Morphological Spatial Pattern Analysis,MSPA）、景观连通性原理和生态斑块重要性评价识别生态源地,并通过多层级生态阻力面的确定,综合运用最小费用路径（Least-cost path method,LCP）、电路理论、层级传导理论、尺度嵌套等方法对市域、都市区、中心城区的生态网络进行了协同构建和层级优化,最后基于不同尺度生态网络的特点应用并落实到多层级的国土空间规划体系中。研究结果表明：（1）长沙市域生态网络和都市区生态网络具有较好的层级嵌套特征;共识别两尺度生态叠合源地14个、生态叠合廊道15条,主要通过中心城区内的湘江、浏阳河和捞刀河部分河段与外围生态绿圈相衔接,形成"外环内楔"的空间格局。（2）确定市域重要廊道、市域潜在廊道、生态叠合廊道、都市区重要廊道、都市区潜在廊道的核心保护面积共501.14 km²,并提取位于生态廊道核心保护区范围内的生态夹点和生态障碍点,以进一步落实生态保护修复策略。（3）得到具有重要生态连通功能的中心城区生态绿道长度441.2 km,生态修复单元56个,并结合生态阻力值划分为5级进行针对性修复。（4）基于不同尺度生态网络的衔接、嵌套,最终构建"市域总体生态安全格局-都市区城市生态空间发展格局-以城市绿道为基础的中心城区生态修复单元",并与不同层级的国土空间规划体系相对应。研究结果将为以大城市为中心的跨尺度生态系统修复和生态安全格局构建提供科学参考。     

罗霄山脉翼手目物种多样性及适生区预测

罗霄山脉位于中国大陆东南部, 是一条南北走向的大型山脉, 面积约6.76万km²。该山脉位于欧亚大陆东部季风区, 生物多样性丰富, 是亚洲东部第三纪冰期动物重要的避难所。为了解罗霄山脉翼手目物种多样性状况, 本研究组于2013-2018年, 使用雾网、手网和竖琴网等工具开展了针对性调查与标本采集, 同时运用形态分类学和分子系统发生学方法鉴定物种。根据调查结果并结合文献记载: 罗霄山脉地区现有翼手目物种4科14属40种, 其中罗霄山脉翼手目新记录种25种, 省级翼手目分布新记录种9种。同时, 本研究基于5年的调查采集位点, 使用生物多样 性与气候变化虚拟实验室(the Biodiversity & Climate Change Virtual Laboratory)在线生境预测平台, 对罗霄山脉翼手目物种当前的适生区, 以及3种不同量温室气体排放情景下(representative concentration pathway, RCP 2.6 / 6.0 / 8.5) 2050年的适生区进行预测, 其中随机森林算法(random forest)的模型解释力较优, 其预测结果显示: 影响该区域翼手目分布的主要环境因子为降水季节性和年平均温度; 山脉中部及南部为翼手目的高适生区, 面积约为罗霄山脉的30%; 与当前适生区相比, RCP 2.6情景下2050年该类群适生区有所扩增, RCP 6.0和RCP 8.5情景下均会导致翼手目适生区急剧缩减, 且分布区将迁移至高海拔区域以响应气候变化。而本项目的开展不仅初步掌握了罗霄山脉翼手目物种多样性本底状况, 也为开展后续的翼手目研究和保护管理提供了参考。     

沙漠腹地天然绿洲胡杨和柽柳叶片δ13C值对不同地下水埋深的响应

干旱区植物的水分利用效率对植物的分布及水分利用状况具有重要意义。基于不同地下水埋深条件下沙漠腹地绿洲优势种胡杨和柽柳叶片δ¹³C值,分析了胡杨和柽柳的水分利用效率对不同地下水埋深的响应。结果表明: 随着地下水埋深由2.1 m增加到4.3 m,柽柳叶片的δ¹³C值先略有增加后处于较为稳定状态,柽柳采取较为稳定的水分利用效率适应干旱环境;胡杨叶片的δ¹³C值呈现先略有减小后增加的趋势,胡杨通过提高水分利用效率的策略适应干旱胁迫。同一地下水埋深条件下柽柳叶片的δ¹³C值高于胡杨叶片,表明柽柳的水分利用效率高于胡杨。