Dimerization of SLX4 contributes to functioning of the SLX4-nuclease complex

The Fanconi anemia protein SLX4 assembles a genome and telomere maintenance toolkit, consisting of the nucleases SLX1, MUS81 and XPF. Although it is known that SLX4 acts as a scaffold for building this complex, the molecular basis underlying this function of SLX4 remains unclear. Here, we report that functioning of SLX4 is dependent on its dimerization via an oligomerization motif called the BTB domain. We solved the crystal structure of the SLX4_BTB dimer, identifying key contacts (F681 and F708) that mediate dimerization. Disruption of BTB dimerization abrogates nuclear foci formation and telomeric localization of not only SLX4 but also of its associated nucleases. Furthermore, dimerization-deficient SLX4 mutants cause defective cellular response to DNA interstrand crosslinking agent and telomere maintenance, underscoring the contribution of BTB domain-mediated dimerization of SLX4 in genome and telomere maintenance.     

Comparative Microarray Analysis Identifies Commonalities in Neuronal Injury: Evidence for Oxidative Stress,Dysfunction of Calcium Signalling,and Inhibition of Autophagy–Lysosomal Pathway

Mitochondrial dysfunction, ubiquitin-proteasomal system impairment and excitotoxicity occur during the injury and death of neurons in neurodegenerative conditions. The aim of this work was to elucidate the cellular mechanisms that are universally altered by these conditions. Through overlapping expression profiles of rotenone-, lactacystin- and N-methyl-d-aspartate-treated cortical neurons, we have identified three affected biological processes that are commonly affected; oxidative stress, dysfunction of calcium signalling and inhibition of the autophagic–lysosomal pathway. These data provides many opportunities for therapeutic intervention in neurodegenerative conditions, where mitochondrial dysfunction, proteasomal inhibition and excitotoxicity are evident.     

Natural and engineered biosynthesis of nucleoside antibiotics in Actinomycetes

Journal of Industrial Microbiology & Biotechnology - Nucleoside antibiotics constitute an important family of microbial natural products bearing diverse bioactivities and unusual structural...     

Secretory carrier membrane protein SCAMP2 and phosphatidylinositol 4,5-bisphosphate interactions in the regulation of dense core vesicle exocytosis

Secretory carrier membrane protein 2 (SCAMP2) functions in late steps of membrane fusion in calcium-dependent granule exocytosis. A basic/hydrophobic peptide segment within SCAMP2 (SCAMP2 E: CWYRPIYKAFR) has been implicated in this function and shown to bind and sequester phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 or PIP2] within membranes through an electrostatic mechanism. We now show that alanine substitution of tryptophan W2 within SCAMP2 E substantially weakens peptide binding to negatively charged liposomes; other substitutions for arginine R4 and lysine K8 have only limited effects on binding. Electron paramagnetic resonance analysis of liposomes containing spin-labeled PIP2 shows that R4 but not K8 is critical for SCAMP E binding to PIP2. The interfacial locations of SCAMP E and its structural variants within lipid bicelles measured by oxygen enhancement of nuclear relaxation are all similar. Corresponding point mutations within full-length SCAMP2 (SC2-R204A, SC2-K208A, and SC2-W202A) have been analyzed for biological effects on dense core vesicle exocytosis in neuroendocrine PC12 cells. With the same level of overexpression, SC2-R204A but not SC2-K208A inhibited secretion of cotransfected human growth hormone and of noradrenalin. Inhibition by SC2-R204A was the same as or greater than previously observed for SC2-W202A. Analysis of noradrenalin secretion by amperometry showed that inhibitory mutants of SCAMP2 decrease the probability of fusion pore opening and the stability of initially opened but not yet expanded fusion pores. The strong correlation between SCAMP2 E interactions with PIP2 and inhibition of exocytosis, particularly by SC2-R204A, led us to propose that SCAMP2 interaction with PIP2 within the membrane interface regulates fusion pore formation during exocytosis.     

HDJC9, a novel human type C DnaJ/HSP40 member interacts with and cochaperones HSP70 through the J domain

HSP40s are a subfamily of heat shock proteins (HSPs) and play important roles in regulation of cell proliferation, survival and apoptosis by serving as chaperones for HSP70s. Up to date hundreds of HSP40 proteins derived from various species ranging from Escherichia coli to homo sapiens have been identified. Here we report the cloning and characterization of a novel human type C DnaJ homologue, HDJC9, containing a typical N-terminal J domain. HDJC9 is upregulated at both mRNA and protein levels upon various stress and mitogenic stimulations. HDJC9 is mainly localized in cell nuclei under normal culture conditions while it is transported into cytoplasm and plasma membrane upon heat shock stress through a non-classical and lipid-dependent pathway. HDJC9 can interact with HSP70s and activate the ATPase activity of HSP70s, both of which are dependent on the J domain. Our data suggest that HDJC9 is a novel cochaperone for HSP70s.     

宽叶韭种内分化的同工酶及可溶性蛋白的研究

采用聚丙烯酰胺凝胶电泳（ＰＡＧＥ）对宽叶韭的３个代表居群内不同植株间的过氧化物酶、酯酶和１６个居群间的酯酶（ＥＳＴ）、过氧化物酶（ＰＯＸ）、葡萄糖－６－磷酸脱氢酶（Ｇ６ＰＤＨ）、苹果酸酶（ＭＥ）、苹果酸脱氢酶（ＭＤＨ）、天冬氨酸转移酶（ＡＡＴ）、腺苷三磷酸酶（ＡＴＰａｓｅ）、乳酸脱氢酶（ＬＤＨ）８种同工酶系统以及可溶性蛋白进行了分析。结果发现：居群内不同植株的酶谱无差异;居群间的酶谱存在多态性,酶谱差异明显,且各居群均有其特征酶谱。采用“排序”方法和聚类分析,对宽叶韭１６个居群酶谱的相似系数和酶谱距离进行了研究。同工酶谱表型差异彼此显著的３个代表居群的可溶性蛋白双向电泳图谱也表现出明显差异,印证了同工酶的分析结果。结合细胞学的最新核型证据,从生物化学角度确定了这１６个居群间的亲缘关系和彼此的分化程度。结果表明：宽叶韭明显分为两大类,即冬季不倒苗和冬季倒苗两类,在同一类型中各居群之间彼此近缘,且冬季不倒苗的类型分化程度较高。本研究首次将多种同工酶的综合分析与聚类分析及可溶性蛋白双向电泳用于葱属植物的种内分化研究,为植物分子进化和系统学研究提供了科学依据     

漆树胚,胚乳发育及花果生长的相关性研究

漆树为倒生胚珠,双珠被,厚珠心,具承珠盘及拟珠孔塞,胚囊发育为蓼型,核型胚乳,胚发育为柳叶菜型,后历经棒状形胚、心形胚、鱼雷形胚和成熟胚各期。花和果实生长与胚及胚乳发育有密切的相关性,胚内具原始的乳汁道系统为重要特征。一些胚珠内无胚或胚乳早期退化引起胚败育是造成种子空籽原因之一。     

纳络酮对东方蝾螈胚胎表皮传导的阻断作用

在胚胎发育的一定时期,表皮细胞呈现较强的β-内啡肽阳性免疫反应,而这时期正是表皮传导最活跃的时期。为了探索胚胎表皮传导和β-内啡肽-类阿片样多肽之间是否有关系,本实验采用纳络酮处理,发现表皮传导消失,待纳络酮作用消除后,表皮传导现象又再出现,说明纳络酮在胚胎表皮细胞传导中起了阻断的作用。     

A survey of genes in Eimeria tenella merozoites by EST sequencing

A study of about 500 expressed sequence tags (ESTs), derived from a merozoite cDNA library, was initiated as an approach to generate a larger pool of gene information on Eimeria tenella. Of the ESTs, 47.7% had matches with entries in the databases, including ribosomal proteins, metabolic enzymes and proteins with other functions, of which 14.3% represented previously known E. tenella genes. Thus over 50% of the ESTs had no significant database matches. The E. tenella EST dataset contained a range of highly abundant genes comparable with that found in the EST dataset of T. gondii and may thus reflect the importance of such molecules in the biology of the apicomplexan organisms. However, comparison of the two datasets revealed very few homologies between sequences of apical organelle molecules, and provides evidence for sequence divergence between these closely-related parasites. The data presented underpin the potential value of the EST strategy for the discovery of novel genes and may allow for a more rapid increase in the knowledge and understanding of gene expression in the merozoite life cycle stage of Eimeria spp.     

Discovery of Algal Fossils from the Hailar Basin and Its Significance

This article reports Chlorococcalean algae fossil in Member 2 of Damoguaihe Formation, Well Haican-5, South of Hailar Basin. They are Pediastrum simplex, P. boryanum, Scenedesmus cf. bijuga, S. cf. dimorphus, S. beierensis sp. nov.