Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease)

"Lysosomal glycogen storage disease with normal acid maltase" which was originally described by Danon et al., is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. Here we report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease. To our knowledge this is the first example of human cardiopathy-myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.     

Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice

The mouse mutant mnd2 (motor neuron degeneration 2) exhibits muscle wasting, neurodegeneration, involution of the spleen and thymus, and death by 40 days of age. Degeneration of striatal neurons, with astrogliosis and microglia activation, begins at around 3 weeks of age, and other neurons are affected at later stages. Here we have identified the mnd2 mutation as the missense mutation Ser276Cys in the protease domain of the nuclear-encoded mitochondrial serine protease Omi (also known as HtrA2 or Prss25). Protease activity of Omi is greatly reduced in tissues of mnd2 mice but is restored in mice rescued by a bacterial artificial chromosome transgene containing the wild-type Omi gene. Deletion of the PDZ domain partially restores protease activity to the inactive recombinant Omi protein carrying the Ser276Cys mutation, suggesting that the mutation impairs substrate access or binding to the active site pocket. Loss of Omi protease activity increases the susceptibility of mitochondria to induction of the permeability transition, and increases the sensitivity of mouse embryonic fibroblasts to stress-induced cell death. The neurodegeneration and juvenile lethality in mnd2 mice result from this defect in mitochondrial Omi protease.     

油墨雾散的成因及消除方法探讨

油墨在墨辊间转移的过程中由于自身内聚力和静电力的作用有时会产生雾散现象,油墨的雾散现象是存在于高速印刷中的一大公害。本文仅从动力学角度对其产生的原因进行了初步分析,在此基础上对减少油墨的雾散的方法进行探讨。     

Application of phorbol ester to mouse skin causes a rapid and sustained loss of protein kinase C

It is now widely accepted that tumour-promoting phorbol esters activate a Ca2+- and phospholipid-dependent protein kinase (protein kinase C) both in vitro and in intact cells, and that the kinase represents a major cellular phorbol ester-binding protein. The phorbol esters act as analogues of diacylglycerol, a natural regulator of protein kinase C, and stabilize the membrane-association of the kinase. Although other molecular targets may exist, protein kinase C activation is probably important in mediating the diverse responses of cultured cells to phorbol esters and in promoting in vivo tumours. The enzyme comprises a family of closely related proteins and has been detected in extracts from mouse epidermal cells, the likely targets for two-stage carcinogenesis in mouse skin. In this report we show that application of a single dose of TPA (12-O-tetradecanoyl phorbol-13-acetate) to mouse skin results in a rapid and complete loss of protein kinase C activity which is maintained for 3-4 days. This is associated with a loss of immunologically detectable protein kinase C and the accumulation of a smaller protein detectable by antibodies recognizing the regulatory domain of protein kinase C.     

Regulation of cell cycle progression and gene expression by H2A deubiquitination

Post-translational histone modifications have important regulatory roles in chromatin structure and function. One example of such modifications is histone ubiquitination, which occurs predominately on histone H2A and H2B. Although the recent identification of the ubiquitin ligase for histone H2A has revealed important roles for H2A ubiquitination in Hox gene silencing as well as in X-chromosome inactivation, the enzyme(s) involved in H2A deubiquitination and the function of H2A deubiquitination are not known. Here we report the identification and functional characterization of the major deubiquitinase for histone H2A, Ubp-M (also called USP16). Ubp-M prefers nucleosomal substrates in vitro, and specifically deubiquitinates histone H2A but not H2B in vitro and in vivo. Notably, knockdown of Ubp-M in HeLa cells results in slow cell growth rates owing to defects in the mitotic phase of the cell cycle. Further studies reveal that H2A deubiquitination by Ubp-M is a prerequisite for subsequent phosphorylation of Ser 10 of H3 and chromosome segregation when cells enter mitosis. Furthermore, we demonstrate that Ubp-M regulates Hox gene expression through H2A deubiquitination and that blocking the function of Ubp-M results in defective posterior development in Xenopus laevis. This study identifies the major deubiquitinase for histone H2A and demonstrates that H2A deubiquitination is critically involved in cell cycle progression and gene expression.     

Molecular cloning and polymorphism of the human immune deficiency virus type 2

We recently reported the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of the AIDS epidemic now spreading in Central and East Africa, as well as the USA and Europe (see ref. 3 for review) both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. But preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1-positive sera. We now report the molecular cloning of the complete 9.5-kilobase (kb) genome of HIV-2, the observation of restriction site polymorphism between different isolates, and a preliminary analysis of the relationship of HIV-2 with other human and simian retroviruses.     

Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast

Cyclin-dependent kinases (CDKs) drive major cell cycle events including the initiation of chromosomal DNA replication. We identified two S phase CDK (S-CDK) phosphorylation sites in the budding yeast Sld3 protein that, together, are essential for DNA replication. Here we show that, when phosphorylated, these sites bind to the amino-terminal BRCT repeats of Dpb11. An Sld3-Dpb11 fusion construct bypasses the requirement for both Sld3 phosphorylation and the N-terminal BRCT repeats of Dpb11. Co-expression of this fusion with a phospho-mimicking mutant in a second essential CDK substrate, Sld2, promotes DNA replication in the absence of S-CDK. Therefore, Sld2 and Sld3 are the minimal set of S-CDK targets required for DNA replication. DNA replication in cells lacking G1 phase CDK (G1-CDK) required expression of the Cdc7 kinase regulatory subunit, Dbf4, as well as Sld2 and Sld3 bypass. Our results help to explain how G1- and S-CDKs promote DNA replication in yeast.     

茵陈蒿汤对肝纤维化大鼠Caspase-12通路以及TIMP-1、Smad2的影响

目的探究茵陈蒿汤对肝纤维化（LF）大鼠Caspase-12通路以及TIMP-1、Smad2的影响。方法雄性SD大鼠45只,随机分为3组,即对照组,模型组和茵陈蒿汤组。使用腹腔注射CCl 4 建立LF模型,茵陈蒿汤组在建模时使用茵陈蒿汤灌胃,持续8周。比较8周后各组大鼠的一般情况,分别使用HE染色和Masson染色观察肝组织形态和纤维化情况。分别使用Western blot和RT-qPCR检测蛋白和mRNA的水平。结果模型组大鼠出现明显的肝损伤和纤维化,茵陈蒿汤组大鼠肝损伤情况和纤维化情况显著减轻。血生化结果显示,模型组ALT和AST水平显著高于对照组（P <0. 05）,菌陈蒿汤干预后ALT和AST水平显著低于模型组,差异具有统计学意义（P <0. 05）。建模后8周模型组大鼠肝组织中GRP78、eIF2α和Caspase-12显著升高（P <0. 01）,茵陈蒿汤组的GRP78、eIF2α和Caspase-12显著低于模型组（P <0. 01）。模型组的Collagen Ⅰ、Collagen Ⅲ、TIMP-1、Smad2 mRNA和蛋白水平显著高于对照组（P <0. 01）,茵陈蒿汤组Collagen Ⅰ、Collagen Ⅲ、TIMP-1、Smad2 mRNA和蛋白水平显著低于模型组（P <0. 01）。结论茵陈蒿汤可显著缓解大鼠肝组织的纤维化,这可能由于茵陈蒿汤具有抑制Caspase-12通路以及Smad2基因的表达发挥抗纤维化和抗凋亡的作用有关。     

邯钢二炼钢厂板坯中心偏析的成因及对策

分析了邯钢二炼钢厂板坯中心偏析的成因。阐述了如何解决由其引起的铸坯质量问题,采取了如下措施:要求中间包钢水[S]<0.015％,[P]<0.015％;应用PHOENICS软件,优化了浸入式水口参数,在不增加专门的压下设备条件下,通过逐渐缩小二冷夹辊开口度,在铸坯凝固70％部位,加大夹辊加下量,实现了铸坯总压下4.5 mm的轻压下。     

邯钢二炼钢厂板坯中心偏析的成因及对策

分析了邯钢二炼钢厂板坯中心偏析的成因.阐述了如何解决由其引起的铸坯质量问题,采取了如下措施:要求中间包钢水[S]＜0.015%,[P]＜0.015%;应用PHOENICS软件,优化了浸入式水口参数,在不增加专门的压下设备条件下,通过逐渐缩小二冷夹辊开口度,在铸坯凝固70%部位,加大夹辊加下量,实现了铸坯总压下4.5 mm的轻压下.     

Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell

The mitogens which modulate cell-cell interactions during development of the central nervous system are unknown. One of the few interactions sufficiently well understood to allow identification of such molecules involves the two glial lineages which make up the rat optic nerve. One population of glial cells in this tissue, the type-1 astrocytes, secrete a soluble factor(s) which promotes division of a second population of bipotential oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells; these progenitors give rise to oligodendrocytes, which myelinate large axons in the CNS, and type-2 astrocytes, which enwrap bare axons at nodes of Ranvier. Type-1 astrocytes also promote progenitor motility, and inhibit the premature differentiation of progenitors into oligodendrocytes which occur when these cells are grown in the absence of type-1 astrocytes. We have now found that platelet-derived growth factor mimics the effects of type-1 astrocytes on O-2A progenitor cells, and antibodies to PDGF block the effects of type-1 astrocytes.     

快速凝固Al85Ni8Zr3Cu2Y2非晶材料的形成及热稳定性分析

采用旋铸急冷工艺分别在大气和真空环境中获得了Al85Ni10Zr5和Al85Ni8Zr3Cu2Y2韧性非晶合金带材,利用X射线衍射和示差扫描量热仪(DSC)对条带的显微结构及热稳定性进行了分析.结果表明,无论在真空还是在大气条件下,Y,Cu元素的添加都提高了Al85Ni10Zr5合金的非晶形成能力及热稳定性.研究发现,合金成分及冷却速率对非晶的形成起了重要作用,而甩带环境对Al Ni Zr合金系的非晶形成影响不大.     

不同时期肝硬化大鼠门静脉血与下腔静脉血中内源性硫化氢的比较

为观察H2S在不同时期肝硬化大鼠门静脉与下腔静脉血中浓度的变化,探索其在肝硬化发生发展过程中的作用.制备四氯化碳诱导的肝硬化大鼠模型,在第15d、第30d、第52d取大鼠门静脉及下腔静脉血检测H2S浓度.肝硬化早、中、晚期大鼠门静脉血和下腔静脉血中H2S的含量均显著低于正常对照组,且H2S浓度随着肝脏病变的加重而逐渐降低;在肝硬化中期及晚期,门静脉血中H2S的浓度明显低于下腔静脉.结果显示,实验性肝硬化大鼠门静脉血和下腔静脉血中H2S在肝硬化门脉高压高动力循环发生发展中起着重要作用.     

快淬速度对Nd2Fe14B/α-Fe纳米晶双相复合稀土永磁材料相结构和磁性能的影响

采用熔体快淬法在不同快淬速度下制备了Nd8Fe86B6合金中Nd2Fe14B/α-Fe双相复合纳米晶薄带．用X射线衍射仪（XRD）和振动样品磁强计（VSM）测量了薄带的相结构和磁性能．结果表明：Nd8Fe86B6合金的最佳快淬速度为18m/s，在此条件下制备的合金薄带平均晶粒尺寸细小．综合磁性能好；合金薄带的平均晶粒尺寸为24．4nm，磁性能为Br=0．69T。Br/Bs=0．66。Hc=296．1kA/m．     

A rapid and accurate 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay for quantification of bacteriocins with nisin as an example

The objective of this study is to propose a more accurate and faster MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] colorimetric assay (MCA) for quantitative measurement of polypeptide bacteriocins in solutions with nisin as an example. After an initial incubation of nisin and indicator bacterium Micrococcus luteus NCIB 8166 in tubes, MTT was added for another incubation period. After that, nisin was quantified by estimating the number of viable bacteria based on measuring the amount of purple formazan produced by cleavage of yellow tetrazolium salt MTT. Then MCA was compared to a standard agar diffusion assay (ADA). The results suggested a high correlation coefficient (r ²=0.975±0.004) between optical density (OD) and the inhibitory effect of nisin on a bacterial strain Micrococcus luteus NCIB 8166 at a range of 0.125~32 IU/ml. The MCA described in this study was very quick. Quantification of nisin took only 7~8 h and the detection limit was at the level of 0.125 IU/ml when compared to 12 IU/ml and 24~28 h for ADA. The MCA provides an accurate and rapid method for quantification of nisin in solutions and is expected to be used for quantification of other antimicrobial substances.     

摇摆钢支撑快速建筑信息模型建模技术及其Revit模块开发

近年来,由于政府引导和行业需求,建筑信息模型(building information modeling, BIM)技术及应用迅猛发展,已取得了良好的社会和经济效益。为了进一步拓展BIM在土木工程新技术中的应用,针对新型摇摆钢支撑,基于Revit平台开发了快速建模功能模块。首先,梳理了Revit软件平台二次开发的基本方式,确定了模块开发所用技术,提出了摇摆钢支撑快速建模功能模块开发的整体架构。随后,利用C#语言作为程序开发基础语言,针对新型摇摆钢支撑的各个部件,分别开发了相应的子模块,并介绍了各自的功能和实现路径,集成了摇摆钢支撑快速建模功能模块。最后,以某小学教学楼抗震加固项目为例,实现了新型摇摆钢支撑的BIM快速建模,从而在既有建筑模型的基础上形成了三维可视、信息共享的建筑模型,为新型摇摆结构加固既有建筑的BIM建模提供了新的方法。研究结果提升了摇摆钢支撑在BIM软件中的建模效率,拓展了BIM在土木工程新技术上的应用。