Interleukin-33 stimulates formation of functional osteoclasts from human CD14+ monocytes

Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14⁺ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)⁺ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14⁺ monocytes.     

Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

基于管道配置的电液位置控制系统同步特性研究

针对径锻机一级先导缸电液位置控制系统同步精度低的问题,运用AMESim软件研究了第一类管道配置对径锻机一级先导缸电液位置控制系统同步特性的影响。研究发现:系统同步误差随着管道长度的增加而增大,且伴有波动现象,管道长度为3m时最大同步误差是管道长度为1m时的1.4倍;管道长度为1m时的最大同步误差为无管道时的1.1倍;管道材料的杨氏弹性模量越小,对应系统的同步误差越大。     

恶性肿瘤中IGFBP-rP1的抑癌基因作用机制及其可能的临床实用价值

胰岛素样生长因子结合蛋白相关蛋白1(IGFBP-rP1)是近年来恶性肿瘤的研究热点.本文主要综述IGFBP-rP1在恶性肿瘤中的抑癌基因作用机制及可能的临床实用价值.IGFBP-rP1在恶性肿瘤中的作用广泛涉及细胞的增殖、衰老、凋亡、分化、血管生成等多方面,研究指出IGFBP-rP1可缩短细胞增殖周期并影响非停泊性生长从而抑制增殖,降低致瘤能力;调节BRAF-MEKERK信号通路及pRB、HSP60等相关蛋白的表达从而影响衰老及凋亡;主要通过IGF依赖方式抑制血管生成;而且IGFBP-rP1表达下降跟肿瘤细胞分化程度降低有关.研究显示IGFBP-rP1有一定的临床实用价值,如其表达量跟恶性肿瘤的进展相关,低表达提示某些化疗药物抵抗,可提示预后.而在恶性肿瘤中特异性地上调IGFBP-rP1,可抑制肿瘤增殖及血管生成、诱导细胞衰老凋亡、提高肿瘤分化程度及化疗敏感性,具有治疗意义,但研究者们还在努力探究,争取早日找到一种临床有效的靶向IGFBP-rP1的基因治疗方法.     

基于结构层贡献率的沥青路面抗车辙措施

采用环道试验及德国汉堡车辙试验方法,研究在中面层使用改性沥青对路面结构和组合结构抗车辙性能的影响,包括对结构层贡献率和对沥青层剪切流动变形的影响;探讨在中面层添加纤维对路面结构抗车辙能力的影响.研究结果表明:中面层使用改性沥青,能提高路面结构的整体抗车辙性能;使剪切流动变形由95.2%下降至84.4%;中面层变形贡献率达到60%以上,应该重视提高中面层的抗车辙能力;对于中面层采用普通沥青的结构,在中面层添加纤维可明显减少整个结构车辙深度,但对于中面层已采用改性沥青的结构,添加纤维减少车辙的效果不明显.     

试论高校思想政治教育模式的构建与创新

进入新时期以后，发展对高校的思想政治教育提出了新的要求。我国高校思想政治教育发展的实践表明，创新高校思想政治教育模式势在必行。只有勇于、善于创新，增强实效性、可持续性，形成全面育人的工作局面，构建多层次、多渠道的全方位育人工程，才能全面提升大学生素质。     

试论高职院校图书馆采编业务外包存在的问题及对策

文章阐述了高职院校图书馆采编业务外包存在数据质量问题、图书质量和配送时间问题、验收、数据查重以及加工场地问题等.提出了做好图书采购招标工作,认真选筛承包商;采编人员要加强监管,把好图书质量关;加强采编人员工作责任感,积极与外包书商协调沟通等相应的解决问题的对策.     

宽板坯凝固前沿轻压下率模型的研究

结合连铸坯凝固规律及轻压下技术改善铸坯中心偏析的冶金原理,建立宽板坯轻压下率理论模型。根据某厂连铸宽板坯实际生产条件,以传热模型计算的铸坯凝固温度数据作为轻压下率模型计算条件,分析拉速、浇注温度、坯壳凝固收缩特性对铸坯轻压下率的影响规律。结果表明,在相同的拉速和浇注温度条件下,铸坯轻压下率沿拉坯方向的分布总体呈减小趋势;拉速较高时的起始轻压下率小于拉速较低时对应的起始轻压下率;拉速与平均轻压下率呈线性递减关系:拉速每升高0.1m/min,平均轻压下率减小0.015mm/m;浇注温度越低,轻压下区起始轻压下率的值越高;浇注温度对平均轻压下率的影响较小,浇注温度每升高10℃,平均轻压下率仅减小0.002 5mm/m;铸坯外部凝固坯壳的收缩对整个轻压下区平均轻压下率的贡献量为20.4%～22.3%。     

深化我国住房保障制度改革 切实解决住房突出问题

住房制度改革以来,中国城市居民的居住条件在一定程度上有所改善,但完善的住房保障制度仍然没有建立起来,广大居民的住房需求仍未得到满足。因此,改善居民的居住水平,完善我国的住房保障制度,仍然是我们所要面临的主要任务。文章首先分析了我国现阶段住房保障制度中的存在问题,然后针对已出现的问题并结合我国国情,提出完善我国住房保障制度的相应对策。