A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions

Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease.     

An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo

The application of RNA interference (RNAi) to mammalian systems has the potential to revolutionize genetics and produce novel therapies. Here we investigate whether RNAi applied to a well-characterized gene can stably suppress gene expression in hematopoietic stem cells and produce detectable phenotypes in mice. Deletion of the Trp53 tumor suppressor gene greatly accelerates Myc-induced lymphomagenesis, resulting in highly disseminated disease. To determine whether RNAi suppression of Trp53 could produce a similar phenotype, we introduced several Trp53 short hairpin RNAs (shRNAs) into hematopoietic stem cells derived from E(mu)-Myc transgenic mice, and monitored tumor onset and overall pathology in lethally irradiated recipients. Different Trp53 shRNAs produced distinct phenotypes in vivo, ranging from benign lymphoid hyperplasias to highly disseminated lymphomas that paralleled Trp53-/- lymphomagenesis in the E(mu)-Myc mouse. In all cases, the severity and type of disease correlated with the extent to which specific shRNAs inhibited p53 activity. Therefore, RNAi can stably suppress gene expression in stem cells and reconstituted organs derived from those cells. In addition, intrinsic differences between individual shRNA expression vectors targeting the same gene can be used to create an 'epi-allelic series' for dissecting gene function in vivo.     

半空心铆钉自冲铆接的工艺参数及铆接质量的判定

自冲铆接是在板料和铆钉之间形成连接而不需要预冲孔的新工艺，探讨了检测自冲铆接质量的直接试验法和观测法，并在原有观测法的基础上提出了补充意见．开展了模具设计、铆钉尺寸选择及二者与板料匹配等方面的研究，提出了模具设计的依据和方法．同时进行了自冲铆接效果的试验研究，结合自冲铆接试验结果，分析了模具、铆钉以及板料的材质性能等卤素对铆接质量的影响．研究和试验分析表明，自行设计的半空心铆钉和模具可以获得良好的铆接质量，可作为模具设计的参考和依据．     

Status and life history notes on the native fishes of the Alvord Basin, Oregon and Nevada

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WTI crude oil option implied VaR and CVaR: An empirical application

Using option market data we derive naturally forward‐looking, nonparametric and model‐free risk estimates, three desired characteristics hardly obtainable using historical returns. The option‐implied measures are only based on the first derivative of the option price with respect to the strike price, bypassing the difficult task of estimating the tail of the return distribution. We estimate and backtest the 1%, 2.5%, and 5% WTI crude oil futures option‐implied value at risk and conditional value at risk for the turbulent years 2011–2016 and for both tails of the distribution. Compared with risk estimations based on the filtered historical simulation methodology, our results show that the option‐implied risk metrics are valid alternatives to the statistically based historical models.     

Comparison of vegetation patterns resulting from bulldozing and two-way chaining on a Utah pinyon-juniper big game range

Two adjacent mechanically treated pinyon-juniper ( Pinus spp. and Juniperus spp.) big game winter range sites in central Utah were sampled in 1981 to estimate vegetational differences and tree mortality from the two treatments. One site was treated by selectively bulldozing in 1957 and the other was double chained in 1965. Both treatments significantly reduced tree and litter cover, whereas significant increases were found for native grasses and shrubs compared to a nearby untreated site. Juniper cover for the untreated site was 35.5% compared to only 1.4% for the bulldozed area and 4.1% for the two-way chained area. Browse species densities were increased by the mechanical treatments. The use of different mechanical treatments on separate smaller portions of critical areas of big game winter range would help provide: (1) for both long-term and short-term use of a critical wintering area, (2) greater overall productivity and carrying capacity, and (3) greater diversity by creating more edge effect between the differently treated and untreated areas.