Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer

Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a dozen species of mammals have been cloned using this technology. One hypothesis for the limited success of cloning via SCNT (1%-5%) is that the clones are likely to be derived from adult stem cells. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.     

IFT54 regulates IFT20 stability but is not essential for tubulin transport during ciliogenesis

Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT-B complex and is also associated with cytoplasmic microtubules (MTs). Loss of IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled-coil (CC) domain binds IFT20. However, the precise function of these domains in vivo is not well understood. We showed that in Chlamydomonas, loss of IFT54 completely blocks ciliogenesis but does not affect spindle formation and proper cell cycle progression, even though IFT54 interacts with mitotic MTs. Interestingly, IFT54 lacking the CH domain allows proper flagellar assembly. The CH domain is required for the association of IFT54 with the axoneme but not with mitotic MTs, and also regulates the flagellar import of IFT54 but not IFT81 and IFT46. The C-terminal CC domain is essential for IFT54 to bind IFT20, and for its recruitment to the basal body and incorporation into IFT complexes. Complete loss of IFT54 or the CC domain destabilizes IFT20. ift54 mutant cells expressing the CC domain alone rescue the stability of IFT20 and form stunted flagella with accumulation of both IFT-A component IFT43 and IFT-B component IFT46, indicating that IFT54 also functions in IFT turn-around at the flagellar tip.     

探月工程三期月地高速再入返回飞行器防热系统设计与验证

本文针对月地高速再入返回的高焓、二次大气层再入、高热流密度峰值与长加热时间耦合的气动加热环境特点,提出了飞行器防热系统设计方案,研制了七种新型碳硅复合烧蚀防热材料,建立了防热系统分析模型,并完成了地面试验验证.经对飞行试验数据的详细分析,结果表明防热系统的实际性能与设计预期一致.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

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.     

Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)

The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.     

试论图书馆联盟在信息网格应用中的作用

介绍了信息网格和图书馆联盟的涵义,阐述了网格技术应用过程中的问题,探讨了图书馆联盟在信息网格应用中的作用,指出图书馆联盟作为图书馆际合作组织,在信息网格时代应利用信息网格技术推动图书馆际间资源共享,提高图书馆信息服务质量和能力,促进信息网格的信息连通,使其逐渐成熟。     

Approximate Controllability for Degenerate Heat Equation with Bilinear Control

This paper investigates the nonnegative approximate controllability for the one-dimensional degenerate heat equation governed by bilinear control. Both non-controllability and approximate controllability are studied for the system. If the control is restricted to act on a fixed domain, it is not controllable. If the control is allowed to mobile, it is approximately controllable.     

水栖性的棘胸蛙身体大小不随环境水热梯度及净初级生产力梯度而分化

之前的研究发现不同地理种群棘胸蛙(Quasipaa spinosa)的身体大小随着环境生产力以及年最低温的降低而增大,因为更大的身体利于在生产力水平较低的环境中耐受饥饿并利于在寒冷的环境条件下保存热量.然而在种间水平上进行的相关研究发现:由于大部分时间生活在水体这种相对稳定的环境中,水栖性无尾类的身体大小并不受宏观水热波动的影响.为了更好地探究这个问题,我们以棘胸蛙为研究对象,在之前的基础上选择更多的研究地点及更多的环境因子,研究其身体大小的地理分化格局并探究潜在机制.与之前的发现不同,作为一种水栖性无尾类,棘胸蛙的身体大小并不受环境水热梯度以及净初级生产力梯度的影响.导致这种现象的原因可能是水栖性的生境偏好缓和了棘胸蛙受到的来自宏观环境水热波动的影响,所以它们并不通过改变身体大小来适应宏观环境梯度.此外由于棘胸蛙的肉食性,环境初级生产力并不能有效地衡量其食物供给,其身体大小是否受到食物供给量的影响仍有待深入探究.     

论桥梁抗震模型建立分析的目的

文章论述了桥梁抗震评估的建立模型和分析手段,其目的是用结构位移、构件受力及变形对桥梁地震反应进行定量化分析。