Adipocyte differentiation induced using nonspecific siRNA controls in cultured human mesenchymal stem cells

RNA interference (RNAi) is gene silencing induced by double-stranded RNA of 21-23 nucleotides in length, termed small interfering RNA, or siRNA. RNAi-based techniques have been widely applied to elucidate gene function, identify drug targets, and used in trials as a promising adjunct to silence disease-causing genes. However, emerging evidence suggests unexpected changes in expression of untargeted genes as a consequence of an off-target effect by RNAi in mammalian cells. To date, our understanding of such effects on stem cells is limited. We transfected human fetal femur-derived mesenchymal stem cells using commercially available nonspecific siRNA controls and examined adipocyte differentiation in the cells using morphology, histochemistry, and quantitative real-time PCR to examine the expression of key genes for adipogenic or osteogenic differentiation. We report here the induction of adipocyte differentiation in human mesenchymal stem cells using nonspecific siRNAs raising concerns as to the specificity of RNAi in stem cells and, critically, a need to understand and delineate the rules governing the specificity of RNAi.     

黏附分子在肿瘤发生及发展中的作用

细胞黏附分子是以配体和受体相结合的形式,介导细胞与细胞间或细胞与基质间相互作用的一类分子,参与机体的多种重要生理和病理过程.近年来,在对肿瘤发生和发展的研究中发现,黏附分子可通过多种途径影响肿瘤的生长、浸润及转移过程.因此.对黏附分子在肿瘤发生和发展中作用及机制的深入研究,可为肿瘤早期诊断提供重要的分子指标和发现新的治疗靶标.并为进而形成临床诊疗新策略提供重要理论支持.现就几种重要黏附分子在肿瘤生长与转移中的作用进行综述.     

Analysis and comparison of the bacterial community in fermented grains during the fermentation for two different styles of Chinese liquor

Bacterial populations in fermented grains during fermentation may play important roles in Chinese liquor flavor. PCR-based denaturing gradient gel electrophoresis (DGGE) and 16S rRNA gene library analysis were performed to analyze the bacterial community structure of two styles of liquor. The results of DGGE profiles showed that bacterial diversity decreased with the fermentation process and Lactobacillus acetotolerans became the predominant species at the end of the fermentation. But the obvious differences of bacterial community appeared in the middle stage of two styles of liquor fermentation, in which the different upstream production techniques were used. Moreover, 16S rRNA gene libraries of two styles were constructed. A total of 125 and 107 clones, chosen from two libraries, were grouped into 46 and 49 operational taxonomic units (OTUs) by amplified ribosomal DNA restriction analysis. According to sequencing results of clones, the predominant bacteria in strong aroma style fermented grains were those from the class Bacilli, Bacteroidetes, and Clostridia, whereas the predominant bacteria in fermented grains of roasted sesame aroma style belonged to Bacilli, Flavobacteria, and Gammaproteobacteria. Molecular analysis of the bacterial diversity of the liquor fermentation will benefit the analysis of important microorganisms playing key roles in the formation of liquor flavor components.     

Properties of mutants of Synechocystis sp. strain PCC 6803 lacking inorganic carbon sequestration systems

A mutant (Delta5) of Synechocystis sp. strain PCC 6803 constructed by inactivating five inorganic carbon sequestration systems did not take up CO(2) or HCO(3)(-) and was unable to grow in air with or without glucose. The Delta4 mutant in which BicA is the only active inorganic carbon sequestration system showed low activity of HCO(3)(-) uptake and grew under these conditions but more slowly than the wild-type strain. The Delta5 mutant required 1.7% CO(2) to attain half the maximal growth rate. Electron transport activity of the mutants was strongly inhibited under high light intensities, with the Delta5 mutant more susceptible to high light than the Delta4 mutant. The results implicated the significance of carbon sequestration in dissipating excess light energy.     

HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells

Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Galphai-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.     

病理性疼痛的分子机制

持续性或慢性疼痛是很多患者的主要描述症状。然而,现在的治疗手段还不能充分解决某些疼痛或会引起不能忍受的副作用。近来疼痛生物学者阐明了大量的参与疼痛发生和维持的细胞和分子活动。如何更好的理解这些分子活动的机制将有助于发展高效的,特异性的治疗手段。背根神经节中小细胞神经元向脊髓传递温觉和伤害性信息的感觉传递。这些神经元的外周突感受生理性和化学性刺激后,可以在脊髓背角的中枢突通过突触囊泡和大致密性囊泡释放兴奋性的神经递质和神经肽。这种兴奋性突触传递可以被一些抑制因子调控如脊髓中间神经元和下行系统中分泌的阿片肽、GABA、甘氨酸、5-羟色胺。本文将回顾脊髓抑制性系统所取得的一些研究进展,将重点介绍在阿片受体转运,阿片镇痛以及吗啡耐晋研究中的进展,这些发现可能的治疗前景也会一并讨论。     

Habitat use of urban Tree Sparrows in the process of urbanization: Beijing as a case study

The Tree Sparrow (Passer montanus) is a dominant species in urban bird communities. With the development of urbanization, the habitats and sources of food for Tree Sparrows are decreasing. Can the urban Tree Sparrow adapt to changes in the urban environment? To answer this question, we studied the habitat use of Tree Sparrows in eight types of urban areas in Beijing. The results show that the number of both breeding and wintering Tree Sparrows decreased with increasing urbanization. The habitat use of Tree Sparrows, analyzed using stepwise discriminant analysis, was positively correlated with the number of brick bungalows, coniferous and broad-leaved trees and air conditioners. It was negatively correlated with the area of high buildings and hardened roads, pedestrian and automobile flux. This indicates that the Tree Sparrow had not adapted to rapid urbanization even though it is a generally adaptable species. Urban planning should take birds such as the Tree Sparrow into consideration. __________ Translated from Biodiversity Science, 2006, 14(5): 372–381 [译自:生物多样性]     

Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes

Background  

Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains.     

Crystal structure of Sulfolobus acidocaldarius aspartate carbamoyltransferase in complex with its allosteric activator CTP

Aspartate carbamoyltransferase (ATCase) is a paradigm for allosteric regulation of enzyme activity. B-class ATCases display very similar homotropic allosteric behaviour, but differ extensively in their heterotropic patterns. The ATCase from the thermoacidophilic archaeon Sulfolobus acidocaldarius, for example, is strongly activated by its metabolic pathway′s end product CTP, in contrast with Escherichia coli ATCase which is inhibited by CTP. To investigate the structural basis of this property, we have solved the crystal structure of the S. acidocaldarius enzyme in complex with CTP. Structure comparison reveals that effector binding does not induce similar large-scale conformational changes as observed for the E. coli ATCase. However, shifts in sedimentation coefficients upon binding of the bi-substrate analogue PALA show the existence of structurally distinct allosteric states. This suggests that the so-called “Nucleotide-Perturbation model” for explaining heterotropic allosteric behaviour, which is based on global conformational strain, is not a general mechanism of B-class ATCases.