体细胞直接转化为多能干细胞的新方法

胚胎干细胞具有自我复制、高度增殖、多向分化潜能、可植入性和重建能力等特征.对于诸如青少年糖尿病、帕金森综合症和心脏病等需要通过细胞移植来治疗的疾病而言,从人的囊胚内细胞团获得胚胎干细胞系是最理想的供体来源.然而,目前实验和医疗还要考虑到利用人类胚胎的一些伦理问题和组织排异反应.避免这些问题的可能途径就是通过已分化体细胞的重新编程来直接转化为诱导性多能干细胞,它们具有类似ES细胞的功能.目前,获得诱导性多能干细胞的设想已初步实现了从老鼠到人的突破.以下主要对体细胞直接转化为诱导性多能干细胞的研究现状、方法和转录因子在诱导体细胞重新编程中发挥的作用等内容进行了概述,以期为干细胞研究者进行更深入的研究提供一定的借鉴.     

Synthesis and characterization of 5,6,7,8-tetrahydroquinoline C5a receptor antagonists

A novel series of substituted 2-aryl-5-amino-5,6,7,8-tetrahydroquinoline C5a receptor antagonists is reported. Synthetic routes were developed that allow the substituents on the tetrahydroquinoline core to be efficiently varied, facilitating determination of structure-activity relationships. Members of the series display high binding affinity for the C5a receptor and are potent functional antagonists.     

Functional analysis of protein disulfide isomerases in blood feeding, viability and oocyte development in Haemaphysalis longicornis ticks

Three protein disulfide isomerases from Haemaphysalis longicornis ticks (designated as HlPDI-1, HlPDI-2, and HlPDI-3) were previously identified. In order to further analyze their biological functions, the dsRNA of each HlPDI gene and one dsRNA combination of HlPDI-1/HlPDI-3 were separately injected into female ticks. Reduction of gene and protein expression of HlPDIs by RNA interference (RNAi) was demonstrated by real-time PCR, RT-PCR and Western blot analysis. In single dsRNA-injected groups, HlPDI-1 RNAi impacted tick blood feeding and oviposition, HlPDI-2 RNAi impacted tick viability and HlPDI-3 RNAi had no significant impact by itself. However, the injection of a combination of HlPDI-1/HlPDI-3 dsRNA had synergistic effects on tick viability. Furthermore, the midgut and cuticle were severely damaged in HlPDI-2 dsRNA-injected ticks and HlPDI-1/HlPDI-3 dsRNA-injected ticks, respectively, and disruption of HlPDI genes led to a significant reduction of disulfide bond-containing vitellogenin (Vg) expression in ticks. These results indicate that PDIs from H. longicornis are involved in blood feeding, viability and oocyte development, probably by mediating the formation of disulfide bond-containing proteins of the ticks and the formation of basement membrane and cuticle components such as extracellular matrix (ECM). This is the first report on the functional analysis of PDI family molecules as well as the interactions of PDI and other molecules in blood-feeding arthropods.     

FMRP acts as a key messenger for dopamine modulation in the forebrain

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that controls translational efficiency and regulates synaptic plasticity. Here, we report that FMRP is involved in dopamine (DA) modulation of synaptic potentiation. AMPA glutamate receptor subtype 1 (GluR1) surface expression and phosphorylation in response to D1 receptor stimulation were reduced in cultured Fmr1(-/-) prefrontal cortex (PFC) neurons. Furthermore, D1 receptor signaling was impaired, accompanied by D1 receptor hyperphosphorylation at serine sites and subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in both PFC and striatum of Fmr1(-/-) mice. FMRP interacted with GRK2, and pharmacological inhibition of GRK2 rescued D1 receptor signaling in Fmr1(-/-) neurons. Finally, D1 receptor agonist partially rescued hyperactivity and enhanced the motor function of Fmr1(-/-) mice. Our study has identified FMRP as a key messenger for DA modulation in the forebrain and may provide insights into the cellular and molecular mechanisms underlying fragile X syndrome.     

Microscale HPLC enables a new paradigm for commercialization of complex chiral stationary phases

The small column size (0.3 mm i.d. x 15 cm) used in microscale HPLC contains only a small fraction (<1%) of the chromatographic packing material of a typical analytical HPLC column. Consequently, chromatographic stationary phases that are prohibitively expensive in conventional HPLC, owing either to synthetic complexity or costly starting materials, may become commercially viable in the microscale format. To illustrate this point, a previously described, synthetically complex, crown ether chiral stationary phase was prepared and evaluated in the microscale format, showing excellent separation of the enantiomers of underivatized amine analytes.     

<Emphasis Type="Italic">Saprolegnia brachydanis</Emphasis>, A New Oomycete Isolated from Zebra Fish

Saprolegnia brachydanis is described from zebra fish (Brachydanio rerio) in Wuhan, Hubei Province, China. The species is illustrated and compared with other species of the genus. The distinctive characteristics of S. brachydanis are the production of glomerulate oogonia wrapped around by predominantly monoclinous antheridia which can be up to eight in one oogonium. The oogonial stalks are short, straight, or curved and the antheridia, twisted, can enwind one or more oogonia. The oospores cannot mature or easily abort. Morphological features of the oomycete and the ITS sequence of its rDNA as well as the comparison with related species are discussed in this article.     

Identification and Experimental Verification of Protective Antigens Against <Emphasis Type="Italic">Streptococcus suis</Emphasis> Serotype 2 Based on Genome Sequence Analysis

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that can cause severe disease and even death in both humans and swine. No effective vaccine is clinically available. In this study, a reverse vaccinology method was first applied to identify protective antigens against S. suis 2. As a consequence, 153 genes encoding vaccine candidates were selected from the whole genome sequence by means of bioinformatics analysis, from which 10 genes were selected based on experimental evidences arising from the study of related bacteria such as Streptococcus pneumoniae, group B streptococcus, S. suis and so on. Of 10 target genes, 8 were successfully expressed in Escherichia coli Rosetta, and expressed proteins were purified and used as the immunogens for evaluating vaccine efficacy in a mouse infection model. The results have confirmed that RTX family exoprotein A (RfeA), epidermal surface antigen (ESA), immunoglobulin G (IgG)-binding protein (IBP), and suilysin (SLY) can induce a protective response of the vaccinated animals against S. suis 2, whereas RfeA, ESA, and IBP mainly induce humoral-mediated immunity, and SLY elicits a combined pattern of both humoral- and cellular-mediated immunity. Although immunoprotection of SLY against S. suis 2 was reported previously, RfeA, ESA, and IBP were explored first in this study.     

A new strategy to apply Bacillus subtilis MA139 for the production of solid-state fermentation feed

Aim:  The study investigated the potential of using Bacillus subtilis MA139 in combination with Lactobacillus fermentum and Saccharomyces cerevisae to produce solid-state fermentation feed.
Methods and Results:  In a pure fermentation, B. subtilis MA139 was able to grow and synthesize antimicrobial substances at temperatures from 25 to 37°C and at a pH from 5·0 to 9·0. Subsequently, B. subtilis MA139, Lact. fermentum and S. cerevisae were used as starter strains co-inoculated in unsterilized substrate (feed-grade soybean meal and wheat bran). Following 10 days of fermentation in a newly developed plastic bag equipped with a one-way valve, lactic acid bacteria and Bacillus became the predominant strains while S. cerevisae cells decreased slightly. Enterobacteriaceae ( Escherichia coli K88 and Salmonella typhimurium ) were not detected.
Conclusions:  Use of B. subtilis MA139 as a starter strain co-inoculated with S. cerevisae and Lact. fermentum successfully controlled the growth of enterobacteriaceae.
Significance and Impact of the Study:  This study provided a facile and low-cost way to produce solid-state fermentation feed.