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991.
随着细胞与组织工程的迅猛发展,能够促进细胞黏附、生长和分化的生物材料基质支架的研究日益重要。具有生物相容性且含水量超过99%的自组装肽水凝胶因其很好地符合理想的生物材料基质支架标准而备受重视。这类自我互补的两亲寡肽含50%的带电残基,并且以交替的离子亲水性和不带电的氨基酸残基周期性重复为特征;在其寡肽的氨基末端可用直接固相合成法修饰几个短序列生物活性模体进行功能化,用以促进不同细胞的黏附生长和靶向定位。现对自组装肽水凝胶的结构特征、自组装机制、对细胞黏附生长的影响以及未来自组装肽生物材料设计的目标进行综述. 相似文献
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994.
Protein function is mediated by different amino acid residues, both their positions and types, in a protein sequence. Some amino acids are responsible for the stability or overall shape of the protein, playing an indirect role in protein function. Others play a functionally important role as part of active or binding sites of the protein. For a given protein sequence, the residues and their degree of functional importance can be thought of as a signature representing the function of the protein. We have developed a combination of knowledge- and biophysics-based function prediction approaches to elucidate the relationships between the structural and the functional roles of individual residues and positions. Such a meta-functional signature (MFS), which is a collection of continuous values representing the functional significance of each residue in a protein, may be used to study proteins of known function in greater detail and to aid in experimental characterization of proteins of unknown function. We demonstrate the superior performance of MFS in predicting protein functional sites and also present four real-world examples to apply MFS in a wide range of settings to elucidate protein sequence-structure-function relationships. Our results indicate that the MFS approach, which can combine multiple sources of information and also give biological interpretation to each component, greatly facilitates the understanding and characterization of protein function. 相似文献
995.
Autophagy has recently been shown to be an important component of the innate immune response. The signaling pathways leading to activation of autophagy in innate immunity are not well studied. Our recent study shows that Toll-like receptor 4 (TLR 4) serves as an environmental sensor for autophagy. We define a new molecular pathway in which lipopolysaccharide (LPS) induces autophagy in human and murine macrophages by a pathway regulated through Toll-interleukin 1 receptor domain-containing adaptor-inducing interferon-beta (TRIF)-dependent, myeloid differentiation factor 88 (MyD88)-independent TLR4 signaling. Receptor-interacting protein (RIP1) and p38 mitogen-activated protein-kinase (MAPK) are downstream components of this pathway. This signaling pathway does not affect cell viability, indicating that it is distinct from an autophagic death signaling pathway. We further show that LPS-induced autophagy can enhance mycobacterial co-localization with the autophagosomes. The above study raises important questions. (1) What is the complete signaling pathway for LPS-induced autophagy? (2) Does TLR3 mediate autophagy? (3) What are the mechanisms that determine whether autophagy acts as a pro-death or pro-survival pathway? (4) What are the physiological functions of LPS-induced autophagosomes? Future studies examining the above questions should provide us with important clues as to how autophagy is regulated in innate immunity, and how autophagy can be utilized in pathogen clearance. 相似文献
996.
体细胞直接转化为多能干细胞的新方法 总被引:1,自引:0,他引:1
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. 相似文献
997.
Barbay JK Gong Y Buntinx M Li J Claes C Hornby PJ Van Lommen G Van Wauwe J He W 《Bioorganic & medicinal chemistry letters》2008,18(8):2544-2548
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. 相似文献
998.
Functional analysis of protein disulfide isomerases in blood feeding, viability and oocyte development in Haemaphysalis longicornis ticks 总被引:1,自引:0,他引:1
Liao M Boldbaatar D Gong H Huang P Umemiya R Harnnoi T Zhou J Tanaka T Suzuki H Xuan X Fujisaki K 《Insect biochemistry and molecular biology》2008,38(3):285-295
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. 相似文献
999.
Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases 总被引:1,自引:0,他引:1
1000.
Wang H Wu LJ Kim SS Lee FJ Gong B Toyoda H Ren M Shang YZ Xu H Liu F Zhao MG Zhuo M 《Neuron》2008,59(4):634-647
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. 相似文献