在实验动物水平通过恢复和改善胰岛β细胞功能的糖尿病治疗新进展

糖尿病是一个世界性问题,在中国就有超过1.3亿人患有糖尿病.糖尿病主要分为1型糖尿病和2型糖尿病.遗憾的是,糖尿病至今尚未达成有效的预防和治愈手段.但是,近年来的一系列突破性的研究成果,让我们看到了治愈糖尿病的希望.在这里我们回顾了目前关于1型糖尿病和2型糖尿病可能的治愈途径的研究进展.这些途径包括胰岛移植和1型糖尿病...     

基于MaxEnt模型预测气候变化下杉木在中国的潜在地理分布

为研究杉木在中国的分布特征及其对气候变化的响应模式,本研究基于现有分布记录,应用最大熵(MaxEnt)模型和地理信息系统方法,结合气候、地形等环境要素,预测杉木在当前和未来气候变化下的潜在适生区。结果表明: 影响杉木分布的最主要因素是年平均降水量,在当前气候下,杉木适生区合计面积328万km²,占全国陆地总面积的34.5%,低、中和高适生区分别占18.3%、29.7%与52.0%。在未来气候情景下,杉木生长的适宜性在我国总体上呈上升趋势,适生区面积随气候变化增大,且明显向北扩张,南方湿润亚热带地区形成集中连片高适生区。模型经受试者工作特征曲线检验,训练集平均受试者工作特征曲线下面积为0.91,可信度高。     

Signal transduction initiated by extracellular nucleotides regulates the high affinity ligand recognition of the adhesive receptor CD11b/CD18

A variety of monocyte/neutrophil adhesive functions is coordinated by the CD11b/CD18 complex, a leukocyte-restricted member of integrin receptors. Previous studies have shown that the adenine nucleotide ADP produces a transient and high affinity recognition state of CD11b/CD18 for its complementary ligands fibrinogen and factor X. We have now characterized the process of intracellular signalling initiated in monocytes by ADP. Further, we have causally related these events to the qualitative upregulation of CD11b/CD18, as exemplified by its inducible binding of factor X. Micromolar concentrations of ADP or ATP produce dose-dependent increase in monocyte cytosolic free [Ca2+]i through mobilization from intracellular stores coupled with a sustained, EGTA-sensitive, influx of Ca2+ from the external compartment. This Ca2+ response was kinetically and quantitatively heterogeneous when analyzed at the single cell level. Ca2+ channel antagonists nifedipine or verapamil blocked the sustained phase of ADP-induced Ca2+ entry and inhibited 125I-factor X binding to CD11b/CD18 in a dose-dependent manner. Nifedipine-sensitive Ca2+ channels are gated by variations in transmembrane potential in a variety of cells. In monocytes, depolarizing conditions by high external [K+] or by the Na+ ionophore gramicidin D mimicked the stimulatory effect of ADP, inducing increased cytosolic free [Ca2+]i and 125I-factor X binding to CD11b/CD18. In contrast, these responses were both abrogated by hyperpolarization with the K+ ionophore valinomycin. These data suggest that a sustained increase in monocyte cytosolic free [Ca2+]i coupled with variations in transmembrane potential regulate the high affinity receptor function of CD11b/CD18. Although prototypically exemplified for monocyte stimulation with adenine nucleotides, this pathway of intracellular signalling might provide a general mechanism for transient and qualitative functional upregulation of integrin receptors.     

Immunochemical heterogeneity of human plasma high density lipoproteins. Identification with apolipoprotein A-I- and A-II-specific monoclonal antibodies

Three mouse monoclonal antibodies specific for human apolipoprotein (apo) A-I and one specific for human apo-A-II were characterized with respect to their binding of high density lipoprotein (HDL) particles in solution. The apo-A-II-specific antibody bound 85% of 125I-HDL and 100% of soluble 125I-apo-A-II. However, none of the apo-A-I-specific antibodies bound greater than 60% of either HDL or soluble apo-A-I. Technical issues such as limiting amounts of antibody or antigen, radioiodination of the ligands, unavailability of the epitopes for reaction with antibody, selective binding of apo-A-I isoforms, and individual allotypic differences in apo-A-I were not responsible for the observed incomplete binding of all HDL and apo-A-I. The results suggested the existence of intrinsic immunochemical heterogeneity of apo-A-I both as organized on HDL as well as in free apo-A-I in solution. The validity of this observed heterogeneity was supported by demonstrating that (i) increased binding of HDL occurred when each of the apo-A-I antibodies was combined to form an oligoclonal antibody mixture, and (ii) 100% binding of HDL occurred when two apo-A-I antibodies were combined with the single apo-A-II antibody. To understand the basis for the heterogeneity of expression of apo-A-I epitopes on HDL, two hypotheses were examined. The first hypothesis that these apo-A-I antibodies distinguished apo-A-I molecules from different synthetic sources was not substantiated. Two of the antibodies bound epitopes on apo-A-I molecules in both thoracic duct lymph as an enriched source of intestinal HDL and the culture supernatants of the hepatic cell line Hep G2 as a source of hepatic HDL. The second hypothesis that the antibodies identified differences in the expression of apo-A-I on HDL subpopulations that were distinguished on the basis of size or net particle charge, i.e. organizational heterogeneity, appeared to provide the best available explanation for the immunochemical heterogeneity of apo-A-I in HDL. Relative differences in the expression of three distinct apo-A-I epitopes were demonstrated in HDL subpopulations obtained by either density gradient ultracentrifugation or chromatofocusing. In light of these studies, we conclude that there is intrinsic heterogeneity in the expression of intramolecular loci representing the apo-A-I epitopes identified by our monoclonal antibodies. Such heterogeneity must be considered in analysis of the biology and physiology of apo-A-I and lipoprotein particles bearing this chain.