CD8<Superscript>+</Superscript> Tregs in autoimmunity: learning “self”-control from experience

Autoreactive CD8⁺ regulatory T cells (Tregs) play important roles as modulators of immune responses against self, and numerical and functional defects in CD8⁺ Tregs have been linked to autoimmunity. Several subsets of CD8⁺ Tregs have been described. However, the origin of these T cells and how they participate in the natural progression of autoimmunity remain poorly defined. We discuss several lines of evidence suggesting that the autoimmune process itself promotes the development of autoregulatory CD8⁺ T cells. We posit that chronic autoantigenic exposure fosters the differentiation of non-pathogenic autoreactive CD8⁺ T cells into antigen-experienced, memory-like autoregulatory T cells, to generate a “negative feedback” regulatory loop capable of countering pathogenic autoreactive effectors. This hypothesis predicts that approaches capable of boosting autoregulatory T cell memory will be able to blunt autoimmunity without compromising systemic immunity.     

The histidine triad nucleotide-binding protein 1 supports mu-opioid receptor–glutamate NMDA receptor cross-regulation

A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR. These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein 1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism. Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength. Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms independent of NMDAR.     

The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor

The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are up-regulated in various tumors. We show that CXCR4-transfected cells migrate toward SDF1 on collagen (CG) and do not on vitronectin (VN). Co-expression of cell-surface uPAR, which is a VN receptor, impairs SDF1-induced migration on CG and allows migration on VN. Blocking fMLP receptors (fMLP-R), alpha-v integrins or the uPAR region capable to interact with fMLP-Rs, impairs migration of uPAR/CXCR4-transfected cells on VN and restores their migration on CG. uPAR co-expression also reduces the adherence of CXCR4-expressing cells to various components of the extracellular matrix (ECM) and influences the partitioning of beta1 and alpha-v integrins to membrane lipid-rafts, affecting ECM-dependent signaling. uPAR interference in CXCR4 activity has been confirmed in cells from prostate carcinoma. Our results demonstrate that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins.     

Highly reactive oxygen species: detection, formation, and possible functions

The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies.     

Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules

Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study reveals an additional level of plasticity modulating the resolution of inflammation.     

聚合氯化铝组合芽孢杆菌发酵液法对链状裸甲藻孢囊种源萌发调控研究

对比不同浓度梯度的聚合氯化铝(poly aluminium chloride,以下简称"PAC")和不同发酵时间、不同投加量的Ba3芽孢杆菌(Bacillus)发酵液及两者组合法对链状裸甲藻(Gymnodinium catenatum)的除藻效果,用最佳投加量进行了沉积物种源萌发调控实验,探究了PAC组合菌发酵液方法对...     

浅谈新疆某泥石流成因及防治措施

泥石流是常见的地质灾害的一种,严重影响周边居民的生命财产安全。该文从泥石流影响区的工程地质环境调查人手,以泥石流发育特征作为理论出发点,分析影响泥石流发生的各种因素,探讨泥石流形成过程,找出影响泥石流的主控因素,并且从各个方面分析泥石流的成因,最后研究出泥石流形成演化机理,并得出相应的结论以及对泥石流的防治建议。     

高频GPS观测发现可靠的大地震前兆信号?

<正>地震是地球上重要且频发的一种突发事件,并引发多种高危险链生灾害,给人类社会带来巨大损失.目前,对地震预报有两种截然不同的观点:一种是以Geller等人^[1]为代表,认为地震不可预报.地震过程是非线性自组织系统,混沌理论框架下,可以对地震群体进行统计描述,而单个地震事件不能预报;与之相对,另一种观点则认为地震作为一种自然现象可被认知,地震预报本质上可行.     

平屋顶水平封闭方腔空气层厚度数值分析

为分析平屋顶水平封闭方腔作为保温系统时其内部空气层的相对最佳厚度,通过建立二维数值模型,选择"Presto!"压力插值格式及SIMPLE(Semi-Implicit Method for Pressure-Linked Equations)解耦算法,计算了在不同边界温差和边界材料导热系数下平屋顶水平封闭方腔内辐射传热量和对流换热量及其随空气层厚度的变化.在一定条件下,通过对计算结果进行回归分析,得到平屋顶水平封闭方腔在不同温差和不同边界材料导热系数下的相对最佳空气层厚度值.