Regulation of B cell tolerance by the lupus susceptibility gene Ly108

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.     

Neonatal tolerance induced by antibody against antigen-specific receptor

Specific immunologic unresponsiveness is induced by injecting adult or neonatal mice with antibody against antigen-specific receptor (antireceptor antibody). Suppression in mice treated as adults lasts several weeks, and cells from these suppressed mice respond normally in culture. In contrast, unresponsiveness induced in neonatal mice is long-lasting; cells from these mice do not respond in culture and do not affect the response of normal cells. Evidently, antireceptor antibody reversibly blocks antigen receptors in adult animals, but induces unresponsiveness in neonatal mice by depleting the clone of receptor-bearing cells.     

Restoration of LDL receptor activity in mutant cells by intercellular junctional communication

Exchange of small molecules between cells through intercellular junctions is a widespread phenomenon implicated in many physiological and developmental processes. This type of intercellular communication can restore the activity of low-density lipoprotein (LDL) receptors in mammalian cells that are deficient in the enzyme UDP-Gal/UDP-GalNAc 4-epimerase. Pure cultures of the 4-epimerase mutant are unable to synthesize normal carbohydrate chains on LDL receptors and many other glycoproteins and therefore do not express LDL receptor activity. When these cells are cocultivated with cells expressing normal 4-epimerase activity, the structure and function of LDL receptors are restored to normal by the transfer of this enzyme's products through intercellular junctions. The formation of functional junctions does not require normal glycosylation of membrane proteins. Because many convenient assays and selections for LDL receptor activity are available, this mutant can provide a powerful new tool for biochemical and genetic studies of intercellular junctional communication.     

Prevention of murine lupus nephritis by carrier-dependent induction of immunologic tolerance to denatured DNA

Four nucleosides were covalently bound to isogeneic mouse immunoglobulin G (IgG) and injected into New Zealand mice. Mice that received the tetranucleoside isogeneic IgG from birth to 5 months of age failed to make antibody to denatured DNA. In contrast, mice that were similarly treated with tetranucleoside bovine serum albumin or tetranucleoside free of carrier produced the same amount of antibody to denatured DNA as did untreated mice of this strain. Mice that were rendered tolerant to denatured DNA by tetranucleoside isogeneic IgG failed to develop the chronic membranous glomerulonephritis that characterizes the renal lesions in animals of this strain.     

瘢痕疙瘩皮损中抑制型SMAD mRNA的低表达

用定量Real-time PCR(LightCycler)法分别检测了瘢痕疙瘩,正常瘢痕及正常皮肤组织中不同类型的SMADs(SMAD2、3、4、6、7)mRNA的表达水平.结果显示抑制型SMADs(SMAD6、SMAD7)的mRNA水平在瘢痕疙瘩的组织中明显低于正常瘢痕(P＜0.01,P＜0.05)及正常皮肤组织(P＜0.01,P＜0.001).然而,其它类型的SMADs(SMAD2、3、4)mRNA的表达在瘢痕疙瘩,正常瘢痕以及正常皮肤组织中均无明显差异(P＞0.05).表明瘢痕疙瘩的皮肤组织中存在有抑制型SMADs(SMAD6、SMAD7)的mRNA水平表达的下调,此结果提示缺乏抑制型SMAD的负反馈抑制在瘢痕疙瘩的发病中可能起着重要的作用.     

Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801.

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.     

Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor

The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG) was investigated in a murine model of immune thrombocytopenia. Administration of clinically protective doses of intact antibody or monomeric Fc fragments to wild-type or Fcgamma receptor-humanized mice prevented platelet consumption triggered by a pathogenic autoantibody. The inhibitory Fc receptor, FcgammaRIIB, was required for protection, because disruption either by genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of IVIG. Protection was associated with the ability of IVIG administration to induce surface expression of FcgammaRIIB on splenic macrophages. Modulation of inhibitory signaling is thus a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.     

微生物修复二氯喹啉酸污染农田的研究进展

二氯喹啉酸在土壤中残效期长,易给下茬作物造成药害。综述了二氯喹啉酸除草剂的应用概况、二氯喹啉酸污染农田的物理、化学和生物降解等修复措施以及微生物降解菌的筛选、鉴定和应用进展,讨论了利用微生物修复二氯喹啉酸污染土壤过程中存在的问题和困难,旨在为开展土壤微生物降解土壤中残留的二氯喹啉酸提供参考。     

雄激素受体及共调节因子在睾酮调节绵羊附睾GPX5表达中的作用分析

为探究雄激素受体(Androgen receptor,AR)及共调节因子对绵羊附睾上皮细胞(Epididymal epithelial cells,EECs)谷胱甘肽过氧化物酶5(Glutathione peroxidase 5,GPX5)的调节机制,本研究采用CCK-8检测睾酮对EECs增殖的影响;利用qRT-PCR、免疫荧光法和 Western Blot法分别检测AR、GPX5、甾体激素受体共激活子 1(Steroid receptor coactivator 1,SRC-1)、CREB结合蛋白(cAMP-response element-binding protein,CBP)、p300和核受体共抑制因子2(Nuclear receptor corepressor 2,NCOR2)的mRNA水平和蛋白表达情况,采用双荧光素酶报告基因测定干扰SRC-1或p300后EECs的荧光素酶活性。结果表明:1)与对照组相比,100 nmol/L睾酮组细胞中的GPX5 mRNA和蛋白表达量极显著升高(P<0.01),1 000 nmol/L睾酮组细胞中的GPX5 mRNA和蛋白表达量差异不显著(P>0.05),但分别极显著(P<0.01)和显著(P<0.05)低于100 nmol/L睾酮组;100 nmol/L睾酮组细胞中的AR mRNA和蛋白表达量分别呈极显著(P<0.01)和显著(P<0.05)高于对照组,然而1 000 nmol/L睾酮组细胞中的AR mRNA和蛋白的表达量显著低于对照组(P<0.05);1 000 nmol/L睾酮组细胞中的CBP、p300、SRC-1蛋白表达极显著高于对照组(P<0.01),特别是核内的表达量明显增高。2)与对照组相比,siRNA-AR组细胞中的GPX5 mRNA和蛋白的表达量差异不显著(P>0.05),而SRC-1和p300蛋白表达量极显著升高(P<0.01)。pcDNA3.1-AR组GPX5 mRNA和蛋白表达量较对照组呈极显著(P<0.01)和显著(P<0.05)升高。3)siRNA-SRC-1 和siRNA-p300组细胞中的GPX5 mRNA和蛋白表达量较对照组均显著降低(P<0.05),而AR的蛋白表达量与对照组差异不显著(P>0.05),AR的转录活性显著降低(P<0.05)。综上,睾酮对绵羊EECs GPX5、AR及其共调节因子的表达具有浓度依赖性的调节效应,睾酮通过AR及其共调节因子SRC-1和p300/CBP的协同调节GPX5表达。本研究为探究GPX5在绵羊附睾中的调节机制提供理论依据。     

Restoration of photographs by neutron activation

Badly faded or stained photographs or radiographs, negative or positive, can be restored by use of neutron activation and autoradiography, provided that at least a trace of image silver is present and that the picture is relatively free of halogens and other silver.     

差异表达研究方法及其在作物耐旱基因筛选中的应用

抑制性消减杂交（ssn）、cDNA微阵列技术,差异显示PCR（DD-PCR）、代表性差异分析（RDA）、表达序列标签（ESTs）、基因表达连续性分析（SAGE）、cDNA扩增片段长度多态性（cDNA-AFLP）几种技术是目前基因差异表达的主要研究方法。本文分析了各种方法的优缺点,综述了干旱胁迫下玉米、水稻、小麦基因差异表达的研究进展后认为,对干旱胁迫与正常浇水对照的基因差异表达研究,进而分离抗旱基因,是进行作物抗耐旱转基因、创造抗耐旱种质资源,进而选育抗耐旱作物新品种的基础,在基因差异表达研究中,以采用cDNA—AFLP技术为宜。     

Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice

Lineage-specific regulatory elements can be used to direct expression of a variety of genes to specific tissues in transgenic mice. If the hybrid constructs contain a gene encoding a cytotoxic gene product, then genetic ablation of a specific cell lineage can be achieved. We have generated six transgenic mice by introducing into fertilized eggs the mouse gamma 2-crystallin promoter fused to the coding region of the diphtheria toxin A-chain gene. Three of these mice and all the transgenic offspring analyzed were microphthalmic. The lenses of these mice displayed considerable heterogeneity: some were almost normal morphologically but reduced in size, whereas others were grossly aberrant and deficient in nuclear fiber cells. These studies indicate that programmed ablation of specific cell types can be stably transmitted through the germ line.     

HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection

Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.     

Dissecting the genetic basis of maize deep-sowing tolerance by combining association mapping and gene expression analysis

Deep-sowing is an important method for avoiding drought stress in crop species,including maize.Identifying candidate genes is the groundwork for investigating the molecular mechanism underlying maize deep-sowing tolerance.This study evaluated four traits(mesocotyl length at 10 and 20 cm planting depths and seedling emergence rate on days 6 and 12) related to deep-sowing tolerance using a large maize population containing 386 inbred lines genotyped with 0.5 million high-quality single nucleotide ...     

Specific block of calcium channel expression by a fragment of dihydropyridine receptor cDNA

Although the structure of rabbit skeletal muscle dihydropyridine (DHP) receptor, deduced from cDNA sequence, indicates that this protein is the channel-forming subunit of voltage-dependent calcium channel (VDCC), no functional proof for this prediction has been presented. Two DNA oligonucleotides complementary to DHP-receptor RNA sequences coding for putative membrane-spanning regions of the DHP receptor specifically suppress the expression of the DHP-sensitive VDCC from rabbit and rat heart in Xenopus oocytes. However, these oligonucleotides do not suppress the expression of the DHP-insensitive VDCC and of voltage-dependent sodium and potassium channels. Thus, the gene for DHP receptor of rabbit skeletal muscle is closely related, or identical to, a gene expressed in heart that encodes a component of the DHP-sensitive VDCC. The DHP-sensitive and DHP-insensitive VDCCs are distinct molecular entities.     

A novel long non-coding RNA,DIR, increases drought tolerance in cassava by modifying stress-related gene expression

Cassava is an important tropical cash crop. Severe drought stresses affect cassava productivity and quality, and cause great economic losses in agricultural production. Enhancing the drought tolerance of cassava can effectively improve its yield. Long non-coding RNAs(lncRNAs) are present in a wide variety of eukaryotes. Recently, increasing evidence has shown that lncRNAs play a critical role in the responses to abiotic stresses. However, the function of cassava lncRNAs in the drought response r...     

The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut

Immunoglobulin A (IgA) is essential to maintain the symbiotic balance between gut bacterial communities and the host immune system. Here we provide evidence that the inhibitory co-receptor programmed cell death-1 (PD-1) regulates the gut microbiota through appropriate selection of IgA plasma cell repertoires. PD-1 deficiency generates an excess number of T follicular helper (T(FH)) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer's patches. Consequently, the IgAs produced in PD-1-deficient mice have reduced bacteria-binding capacity, which causes alterations of microbial communities in the gut. Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier.     

Restoration of auditory nerve synapses in cats by cochlear implants

Congenital deafness results in abnormal synaptic structure in endings of the auditory nerve. If these abnormalities persist after restoration of auditory nerve activity by a cochlear implant, the processing of time-varying signals such as speech would likely be impaired. We stimulated congenitally deaf cats for 3 months with a six-channel cochlear implant. The device used human speech-processing programs, and cats responded to environmental sounds. Auditory nerve fibers exhibited a recovery of normal synaptic structure in these cats. This rescue of synapses is attributed to a return of spike activity in the auditory nerve and may help explain cochlear implant benefits in childhood deafness.     

Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies

Targeted therapies that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway have shown promising anticancer activity, but their efficacy in the brain tumor glioblastoma multiforme (GBM) and other solid tumors has been modest. We hypothesized that multiple RTKs are coactivated in these tumors and that redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. Tumor cell lines, xenotransplants, and primary tumors indeed show multiple concomitantly activated RTKs. Combinations of RTK inhibitors and/or RNA interference, but not single agents, decreased signaling, cell survival, and anchorage-independent growth even in glioma cells deficient in PTEN, a frequently inactivated inhibitor of PI3K. Thus, effective GBM therapy may require combined regimens targeting multiple RTKs.