AIDS-Kaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects

When grown in vitro, cells from Kaposi's sarcoma lesions of AIDS patients (AIDS-KS cells) constitutively release several growth promoting activities. When inoculated into nude mice, the AIDS-KS cells induce a KS-like lesion of mouse origin. Here it is shown that the AIDS-KS cells express messenger RNA for a complex mixture of cytokines that correlate with several of the biological activities of these cells. Basic fibroblast growth factor, which is a potent angiogenic factor, and interleukin-1 messenger RNAs are expressed at very high levels and seem to account for a large proportion of the activities, since their corresponding proteins are released in biologically active form into the culture media where they induce autocrine and paracrine growth effects.     

猪IGF2R基因多态性及其遗传印记

【目的】在猪IGF2R基因的外显子内寻找SNP,以SNP为遗传标记研究IGF2R基因的印记表达特征。【方法】选取3个品种243头瘦肉型商品猪为试验材料,以IGF2R基因为候选基因,通过PCR-SSCP对IGF2R基因多态性进行检测;选取IGF2R基因外显子48的SNP杂合子仔猪3头和成年猪1头,对脑、心脏、肝脏、脾、肾、肺、胃、胰、胸腺、膀胱、肌肉、舌、胎盘的组织器官mRNA产物分别进行RT-PCR-RFLP电泳和RT-PCR-SSCP电泳。【结果】IGF2R基因外显子48中有一个单核苷酸多态性位点,384位碱基由G突变为A,该位点为NspⅠ酶切位点;IGF2R的外显子48在3头仔猪和1头成年猪的主要组织器官仅表达母亲来源的等位基因。【结论】猪IGF2R基因呈母方表达、父方印记的遗传特征。     

Identification of virus-encoded microRNAs

RNA silencing processes are guided by small RNAs that are derived from double-stranded RNA. To probe for function of RNA silencing during infection of human cells by a DNA virus, we recorded the small RNA profile of cells infected by Epstein-Barr virus (EBV). We show that EBV expresses several microRNA (miRNA) genes. Given that miRNAs function in RNA silencing pathways either by targeting messenger RNAs for degradation or by repressing translation, we identified viral regulators of host and/or viral gene expression.     

Glia are essential for sensory organ function in C. elegans

Sensory organs are composed of neurons, which convert environmental stimuli to electrical signals, and glia-like cells, whose functions are not well understood. To decipher glial roles in sensory organs, we ablated the sheath glial cell of the major sensory organ of Caenorhabditis elegans. We found that glia-ablated animals exhibit profound sensory deficits and that glia provide activities that affect neuronal morphology, behavior generation, and neuronal uptake of lipophilic dyes. To understand the molecular bases of these activities, we identified 298 genes whose messenger RNAs are glia-enriched. One gene, fig-1, encodes a labile protein with conserved thrombospondin TSP1 domains. FIG-1 protein functions extracellularly, is essential for neuronal dye uptake, and also affects behavior. Our results suggest that glia are required for multiple aspects of sensory organ function.     

一只野生大熊猫死亡的病理学诊断

对一只死亡的野生雌性大熊猫进行了系统的病理学检查。主要病变：右侧下颌有一洞创深达皮下结缔组织；咽部食道与颈椎间有一形态不规则的大脓肿，颈下结缔组织中散布多个小脓肿，脓液灰白糊状；颌下、肺门等处淋巴结肿大化脓；右后肢腓骨和右侧第９，１０肋骨呈未愈合陈旧性骨折；肝门区有两个已钙化脓肿，肝细胞及间质局灶性变性坏死，少量炎细胞浸润；化脓性支气管肺炎，颈下皮下蜂窝织炎；多种组织器官内可见球菌样物质和微血栓。病理学诊断为脓毒败血性休克。     

Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage

Many mutations leading to human disease are the result of single DNA base pair changes that cannot be identified by Southern analysis. This has prompted the development of alternative assays for point mutation detection. The recently described ribonuclease A cleavage procedure, with a polyuridylic acid-paper affinity chromatography step, has been used to identify the mutational lesions in the hypoxanthine phosphoribosyltransferase (HPRT) messenger RNAs of patients with Lesch-Nyhan syndrome. Distinctive ribonuclease A cleavage patterns were identified in messenger RNA from 5 of 14 Lesch-Nyhan patients who were chosen because no HPRT Southern or Northern blotting pattern changes had been found. This approach now allows HPRT mutation detection in 50 percent of the cases of Lesch-Nyhan syndrome. The polyuridylic acid-paper affinity procedure provides a general method for analysis of low abundance messenger RNAs.     

公鸡生殖器官组织结构及其IL-1β和IL-6在生殖器官中的定位

【目的】IL-1β和IL-6在公鸡生殖器官免疫保护中发挥着重要的作用,研究拟揭示公鸡生殖器官的组织构造,以及定位IL-1β和IL-6在其生殖器官中的表达部位。【方法】通过苏木精-伊红染色方法,制作正常生理状态下公鸡生殖器官切片,观察公鸡生殖器官的组织构造以及生殖管道上皮细胞变化规律;同时采用免疫组化定位IL-1β和IL-6在生殖器官的部位。【结果】实验表明,附睾中的管道在公鸡生殖管道中占有很大比例,且生殖管道的上皮细胞的变化特征与其输送精液高度适应;IL-1β和IL-6主要定位于附睾近端输出管上,且IL-1β主要定位于短皱褶的近端输出管,IL-6主要定位于长皱褶的近端输出管上。【结论】结果表明附睾的输出管,尤其是近端可能是清除生殖道中的异常精子、脱落细胞等异物的主要部位。     

Isoform-specific modulation of Na+, K+-ATPase alpha-subunit gene expression in hypertension

Sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) is hypothesized to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and myocardial contractility. By means of RNA blot analyses of cardiac, aortic, and skeletal muscle RNAs in two rat hypertensive models, Na+,K+-ATPase alpha-subunit messenger RNA isoforms (alpha 2 and alpha 3) were shown to be deinduced in response to increased intravascular pressure. The changes were observed after 48 hours or more of experimental hypertension. Under these conditions, there is coordinate induction of another alpha isoform (alpha 1) and of beta-subunit messenger RNAs, probably in response to alterations in sodium flux rather than to elevated blood pressure.     

Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita

The DKC1 gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA). DKC1 is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations in ribosome modification might lead to cancer and other features of the disease remains unknown. Using an unbiased proteomics strategy, we discovered a specific defect in IRES (internal ribosome entry site)-dependent translation in Dkc1(m) mice and in cells from X-DC patients. This defect results in impaired translation of messenger RNAs containing IRES elements, including those encoding the tumor suppressor p27(Kip1) and the antiapoptotic factors Bcl-xL and XIAP (X-linked Inhibitor of Apoptosis Protein). Moreover, Dkc1(m) ribosomes were unable to direct translation from IRES elements present in viral messenger RNAs. These findings reveal a potential mechanism by which defective ribosome activity leads to disease and cancer.     

Multilineage potential of adult human mesenchymal stem cells

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.     

Role of microRNAs in plant and animal development

Small RNAs, including microRNAs (miRNAs) and short interfering RNAs (siRNAs), are key components of an evolutionarily conserved system of RNA-based gene regulation in eukaryotes. They are involved in many molecular interactions, including defense against viruses and regulation of gene expression during development. miRNAs interfere with expression of messenger RNAs encoding factors that control developmental timing, stem cell maintenance, and other developmental and physiological processes in plants and animals. miRNAs are negative regulators that function as specificity determinants, or guides, within complexes that inhibit protein synthesis (animals) or promote degradation (plants) of mRNA targets.     

Dendritic cell-induced memory T cell activation in nonlymphoid tissues

Secondary lymphoid organs are dominant sites of T cell activation, although many T cells are subsequently retained within peripheral tissues. Currently, these nonlymphoid compartments are viewed as sites only of effector T cell function, without the involvement of renewed induction of immunity via the interactions with professional antigen-presenting cells. We describe a method of reactivation of herpes simplex virus to examine the stimulation of tissue-resident T cells during secondary challenge. The results revealed that memory CD8+ T cell responses can be initiated within peripheral tissues through a tripartite interaction that includes CD4+ T cells and recruited dendritic cells. These findings lend evidence for the existence of a sophisticated T cell response mechanism in extra-lymphoid tissues that can act to control localized infection.     

Neuronal pp60c-src contains a six-amino acid insertion relative to its non-neuronal counterpart

Neuronal cells express a pp60c-src variant that displays an altered electrophoretic mobility and a different V8 peptide pattern relative to pp60c-src expressed in tissues of non-neuronal origin. To determine whether the neuronal form of pp60c-src is encoded by a brain-specific messenger RNA, a mouse brain complementary DNA (cDNA) library was screened with a chicken c-src probe and a 3.8-kilobase c-src cDNA clone was isolated. This clone encodes a 60-kilodalton protein that differs from chicken or human pp60c-src primarily in having six extra amino acids (Arg-Lys-Val-Asp-Val-Arg) within the NH2-terminal 16 kilodaltons of the molecule. S1 nuclease protection analysis confirmed that brain c-src RNA contains an 18-nucleotide insertion at the position of the extra six amino acids. This insertion occurs at a position that corresponds to a splice junction in the chicken and human c-src genes. The isolated c-src cDNA clone encodes a protein that displays an identical V8 peptide pattern to that observed in pp60c-src isolated from tissues of neuronal origin.     

Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA

MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interaction between miR-122 and the 5' noncoding region of the viral genome was revealed by mutational analyses of the predicted microRNA binding site and ectopic expression of miR-122 molecules containing compensatory mutations. Studies with replication-defective RNAs suggested that miR-122 did not detectably affect mRNA translation or RNA stability. Therefore, miR-122 is likely to facilitate replication of the viral RNA, suggesting that miR-122 may present a target for antiviral intervention.     

Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells

Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection. We identified endogenous siRNAs (endo-siRNAs), 21 nucleotides in length, that correspond to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to messenger RNAs (mRNAs); these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease Dicer-2 and the RNAi effector protein Argonaute2 (Ago2). We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line.