826 research outputs found

    Breaking Up the C Complex Spliceosome Shows Stable Association of Proteins with the Lariat Intron Intermediate

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    Spliceosome assembly requires several structural rearrangements to position the components of the catalytic core. Many of these rearrangements involve successive strengthening and weakening of different RNA∶RNA and RNA∶proteins interactions within the complex. To gain insight into the organization of the catalytic core of the spliceosome arrested between the two steps of splicing chemistry (C complex), we investigated the effects of exposing C complex to low concentrations of urea. We find that in the presence of 3M urea C complex separates into at least three sub-complexes. One sub-complex contains the 5′exon, another contains the intron-lariat intermediate, and U2/U5/U6 snRNAs likely comprise a third sub-complex. We purified the intron-lariat intermediate sub-complex and identified several proteins, including U2 snRNP and PRP19 complex (NTC) components. The data from our study indicate that U2 snRNP proteins in C complex are more stably associated with the lariat-intron intermediate than the U2 snRNA. The results also suggest a set of candidate proteins that hold the lariat-intron intermediate together in C complex. This information is critical for further interpreting the complex architecture of the mammalian spliceosome

    Seroepidemiology of Toxoplasma gondii infection in psychiatric inpatients in a northern Mexican city

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    BACKGROUND: Patients with psychiatric disorders were found to show a high seroprevalence of Toxoplasma gondii infection. There is scarce information about the epidemiology of T. gondii infection in psychiatric patients in Mexico. Therefore, we sought to determine the prevalence of T. gondii infection and associated socio-demographic, clinical and behavioural characteristics in a population of psychiatric patients in Durango City, Mexico. Seroprevalence in patients was compared with that obtained in a control population. METHODS: One hundred and thirty seven inpatients of a public psychiatric hospital and 180 controls were examined for the presence of IgG and IgM antibodies against T. gondii by enzyme-linked immunoassay (Diagnostic Automation Inc., Calabasas, CA, USA). The control population consisted of blood donors of a public blood bank and elderly persons attending a senior center in the same city. Age in controls (42 years +/- 20.2) was comparable with that of the psychiatric patients (43.7 years +/-13.8) (p = 0.42). Socio-demographic, clinical and behavioral characteristics from the patients were also obtained. RESULTS: Anti-T. gondii IgG antibodies indicating latent infection with T. gondii was found in 25 (18.2%) of 137 psychiatric inpatients and 16 (8.9%) of 180 controls (p = 0.02). Ten (26.3%) of 38 schizophrenic patients had latent infection and this prevalence was also significantly higher than that observed in controls (p = 0.005). Prevalence of anti-T. gondii IgM antibodies was comparable among patients and controls (4.4% vs 2.2%, respectively, p = 0.22). Multivariate analysis showed that T. gondii infection in inpatients was positively associated with sexual promiscuity (adjusted OR = 15.8; 95% CI: 3.8–64.8), unwashed raw fruit consumption (adjusted OR = 5.19; 95% CI: 2.3–11.3), and a history of surgery (adjusted OR = 6.5; 95% CI: 2.6–16), and negatively associated with lamb meat consumption (adjusted OR = 0.26; 95% CI: 0.10–0.63). CONCLUSION: In the present study, psychiatric inpatients in Durango, Mexico, in general and schizophrenia inpatients in particular had a significantly higher prevalence of T. gondii infection than the control group. Results suggest that unwashed raw fruit consumption might be the most important route of T. gondii transmission in our psychiatric inpatients while lamb meat consumption the less important. Additional studies will have to elucidate the causative relation between infection with T. gondii and psychiatric disorders

    Leptonic and Semileptonic Decays of Charm and Bottom Hadrons

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    We review the experimental measurements and theoretical descriptions of leptonic and semileptonic decays of particles containing a single heavy quark, either charm or bottom. Measurements of bottom semileptonic decays are used to determine the magnitudes of two fundamental parameters of the standard model, the Cabibbo-Kobayashi-Maskawa matrix elements VcbV_{cb} and VubV_{ub}. These parameters are connected with the physics of quark flavor and mass, and they have important implications for the breakdown of CP symmetry. To extract precise values of Vcb|V_{cb}| and Vub|V_{ub}| from measurements, however, requires a good understanding of the decay dynamics. Measurements of both charm and bottom decay distributions provide information on the interactions governing these processes. The underlying weak transition in each case is relatively simple, but the strong interactions that bind the quarks into hadrons introduce complications. We also discuss new theoretical approaches, especially heavy-quark effective theory and lattice QCD, which are providing insights and predictions now being tested by experiment. An international effort at many laboratories will rapidly advance knowledge of this physics during the next decade.Comment: This review article will be published in Reviews of Modern Physics in the fall, 1995. This file contains only the abstract and the table of contents. The full 168-page document including 47 figures is available at http://charm.physics.ucsb.edu/papers/slrevtex.p

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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