80 research outputs found

    The functions of herpesvirus-encoded microRNAs

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    Bioinformatic and direct cloning approaches have led to the identification of over 100 novel miRNAs expressed in DNA viruses, although the function of the majority of these small regulatory RNA molecules is unclear. Recently, a number of reports have now identified potential targets of viral miRNAs, including cellular and viral genes as well as an ortholog of an important immune-regulatory cellular miRNA. In this review, we will cover the identification and characterization of miRNAs expressed in the herpesvirus family and discuss the potential significance of their role in viral infection

    Experience of traumatic events in people with severe mental illness in a low-income country:a qualitative study

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    BACKGROUND: This study describes the trauma experiences of people with severe mental illness (SMI) in Ethiopia and presents a model of how SMI and trauma exposure interact to reduce functioning and quality of life in this setting.METHODS: A total of 53 participants living and working in a rural district in southern Ethiopia were interviewed: 18 people living with SMI, 21 caregivers, and 14 primary health care providers.RESULTS: Many participants reported that exposure to traumatic and stressful events led to SMI, exacerbated SMI symptoms, and increased caregiver stress and distress. In addition, SMI symptoms and caregiver desperation, stress or stigma were also reported to increase the possibility of trauma exposure.CONCLUSIONS: Results suggest it is incumbent upon health professionals and the broader health community to view trauma exposure (broadly defined) as a public health problem that affects all, particularly individuals with SMI

    A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 5 ' UTRs

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    Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3′ untranslated region (UTR). Using RNA induced silencing complex immunoprecipitation (RISC-IP) techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV) miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5′UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5′UTRs

    Global Pattern Search at Scale

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    In recent years, data collection has far outpaced the tools for data analysis in the area of non-traditional GEOINT analysis. Traditional tools are designed to analyze small-scale numerical data, but there are few good interactive tools for processing large amounts of unstructured data such as raw text. In addition to the complexities of data processing, presenting the data in a way that is meaningful to the end user poses another challenge. In our work, we focused on analyzing a corpus of 35,000 news articles and creating an interactive geovisualization tool to reveal patterns to human analysts. Our comprehensive tool, Global Pattern Search at Scale (GPSS), addresses three major problems in data analysis: free text analysis, high volumes of data, and interactive visualization. GPSS uses an Accumulo database for high-volume data storage, and a matrix of word counts and event detection algorithms to process the free text. For visualization, the tool displays an interactive web application to the user, featuring a map overlaid with document clusters and events, search and filtering options, a timeline, and a word cloud. In addition, the GPSS tool can be easily adapted to process and understand other large free-text datasets

    Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

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    Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

    Stellar Population and Kinematic Profiles in Spiral Bulges & Disks: Population Synthesis of Integrated Spectra

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    We present a detailed study of the stellar populations (SPs) and kinematics of the bulge and inner disk regions of eight nearby spiral galaxies (Sa-Sd) based on deep Gemini/GMOS data. The long-slit spectra extend to 1-2 disk scale lengths with S/N/Ang>=50. Several different model fitting techniques involving absorption-line indices and full spectrum fitting are explored and found to weigh age, metallicity, and abundance ratios differently. The SPs of spiral galaxies are not well matched by single episodes of star formation; representative SPs must involve average SP values integrated over the star formation history (SFH) of the galaxy. Our "full population synthesis" method is an optimised linear combination of model templates to the full spectrum with masking of regions poorly represented by the models. Our spiral bulges follow the same correlations of increasing light-weighted age and metallicity with central velocity dispersion as those of elliptical galaxies and early-type bulges found in other studies, but when SFHs more complex and realistic than a single burst are invoked, the trend with age is shallower and the scatter much reduced. In a mass-weighted context, all bulges are predominantly composed of old and metal-rich SPs. Bulge formation appears to dominated by early processes that are common to all spheroids, whether they currently reside in disks or not. While monolithic collapse cannot be ruled out in some cases, merging must be invoked to explain the SP gradients in most bulges. Further bulge growth via secular processes or "rejuvenated" star formation generally contributes minimally to the stellar mass budget. (Abridged)Comment: 38 pages, 19 figures, accepted for publication in MNRA

    Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

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    It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

    Herpes simplex virus immune evasion from antibody and complement

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    Herpes simplex virus type 1 (HSV-1) evades immunity mediated by antibody and complement. HSV-1 glycoproteins E (gE) and I (gI) encode a viral IgG Fc receptor (vFcγR) that blocks functions mediated by IgG. HSV-1 glycoprotein C (gC1) binds complement component C3b and inhibits the interaction of C5 and properdin (P) with Cab, blocking activation of both the classical and alternative complement pathways. Herpes simplex virus type 2 (HSV-2) encodes homologues of gE, gI, and gC, yet despite the significance of HSV-2 in human disease, relatively few studies address the complement evasion strategies used by this virus. In this dissertation, I examined the significance of HSV-2 gC (gC2) in immune evasion. Three independently derived wild type (WT) and gC2null virus pairs were compared to evaluate the mechanisms by which gC2 protects cell-free virus from complement-mediated neutralization; to determine whether gC2 protects infected cells from complement-mediated cell lysis; and to examine whether gC2 contributes to viral pathogenesis in vivo. Additional studies were performed to evaluate whether blocking immune evasion has potential therapeutic value in human immunodeficiency virus (HIV) patients. gC2 prevents complement-mediated neutralization induced by natural IgM antibody and the classical complement pathway. Natural IgM antibody in nonimmune human serum bound to HSV-2 gCnull virus and neutralized through a mechanism that required C1q and involved both C3 and C5, but not the formation of the membrane attack complex. Interestingly, HSV antibody-negative sera obtained from four individuals differed in potency of complement-mediated virus neutralization, indicating that innate immunity offers variable protection against HSV. gC2 contributes to viral pathogenesis. All gC2null viruses examined were significantly attenuated in the murine flank model of infection compared with WT strains. In C3 knockout mice, disease severity increased to levels comparable with WT virus for two HSV-2 strains, indicating that the virulence conferred by gC2 was through interaction with complement. Finally, studies examining complement and HSV antibody neutralization in HIV infected subjects support a significant contribution for gC and gE in preventing antibody and complement mediated neutralization, and indicate that gC and gE immune evasion domains shield critical neutralizing epitopes on viral glycoproteins involved in entry

    Herpes simplex virus immune evasion from antibody and complement

    No full text
    Herpes simplex virus type 1 (HSV-1) evades immunity mediated by antibody and complement. HSV-1 glycoproteins E (gE) and I (gI) encode a viral IgG Fc receptor (vFcγR) that blocks functions mediated by IgG. HSV-1 glycoprotein C (gC1) binds complement component C3b and inhibits the interaction of C5 and properdin (P) with Cab, blocking activation of both the classical and alternative complement pathways. Herpes simplex virus type 2 (HSV-2) encodes homologues of gE, gI, and gC, yet despite the significance of HSV-2 in human disease, relatively few studies address the complement evasion strategies used by this virus. In this dissertation, I examined the significance of HSV-2 gC (gC2) in immune evasion. Three independently derived wild type (WT) and gC2null virus pairs were compared to evaluate the mechanisms by which gC2 protects cell-free virus from complement-mediated neutralization; to determine whether gC2 protects infected cells from complement-mediated cell lysis; and to examine whether gC2 contributes to viral pathogenesis in vivo. Additional studies were performed to evaluate whether blocking immune evasion has potential therapeutic value in human immunodeficiency virus (HIV) patients. gC2 prevents complement-mediated neutralization induced by natural IgM antibody and the classical complement pathway. Natural IgM antibody in nonimmune human serum bound to HSV-2 gCnull virus and neutralized through a mechanism that required C1q and involved both C3 and C5, but not the formation of the membrane attack complex. Interestingly, HSV antibody-negative sera obtained from four individuals differed in potency of complement-mediated virus neutralization, indicating that innate immunity offers variable protection against HSV. gC2 contributes to viral pathogenesis. All gC2null viruses examined were significantly attenuated in the murine flank model of infection compared with WT strains. In C3 knockout mice, disease severity increased to levels comparable with WT virus for two HSV-2 strains, indicating that the virulence conferred by gC2 was through interaction with complement. Finally, studies examining complement and HSV antibody neutralization in HIV infected subjects support a significant contribution for gC and gE in preventing antibody and complement mediated neutralization, and indicate that gC and gE immune evasion domains shield critical neutralizing epitopes on viral glycoproteins involved in entry
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