1,721,065 research outputs found

    INTERACTION BETWEEN THE HYPOXIA INDUCIBLE FACTOR 1 ALPHA AND THE HUMAN POLYOMAVIRUS BK: A RISK FACTOR FOR THE DEVELOPMENT OF POLYOMAVIRUS ASSOCIATED NEPHROPATHY

    Full text link
    Polyomaviruses are nonenveloped viruses with an icosahedral capsid of about 40-45 nm in diameter. The human polyomavirus BK (BKV) is a member of the Polyomaviridae family detected in 1971 in the urine of an immunosuppressed renal transplant recipient who developed ureteric stenosis. BKV has a worldwide seroprevalence of about 90%. After the primary infection, BKV establishes a life-long latency within the urogenital tract. The severe immunological impairment occurring in transplant kidney recipients leads to BKV reactivation that may result in the polyomavirus associated nephropathy (PVAN). During transplantation, kidney is subjected to hypoxic conditions, driven by the action of Hypoxia Inducible Factor (HIF). It has been proved that HIF isoform-1α (HIF-1α) may interact with several viruses, but till now there are no evidences regarding the interaction between BKV and HIF-1α. In the present study, we aimed to achieve a better understanding about the relation between BKV infection and hypoxia conditions in kidney cells in case of transplantation. Firstly, 17 kidney paraffin-embedded tissue samples were collected from kidney transplant patients, who developed or not PVAN (PVAN and NOT PVAN group) and from a control group in order to evaluate HIF-1α expression levels in vivo. Total RNA was extracted from paraffin embedded tissues, reverse transcripted into cDNA and HIF-1α expression was measured by means of a qualitative Real Time PCR. Then, in vitro experiments were conducted using the VERO cell line to evaluate the possible interaction between the BKV promoter and HIF-1α. Luciferase and Chromatin Immunoprecipitation (ChIP) assays were performed on BKV transfected VERO cells, to verify the interaction between the viral promoter and HIF-1α. In parallel, to clarify the nature of the interaction between HIF-1α and the BKV promoter, the sequences were in silico analyzed using BLASTN 2.2.32+ software to find whether one or more hypoxia response elements (HRE) core sequences were present in the BKV promoters. Finally, the effect of hypoxia on BKV replication was assessed by evaluating BKV replication in BKV infected VERO cells, treated and not treated with the hypoxia mimic Cobalt Chloride (CoCl2). The HIF-1α expression level resulted 13.6 folds higher in PVAN tissues than in the control group while no differences were observed between the NOT PVAN tissues and the control group. Luciferase assay showed that the presence of HIF-1α stabilized the BKV promoter, increasing its activity from 2-folds to 6-folds (p<0.05) in transfected cells. ChIP assay showed a physical interaction between HIF-1α and the BKV promoter. BLASTN analysis showed no match between HRE sequence and the BKV promoter sequences, confirming that no binding sites for HIF-1α are present in the viral promoter. Finally, data obtained from BKV infected VERO cells revealed that BKV viral load was 5-fold increased in CoCl2 treated cells compared to not treated infected cells. These data, taken together, are significant to define the role of hypoxic stress in BKV replication after renal transplantation. In particular, it can be concluded that the replication of this opportunistic virus, mainly due to immunosuppressive therapy, is furthermore stimulated and favorite by HIF-1α activation, driven by hypoxic conditions during transplantation. The experimental results suggested a hypothetical molecular mechanism underling this thesis, which can be outlined as follows: cellular response to hypoxic environment prevents HIF-1α proteasomal degradation, allowing the creation of a HIF-1 active complex. This complex translocates to the nucleus where it binds to the BKV promoter, stimulating the transcription of viral genes and promoting the BKV replication. If confirmed by further experiments, this scenario may have important clinical implications: exposition to hypoxia during renal transplantation process should be considered as a crucial risk factor for the development of PVAN. These findings could be translated into clinical practice, replacing modulation of HIF system with ex-vivo organ preservation technologies, such as extra-corporeal membrane oxygenation, or considering HIF-1α as a target to be inhibited, perhaps using RNA interference technology

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

    Full text link
    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

    Full text link
    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

    Full text link
    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

    No full text
    Nao informado
    corecore