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The regulation of expression of HERV-W MSRV and Syncytin by Tat differs according to cell differentiation and is mediated by TNF-alpha
No full textDisruption by SaCas9 endonuclease of HERV-Kenv, a retroviral gene with oncogenic and neuropathogenic potential, inhibits molecules involved in cancer and amyotrophic lateral sclerosis
Full text linkThe human endogenous retrovirus (HERV)-K, human mouse mammary tumor virus like-2 (HML-2) subgroup of HERVs is activated in several tumors and has been related to prostate cancer progression and motor neuron diseases. The cellular splicing factor 2/alternative splicing factor (SF2/ASF) is a positive regulator of gene expression, coded by a potent proto-oncogene, amplified, and abnormally expressed in tumors. TAR DNA-binding protein-43 (TDP-43) is a DNA/RNA-binding protein, negative regulator of alternative splicing, known for causing neurodegeneration, and with complex roles in oncogenesis. We used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, with the Cas9 system from Staphylococcus aureus (SaCas9), to disrupt the HERV-K(HML-2)env gene, and evaluated the effects on cultured cells. The tool was tested on human prostate cancer LNCaP cells, whose HERV-Kenv transcription profile is known. It caused HERV-K(HML-2)env disruption (the first reported of a HERV gene), as evaluated by DNA sequencing, and inhibition of env transcripts and proteins. The HERV-K(HML-2)env disruption was found to interfere with important regulators of cell expression and proliferation, involved in manaling, RNA-binding, and alternative splicing, such as epidermal growth factor receptor (EGF-R), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), SF2/ASF, and TDP-43. These novel findings suggest that HERV-K is not an innocent bystander, they reinforce its links to oncogenesis and motor neuron diseases, and they open potential innovative therapeutic options
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
The regulation of expression of HERV-W MSRV and Syncytin-1 by Tat differs according to cell differentiation and is mediated by TNFα
No full textThe expression of HERV-W/MSRV and Syncytin-1 endogenous retroviruses is regulated by cell differentiation and by exposure to HIV-Tat and TNF alpha
No full textEight percent of human DNA consists of retroelements, remnants of ancestral infections by exogenous retroviruses. The two members of the HERV-W family are MSRV (Multiple Sclerosis Associated Retrovirus) and ERVWE1 (able to produce only the Syncytin-1 env protein). MSRV and Syncytin-1 proteins have neuro-pathogenic and immune-pathogenic properties, as demonstrated in vitro and in vivo. We evaluated the expression of transcripts using specific primers that can selectively identify either MSRV-env or Syncytin-1, and the level of proteins using Western blotting assays.
To verify wheter MSRV and Syncytin-1 are activated by HIV-Tat, peripheral blood mononuclear cells (PBMC), monocyte-macrophages and astrocytes were either exposed to HIV-Tat and/or other treatments. The expression of transcripts and proteins of interest was evaluated by real-time RT-PCR and western blotting assays, respectively.
The results indicate that the basal expression of both elements varies with monocyte differentiation into macrophages, in which it is highly increased, as well as the response to Tat. Interestingly, while MSRV is always upregulated by Tat, Syncytin-1 is downregulated in monocytes and upregulated in macrophages deriving from the same monocytes. The opposite regulation by Tat of MSRVenv and Syncytin-1 occurs also in U87MG astroglioma cells, while in primary human fetal astrocytes (PHFA) Tat upregulates both elements. In these cells the earliest effect of Tat is the induction of TNFα. If PHFA cells are incubated with an anti-TNFα antibody, before the exposure to Tat, the blockade of endogenous TNFα abolishes Tat stimulation of MSRVenv and Syncytin-1 expression.
Within CNS, Tat-induced TNFα could induce high levels of the HERV-Ws, in macrophages and astrocytes, also without HIV replication. The indirect mechanism by which Tat activates the HERV-Ws through induction of TNFα could add a new piece to the puzzle of CNS pathogenesis, i.e. the HERV-Wenv contribute to the HIV-related neurodegeneration
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 linkWe 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 linkWe 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
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