1,721,021 research outputs found

    Editorial: Cell cycle control as a new therapeutic approach for SARS-CoV-2 infection

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    SARS-CoV-2 can manipulate cellular pathways, changing how well they can resist viral infection. Because of SARS-CoV-2 capacity to destroy p53, less cell death occurs in infected cells, which promotes viral replication, and p53 antiviral action is lost. Regarding this, p53 is a pleiotropic molecule associated with antiviral innate immune responses, which are specifically carried out by triggering apoptosis of infected cells and facilitating type I interferon (IFN) production/signaling. p53 consequently plays a crucial role in the setting of antiviral immunity, which may be why it is frequently targeted by viruses. By preventing virus-targeted cells from undergoing apoptosis, inflammation is made worse and a “cytokine storm” is produced. The major goals of the current pharmacological techniques to control SARS-CoV2 infection are to prevent viral binding and entry into human cells, to obstruct polyprotein complex translation and proteolysis, to obstruct viral RNA replication, and to limit viral release. The severity of COVID-19 disease is linked to heightened inflammatory responses, according to newly available clinical data, indicating that patient treatment plans should go beyond antiviral drugs

    Viral proteins as emerging cancer therapeutics

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    Viruses are obligatory intracellular parasites that originated millions of years ago. Viral elements cover almost half of the human genome sequence and have evolved as genetic blueprints in humans. They have existed as endosymbionts as they are largely dependent on host cell metabolism. Viral proteins are known to regulate different mechanisms in the host cells by hijacking cellular metabolism to benefit viral replication. Amicable viral proteins, on the other hand, from several viruses can participate in mediating growth retardation of cancer cells based on genetic abnormalities while sparing normal cells. These proteins exert discreet yet converging pathways to regulate events like cell cycle and apoptosis in human cancer cells. This property of viral proteins could be harnessed for their use in cancer therapy. In this review, we discuss viral proteins from different sources as potential anticancer therapeutics

    Virucidal efficacy of a novel silver-based disinfectant against SARS-CoV-2 Omicron BA.5

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    In this study we evaluated the antiviral activity of the Silver Barrier® disinfectant against SARSCoV-2. Silver Barrier® showed time- and concentration-dependent antiviral activity against SARSCoV-2. After 5 min contact time, Silver Barrier® at 0.002% showed a strong inhibitory effect (p<0.001), with a 2-fold reduction of viral genome copy numbers, and a robust suppression (94%) of SARS-CoV-2 infectivity. Considering the effects obtained in solution and within a very short time, Silver Barrier® stands as an excellent new candidate for the disinfection of work environments, especially at the healthcare level, where there are people at high risk of serious illnesses

    U94 gene of HHV-6 inhibits migration and angiogenesis in human endothelial cells

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    “Background”. Human Herpes virus 6 (HHV-6), a lymphotropic virus, infects and establishes a latent infection in endothelial cells (ECs). Following HHV-6 infection HHV-6 infection induces the loss of angiogenic properties in ECs as shown by inability to form capillary-like structures and seal wound scratches. The antiangiogenic effects observed in infected ECs are associated to the expression of HHV-6 U94/rep, a latency-associated gene. “Methods”. The full length U94 gene was cloned in the pVAX plasmid. Human umbilical ECs (HUVECs) were isolated, characterized, and cultured. HUVECs were transfected with an endotoxin-free U94-expressing pVAX plasmid by AMAXA. An empty U94 vector was used as control in all experiments. “Results”. Here we show that HUVECs expressing U94 are inhibited in their migratory capacity as demonstrated by “wound sealing” assay. Differently from cells nucleofected with empty pVAX, HUVECs expressing U94 were completely unable to repair a wound scratch carried out on a confluent cellular monolayer. Moreover, cells expressing U94 loss their ability to form a network of capillary-like structures when seeded on extracellular matrix (BME) coated plates. “Conclusions”. The capability of HHV-6 U94 to block both migratory and angiogenic capability of ECs may lead, if confirmed by experimental animal models, to the development of new therapeutic approaches in all those diseases in which an aberrant angiogenesis need to be modulated

    Binding to PI(4,5)P2 is indispensable for secretion of B-cell clonogenic HIV-1 matrix protein p17 variants

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    HIV-1 matrix protein p17 variants (vp17s) derived from non-Hodgkin's lymphoma (NHL) tissues of HIV-1-seropositive (HIV+) patients promote B-cell growth by activating the Akt signaling pathway. It is fundamental to understand the role played by vp17s in producing a microenvironment that fosters lymphoma development and progression. Therefore, we asked whether vp17s could be secreted from infected cells in their biologically active form. In this study, we show that two B-cell growth-promoting vp17s, NHL-a101 and NHL-a102, characterized by amino acid insertions at position 117 to 118 (Ala-Ala) or 125 to 126 (Gly-Asn), respectively, are secreted from HIV-1-infected Jurkat T cells during the active phase of viral replication. Secretion of biologically active vp17s also occurred in HeLa cells nucleofected with a plasmid expressing the entire Gag gene, following proteolytic cleavage of the Gag precursor polyprotein (Pr55Gag) by cellular aspartyl proteases. Binding of Pr55Gag to phosphatidylinositol-(4,5)-bisphosphate was indispensable for allowing the unconventional secretion of both wildtype p17 and vp17s. Indeed, here we demonstrate that inhibition of Pr55Gag binding to phosphatidylinositol-(4,5)bisphosphate by using neomycin, or its enzymatic depletion achieved by overexpression of 5ptaseIV, significantly impair the secretion of p17s. We also demonstrated that heparan sulfate proteoglycans were involved in tethering p17s at the cell surface. This finding opens up an interesting way for investigating whether tethered p17s on the surface of HIV-1 reservoirs may represent a likely target for immune-mediated killing

    Serosurvey in BNT162b2 vaccine-elicited neutralizing antibodies against authentic B.1, B.1.1.7, B.1.351, B.1.525 and P.1 SARS-CoV-2 variants

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    In this study, we show that BNT162b2 vaccine-elicited antibodies efficiently neutralize SARS-CoV-2 authentic viruses belonging to B.1, B.1.1.7, B.1.351, B.1.525 and P.1 lineages. Interestingly, the neutralization of B.1.1.7 and B.1.525 lineages was significantly higher, whereas the neutralization of B.1.351 and P.1 lineages was robust but significantly lower as compared to B.1 lineage. Following our findings, we consider that the BNT162b2 vaccine offers protection against the current prevailing variants of SARS-CoV-2

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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
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