1,720,994 research outputs found
A Virus-Packageable CRISPR System Identifies Host Dependency Factors Co-Opted by Multiple HIV-1 Strains
ABSTRACT At each stage of the HIV life cycle, host cellular proteins are hijacked by the virus to establish and enhance infection. We adapted the virus packageable HIV-CRISPR screening technology at a genome-wide scale to comprehensively identify host factors that affect HIV replication in a human T cell line. Using a smaller, targeted HIV Dependency Factor (HIVDEP) sublibrary, we then performed screens across HIV strains representing different clades and with different biological properties to define which T cell host factors are important across multiple HIV strains. Nearly 90% of the genes selected across various host pathways validated in subsequent assays as bona fide host dependency factors, including numerous proteins not previously reported to play roles in HIV biology, such as UBE2M, MBNL1, FBXW7, PELP1, SLC39A7, and others. Our ranked list of screen hits across diverse HIV-1 strains form a resource of HIV dependency factors for future investigation of host proteins involved in HIV biology. IMPORTANCE With a small genome of ~9.2 kb that encodes 14 major proteins, HIV must hijack host cellular machinery to successfully establish infection. These host proteins necessary for HIV replication are called “dependency factors.” Whole-genome, and then targeted screens were done to try to comprehensively identify all dependency factors acting throughout the HIV replication cycle. Many host processes were identified and validated as critical for HIV replication across multiple HIV strains
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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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The functional interplay between TNPO3, CPSF6 and HIV-1 CA
Lentiviruses can infect postmitotic cells, indicative of a role for the nucleocytoplasmic transport machinery. Genome-wide RNA interference screens identified transportin 3 (TNPO3) that may regulate human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIC) nuclear import but plays no role during murine leukemia virus (MLV) infection. Independently, TNPO3 was shown to bind HIV-1 integrase (IN), a PIC component, suggesting a potential mechanism for nuclear import. We demonstrated direct binding between TNPO3 and several retroviral INs, which did not correlate with TNPO3 dependency profiles of the respective retroviruses. Infectivity assays employing HIV-1/MLV chimeric viruses ascertained that the capsid (CA) domain, but not IN, was the functional determinant of TNPO3 dependence. A carboxy-terminal truncation mutant of the serine-arginine rich (SR) protein family member, cleavage and polyadenylation specific factor 6 (CPSF6), CPSF6-358, which lacks its RS domain, was shown to restrict HIV-1 PIC nuclear import. We demonstrated that CPSF6 interacts with HIV-1 CA, and a single point mutation in CA, Asn74Asp (N74D), abolished this interaction. N74D also rendered HIV-1 TNPO3-independent and impaired cyclophilin A (CypA) binding to CA. The CA:CPSF6 binding interface, as described in a partial co-crystal structure, defined a surface pocket on CA that faces the CA hexamer:hexamer interspace. Infectivities and CA binding profiles of CA mutants within this pocket or with aberrant CypA-related phenotypes were assessed to compare their CPSF6-358 sensitivity and TNPO3 dependence, which largely correlated. We showed an overall correlation between the CPSF6/CPSF6-358 binding profiles of these HIV-1 CA mutants and their CPSF6-358 sensitivity, whereas TNPO3 binding and TNPO3 dependence did not correlate. Based on similar infectivity profiles of CA mutants and the loss of the RS domain from CPSF6-358 we tested for a direct interaction between CPSF6 and TNPO3. We demonstrated specific binding between recombinant TNPO3 and the CPSF6.RS domain. Mutagenesis experiments suggested a multicontact binding interface. The interaction was downmodulated by Ras-related nuclear protein (Ran)-GTP, indicating that CPSF6 is a bona fide import substrate of TNPO3. Our results support a model where TNPO3 regulates nuclear CPSF6 localization and that in its absence CPSF6 may restrict infection by directly interacting with HIV-1 CA at the hexamer:hexamer interface
Dispelling the Myths Behind First-author Citation Counts
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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