1,721,018 research outputs found
Improving virus taxonomy by recontextualizing sequence-based classification with biologically relevant data: the case of the Alphacoronavirus 1 species
The difficulties related to virus taxonomy have been amplified by recent advances in next-generation sequencing and metagenomics, prompting the field to revisit the question of what constitutes a useful viral classification. Here, taking a challenging classification found in coronaviruses, we argue that consideration of biological properties in addition to sequence-based demarcations is critical for generating useful taxonomy that recapitulates complex evolutionary histories. Within the Alphacoronavirus genus, the Alphacoronavirus 1 species encompasses several biologically distinct viruses. We carried out functionally based phylogenetic analysis, centered on the spike gene, which encodes the main surface antigen and primary driver of tropism and pathogenesis. Within the Alphacoronavirus 1 species, we identify Glade A (encompassing serotype I feline coronavirus [FCoV] and canine coronavirus [CCoV]) and Glade B (grouping serotype II FCoV and CCoV and transmissible gastroenteritis virus [TGEV]-like viruses). We propose this Glade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the Alphacoronavirus genus.
IMPORTANCE Our work focuses on improving the classification of the Alphacoronavirus genus. The Alphacoronavirus 1 species groups viruses of veterinary importance that infect distinct mammalian hosts and includes canine and feline coronaviruses and transmissible gastroenteritis virus. It is the prototype species of the Alphacoronavirus genus; however, it encompasses biologically distinct viruses. To better characterize this prototypical species, we performed phylogenetic analyses based on the sequences of the spike protein, one of the main determinants of tropism and pathogenesis, and reveal the existence of two subgroups or clades that fit with previously established serotype demarcations. We propose a new Glade designation to better classify Alphacoronavirus 1 members
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
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
Inhibition Of Influenza Virus And Human Parainfluenza I Virus Infection By The Protease Inhibitor Hai-2
Single-Particle Tracking Assays And Computational Tools For Studying Virus-Membrane Interactions
This dissertation discusses recent developments in single-particle tracking (SPT) assays and computational tools for studying the interaction between viruses and lipid membranes. Lipid membranes of host cells are effective barriers against foreign entities, but viruses have evolved strategies to bind to and penetrate through these membranes. The infection process involves a series of virus-host interactions such as 1) activation of viral proteins via host cell proteases, 2) binding of virus proteins to specific host cell receptors, 3) conformational changes of viral fusion proteins near the cell membrane, and 4) fusion of the cell and viral membranes. Building assays that can study these interactions is useful for expanding our knowledge on viruses and confirming the activity of antiviral compounds. With the combined usage of high-resolution microscopy and supported lipid bilayers, individual viruses can now be tracked as they undergo sequential steps of the virus infection process. Yet, the utility of this assay is limited by experimental design, image processing, and data analysis challenges. We have thus developed 1) an assay that can trigger virus membrane fusion rapidly, 2) a stochastic simulation model that explains major kinetics steps of the fusion process, 3) an image restoration algorithm that reveals virus particles in noisy SPT videos, and 4) a kinetic model that describes the "adhesion-strengthening" mechanism that viruses use to stably bind to membranes. We have tested the utility of these tools as we dissected the kinetics steps involved with the influenza virus and parvovirus infection process
Characterization of Ebolavirus Entry
Ebola virus disease is a global concern given its periodic occurrence, high lethality, and rapid spread, coupled with a lack of approved therapeutics and vaccines. New tools are needed to gain fundamental insight into the virus life cycle, particularly entry and fusion of the viral envelope with the host membrane, and to combat the spread of the disease. Some drugs that alter endo-lysosomal calcium can inhibit Ebola virus infection, hinting that calcium may play a role in Ebola virus entry. Calcium is known to mediate fusion of other enveloped viruses as well as synaptic vesicles (Chapter 1). Chapter 2 demonstrates that Zaire ebolavirus (EBOV) infection is increased in the presence of calcium and that increased infectivity is a result of calcium interacting with the EBOV fusion peptide. Calcium interacts with viral glycoprotein residues D522 and E540 to promote insertion of the fusion peptide into the host membrane. Notably, these residues are highly conserved across Filoviridae, suggesting that calcium-interfering drugs are important candidates in the search for antivirals against not only Ebola, but all filoviruses. Although receptor binding, low pH, removal of the glycan cap, and calcium have all been implicated in Ebola virus fusion, the exact trigger remains unknown. Techniques that enable the visualization of individual virions undergoing fusion can contribute substantially to clarifying the fusion trigger. Methods that track virions in live cells lend themselves to “top-down” experiments where individual cellular factors are knocked out either genetically or by drug treatment. Alternatively, biomimetic systems, such as those that monitor viral fusion with supported lipid bilayers, enable “bottom-up” approaches where factors are added in one by one. These approaches are discussed in detail in Chapter 3. Chapter 4 describes the construction of a biomimetic platform for investigating Ebolavirus fusion, including incorporation of the host receptor and control over exposure to potential fusion triggers. The speed at which new outbreaks can emerge necessitates new methods for preventing viral spread. Mammalian cell plasma membrane blebs functionalized with viral proteins are novel vaccine candidates (Chapter 5). They require less optimization than inactivated viruses or virus-like particles, and are particularly well-suited to viruses with heavily glycosylated proteins, like Ebola virus
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