1,720,954 research outputs found
Discovery of antiphage systems and the study of their cooperation to stop viral attacks
No full textBacteria possess a diverse array of innate immune mechanisms that protect them from invading genetic elements, such as bacteriophages (phages). In recent years, the discovery of over 152 distinct defence systems, and more expected to emerge, has broadened our understanding of bacteria-phage interactions. However, at the start of this doctorate, there was an absence of computational tools to systematically identify defence systems in prokaryotic genomes. Furthermore, many defence systems remain unexplored and lack functional understanding. Therefore, in this thesis, I present the development of a computational tool for the identification of defence systems named the Prokaryotic Antiviral Defence LOCator (PADLOC). PADLOC was subsequently used to identify defence-associated genes, leading to the identification of putative defence subtypes and the discovery of a new system named Hma. Several candidates were experimentally verified by me for anti-phage functionality, overall indicating that PADLOC can identify new defence systems. Additionally, I investigated the uncharacterised Kiwa system, which is associated with membrane defence mechanisms. I provide mechanistic insights into Kiwa, revealing that the transmembrane protein KwaA detects phage infection by sensing inhibition of the host RNA polymerase, leading to the release of the DNA-binding effector KwaB. I also discovered that anti-RecBCD proteins antagonise Kiwa, and consequently, discuss the coexistence of RecBCD and Kiwa in the cell, emphasizing their crucial roles in ensuring protection and highlighting the complexity of bacterial immunity. To gain further insights into Kiwa, I employed comparative genomics on closely related Kiwa-resistant phages resulting in the identification of several putative anti-Kiwa genes. The observation that closely related phages display diverse Kiwa susceptibility underscores the importance of defence systems in determining phage resistance. Finally, I discuss the molecular characterisation of a novel Restriction-modification-like system, named Ronin, which induces cell death upon activation by phage anti-RM proteins. Using single-molecule super-resolution microscopy, I present evidence that Ronin localises at the cellular membrane upon activation by the RM inhibitor ArdA, suggesting that its toxicity is exerted through a membrane function. Ronin employs a strategy reminiscent of eukaryotic immune systems, further highlighting the conservation of immune strategies across domains of life. Overall, my thesis describes the development of an accessible tool for the identification of defence systems and expands on our current knowledge of bacterial antiphage mechanisms. The advancement in our understanding of phage-host interactions significantly contributes to the wider scientific community for the development of effective phage therapies and applications in biotechnology
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types
No full textTo provide protection against viral infection and limit the uptake of mobile genetic elements, bacteria and archaea have evolved many diverse defence systems. The discovery and application of CRISPR-Cas adaptive immune systems has spurred recent interest in the identification and classification of new types of defence systems. Many new defence systems have recently been reported but there is a lack of accessible tools available to identify homologs of these systems in different genomes. Here, we report the Prokaryotic Antiviral Defence LOCator (PADLOC), a flexible and scalable open-source tool for defence system identification. With PADLOC, defence system genes are identified using HMM-based homologue searches, followed by validation of system completeness using gene presence/absence and synteny criteria specified by customisable system classifications. We show that PADLOC identifies defence systems with high accuracy and sensitivity. Our modular approach to organising the HMMs and system classifications allows additional defence systems to be easily integrated into the PADLOC database. To demonstrate application of PADLOC to biological questions, we used PADLOC to identify six new subtypes of known defence systems and a putative novel defence system comprised of a helicase, methylase and ATPase. PADLOC is available as a standalone package (https://github.com/padlocbio/padloc) and as a webserver (https://padloc.otago.ac.nz)
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
No full textWe 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.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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