1,720,970 research outputs found
Mechanistic insights into phage resistance evolution by surface modification
Get PDFThe rise of antibiotic resistant bacteria is a global threat to public health and food security. Bacteriophages (phages) - viruses that kill and infect bacteria - are a promising alternative. Bacteriophages have successfully treated antibiotic resistant infections. However, as with antibiotics, phage resistance can also evolve. Bacteriophages attach to molecules on the bacterial outer membrane to infect the cell, e.g., lipopolysaccharides (LPS). A mutation in bacteria that modifies this surface molecule often leads to phage resistance. In this thesis, we study the mechanism of phage resistance evolution by surface modifications, using 30 Escherichia coli C LPS mutants resistant to ΦX174, an LPS-targeting phage (Chapter 3). We first evolved phages that can infect each of these initially resistant mutants. Some types of resistance are harder to overcome than others. I also investigated how LPS changes influence cell shape. LPS modifications can also impact antibiotic susceptibility, allowing for phage-antibiotic synergism. I measured susceptibility of LPS mutants to two antibiotics (Chapter 4). We find that deep rough mutants have increased chloramphenicol susceptibility but not gentamicin susceptibility. Hypothesis testing shows that treating E. coli C wildtype with ΦX174 and chloramphenicol eliminates deep rough mutants, and reduces phage resistance evolution. Our results illustrate the mechanism for phage-antibiotic synergism in our model system. In Chapter 5, I investigated the molecular basis of altered antibiotic susceptibility in cell surface mutants. Finally, I studied effects of phage adaptation to host before treatment (Chapter 6). This thesis provides a framework to understand the evolutionary consequences of phage resistance. The insights can help design evolution-informed treatments with reduced phage resistance evolution
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
Evolutionary exploration of a bacterial LPS genotype to phenotype map with phages
Get PDFThe evolution of bacterial resistance-to-phage strategies, and the mechanisms by which phages adapt to overcome these strategies, are usually studied via evolution experiments in which phages are added to sensitive bacteria and allowed to co-evolve. While this top-down approach has improved our understanding of co-evolutionary dynamics, it underestimates the diversity of available evolutionary pathways. In this thesis work, I propose an evolutionary bottom-up approach to study the natural lipopolysaccharide (LPS) structure diversity in resistant E. coli C strains and the corresponding ΦX174 adaptation process. I first investigated the mutational causes responsible for ΦX174-resistance using whole-genome sequencing. All phage-resistant mutants carry at least one mutation in genes linked to core LPS biosynthesis, assembly or regulation. Based on which genes are mutated and the current knowledge of LPS biology, I predicted that these bacterial strains collectively produce eight different LPS structures. Then, I used serial transfer experiments to evolve ΦX174 against each resistant mutant and determined the set of mutations required to overcome resistance. ΦX174 overcomes LPS-based resistance via mutations in only two genes: the F gene involved in host recognition and the H gene involved in DNA injection. Finally, I tested my predicted LPS genotype to phenotype maps using multiple phage infection assays to qualitatively determine the host range of each evolved phage. I showed that my evolved ΦX174 strains are great biosensor tools that can discriminate different E. coli C resistant strains. I also demonstrated that the LPS diversity is much greater than predicted. Instead of eight LPS structures, my phage analysis suggests that there are at least 14 distinct LPS phenotypes. My approach allows a deeper understanding of bacteria-phage interactions essential for developing efficient phage therapies in the future
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
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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