1,721,032 research outputs found
Microbial Dynamics During Gut Inflammation And Infection
Get PDFThe gastrointestinal (GI) tract is colonized with complex microbial communities, known as the microbiota, that contribute to the health of the host. The intestinal microbiota plays an important role in determining susceptibility to enteric infection and therapeutic response to cancer treatment. The composition of the microbiota is known to influence the efficacy of a range of cancer therapies. We found that differences in the microbiota’s composition affects patients’ risk of developing inflammatory complications of immunotherapy. Increased representation of the Bacteroidetes phylum as well as B vitamin biosynthesis pathways are correlated with resistance to checkpoint-blockade-induced colitis. The microbiota’s composition is also known to impact the colonization density of antibiotic-resistant pathogens, an important cause of bacteremia in cancer patients receiving allogeneic hematopoietic stem cell transplants. We found that obligate anaerobes provide colonization resistance to Klebsiella pneumoniae, which is inhibited by short-chain fatty acids. Once colonized, enteric pathogens can evolve in the GI tract. This evolution can be tracked by the accumulation of single nucleotide polymorphisms (SNP) over time. In a mouse model of Enterococcus faecium colonization, SNPs were acquired at a rapid and regular rate, enabling us to study its diversification in real-time. Our work indicates that E. faecium can rapidly adapt in the gut by acquiring mutations in the pencillin-binding protein 5 while exposed to long-term ampicillin treatment
Cooperative Bacterial Interactions Mediate Resistance To Colonization By Intestinal Pathogens
Get PDFThe diverse microbial populations constituting the intestinal microbiota promote immune development, nutrient digestion and colonization resistance against invading pathogens. Due to their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized. In the past decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools and full genome characterization of several hundred commensal bacterial species have facilitated studies of the microbiota and revealed that differences in microbiota composition can be associated with a myriad of conditions and that the microbiota can be manipulated to prevent, reduce and even cure some of them. One of the most critical functions of the microbiota is to prevent the expansion of disease- causing organisms. Different bacterial species exert different roles within the intestine and therefore, the composition of the microbiota determines, in part, the level of resistance to infection. Perturbation of microbial communities with antibiotics renders the host susceptible to colonization by opportunistic antibiotic-resistant bacteria. The studies discussed in this dissertation aim to determine the impact that vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae, two common hospital-acquired infections, have on each other and on the host and to identify intestinal bacteria responsible for colonization resistance against VRE. We demonstrate that VRE and K. pneumoniae coexist within the intestine despite residing in very close proximity to each other and that colonization resistance against VRE can be mediated by two bacterial species despite antibiotic treatment. This work highlights the complex interplay between gut bacteria and has important implications for the development of new therapeutics to treat intestinal infections
Microbiota- And Pathogen-Specific Contributions To Clostridium Difficile Susceptibility And Virulence In The Mouse Model
No full textClostridium difficile is an anaerobic, gram-positive bacterium that is responsible for the majority of hospital-associated gastrointestinal infections. It has been recognized as a pathogen since the 1970s but more recently has become an urgent threat to public health. C. difficile produces two powerful toxins that disrupt the integrity of the colonic epithelium and induce a strong inflammatory response. Susceptible individuals experience symptoms that range from mild, self-limiting diarrhea to fulminant pseudomembranous colitis and even death. However, most healthy individuals are protected from C. difficile infections so long as they are able to maintain a diverse population of commensal bacteria in their gut. Disruptions to these commensals, often from antibiotic therapy, provide the niche C. difficile spores need to germinate, produce toxins, and cause disease. Current first-line therapy for infections is additional antibiotics that lead to a high risk of relapse. In fact, we found that short course antibiotic therapy leaves mice susceptible to additional infections in the days and weeks that the commensal microbiota spends recovering to pre-antibiotic levels. Beyond requiring disruptions to the microbiota before colonization, C. difficile is composed of hundreds of different strain subtypes. The variability in disease severity induced by each of these different subtypes has been hampered by diverse sources of human patient data and has confused the literature for years. We found that the mouse model could be used successfully to quantify the differences in disease burden of phylogenetically diverse C. difficile clinical isolates. Our results demonstrate that differences in observed virulence have less to do with the amount of toxin each isolate produces and more to do with its tolerance to secondary bile acids like lithocholic acid. In addition, whole genome sequencing allows us to identify groups of genes that are associated with highly lethal strains. This work emphasizes the need to evaluate the impact of antibiotic therapy and infecting strain when assessing and treating C. difficile infections
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
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
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