1,720,985 research outputs found
A proteomic study on faecal samples of patients with cystic fibrosis and their unaffected siblings
No full textCystic Fibrosis (CF) is the most common life threatening genetic disease in the Caucasian population. It affects multiple organs and has major consequences for the whole body. CF evolved from a strictly paediatric disease with poor prognosis to a chronic disease with a growing adult population for which the main focus of healthcare is to improve quality of life. Most of the CF research has focussed on the lung pathology. However, the disease also affects other parts of the body, including the gastrointestinal system. The human digestion system is associated with a complex microbiota and CF affects the gastrointestinal (GI) microbiota, both by biotic (altered intestinal environment) and abiotic (antibiotic treatment) factors. Furthermore, it is proposed that there is a link between GI dysbiosis, GI inflammation and pulmonary exacerbations. Insights in this GI dysbiosis and the host state (inflammation) is needed to adapt existing antimicrobial and anti-inflammatory therapies and/or develop alternative therapies for example through the administration of pre- and probiotics.
Previous studies have shown that patients with CF have GI dysbiosis, multiple antibiotic resistant strains are detected in the faeces of the patients, inflammation occurs in the GI tract and probiotics are promising as potential treatments for GI dysbiosis and inflammation. The major goals of the present study were to (i) obtain deeper insights in the composition and functionality of the faecal microbiota of patients with CF and (ii) to investigate the faecal proteome and inflammatory state of the GI-tract of the patients. We received faecal samples from children with CF and their unaffected siblings from the University Hospital of Leuven, in collaboration with Prof. K. De Boeck.
The first aim of this thesis was to develop a metaproteomic pipeline to obtain insights in the proteins of both the microbiota as well as the host. This ultimately led to a whole proteome extraction method, in combination with denaturing polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry. The protocol was optimised and the reproducibility of the protein extraction was demonstrated using the whole proteome fraction from faecal samples (three replicates) from a patient with CF and her sibling. We showed that the metaproteomic analysis provided relevant information on the inflammation status of CF patients in combination with information on the bacterial dysbiosis.
The results from this metaproteomic pipeline were used in the first study, a cross-sectional study to investigate the faecal dysbiosis by evaluating the proteins present in the faecal samples in combination with the host proteins. The faecal metaproteomes of fifteen patients with CF and their unaffected sibling were compared using label-free protein quantification methods in combined with computational and bioinformatics methods. The extracted proteins were digested with trypsin and the spectral counts of the peptides of this cross-sectional label-free proteomic study were statistically analysed. The retrieved peptides can be linked to the proteins and in total, 79 proteins were differentially detected between the patients with CF and their unaffected sibling. Of these proteins, 33 were detected more in the patients of which most were human and porcine proteins. The human proteins were associated with inflammation processes; the porcine proteins were administered to the patients via the pancreas enzyme replacement therapy, which is a standard care of treat for CF patients with pancreas insufficiency. In the siblings, 36 bacterial and 10 pancreas associated human proteins were more detected. Most of the bacterial proteins were involved in carbohydrate transport and metabolism.
The retrieved spectral counts of the peptides from the LC-MS/MS runs were also analysed by Unipept in combination with statistical analysis. From every peptide, the lowest common ancestor was determined and 100 bacterial taxonomic units were retrieved, which contain at least four peptides. The statistical analysis revealed 27 taxa with taxon-specific peptides, which were significantly different in the patients or the siblings. Of these, seven were detected at species level. A significant reduction of members of the Clostridium cluster IV (Faecalibacterium prausnitzii, Ruminococcus bromii and Subdoligranulum variabile) was noticed in the CF group compared with the unaffected siblings. In addition, a significant reduction in the abundance of bacteria involved in butyrate and propionate metabolism, including Roseburia inulinivorans was detected in patients with CF. Also, an increased abundance of Blautia gnava, Clostridium clostridioforme and Clostridium nexile was found to be associated with dysbiosis in CF. These seven aforementioned species could potentially be used as biomarkers of dysbiosis in CF. The state of intestinal dysbiosis is found in all patients with CF, indicating that there is a disturbed microbiota due to the disease related intestinal dysfunction and/or the frequent use of antibiotics. We found that not only the bacterial composition is different; also, the host proteome shows that there is a pronounced difference between the healthy host proteome and the CF host proteome.
In a second study, we developed a selected reaction monitoring (SRM) method for the validation of the potential biomarkers for intestinal dysbiosis in patients with CF. The faecal samples of four patients and their unaffected sibling were used to develop the method for the detection of two bacterial species that could serve as markers for the health state, i.e. Blautia gnava and Faecalibacterium prausnitzii. We targeted peptides from B. gnava, more frequently observed in the patients with CF and F. prausnitzii, which is typically observed at much lower abundance in the patients. Especially F. prausnitzii has the potential as a biomarker for the diagnosis of intestinal dysbiosis. This method could also be a promising alternative method to detect biomarkers of inflammation. By targeting these bacteria in combination with inflammation biomarkers, the infection could be monitored over time and efficiency of therapeutic interventions in the GI tract evaluated. The observed dysbiosis may represent a novel therapeutic target for the gastrointestinal complications in patients with CF. Following the administration of probiotics, the restoration of the intestinal microbiota could be monitored by using these biomarkers (taxa and inflammation biomarkers).
In a final study, we aimed to reveal if the state of dysbiosis in patients with CF is temporally or more stable over time. In a longitudinal study, four faecal samples from five patients with CF and their unaffected sibling were analysed with our metaproteomic approach. Using the spectral count data, we could perform two descriptive statistical analyses, i.e. clustering analysis and a canonical correspondence analysis (CCA) for both the Unipept taxonomic data and protein cluster data. The clustering results of the taxonomic data show that the faecal microbiota of the siblings is stable over time, only perturbations due to the administration of antibiotics (AB) influenced the taxonomic units present in these samples. Moreover, 6 months after AB treatment, the faecal microbiota was restored to a similar state as the initial composition. For the patients, who received multiple doses of AB, not all samples from the same patients clustered together. Based on the protein data, the patients and siblings cluster separately, indicating that different proteins were achieved from the patients than from the siblings. The CCA analysis revealed similar results. For the taxonomic data, the siblings cluster together and the patients are more scattered. This is indicating that in the unaffected siblings a core microbiota is present and much temporal variation in presence of taxonomic units is seen in the patients. For the protein cluster data, the CCA revealed that the patients cluster together, indicating that the same proteins are present in the different patients. These proteins are mostly involved in inflammation pathways and proteins originating from the pancreatic enzyme replacement therapy. The siblings are more scattered over the CCA of the protein clusters data, indicating that different bacterial proteins in the patients were detected witch might be due to undersampling.
In conclusion, the results from the cross-sectional and longitudinal data in this PhD provided the first metaproteomic data for the intestinal dysbiosis of patients with CF. The faecal dysbiosis that we noticed arised presumably from disease-associated factors such as abnormal mucus secretions and impaired digestion (all patients are pancreatic insufficient) and the destructive effects of the recurrent AB treatments. This all is accompanied with intestinal inflammation, which was found in the cross-sectional and longitudinal study. The intestinal inflammation also influences the bacterial dysbiosis and vice versa. The AB treatments of children with CF is necessary to prevent respiratory infectious outbreaks and a panel of biomarkers for dysbiosis could help in following the state of dysbiosis during CFTR corrector and potentiator therapy and/or treatments with AB. In addition, the panel of biomarkers could be used to follow the effects of probiotic therapies on the intestinal microbiota to improve the well-being of the patients with CF. In this respect, we observed a remarkable similarity with previous metaproteomic and metagenomic data of faecal samples from patients with inflammatory bowel disease, indicative for a common treatment strategy of the intestinal dysbiosis, using pre- or probiotics
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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