1,720,957 research outputs found
The role of non-typeable haemophilus influenzae biofilms in host-microbial and microbial-microbial interactions in chronic obstructive pulmonary disease
No full textNon-typeable Haemophilus influenzae is a commensal-turned-pathogen that has been implicated in several COPD patient cohorts and is associated with acute exacerbations and increased hospitalisation. It is currently unclear why NTHi represents such a challenging pathogen to treat, causing recurrent and chronic infections. Recently, there is growing evidence for the existence of NTHi in the biofilm lifestyle, conferring increased persistence, immune system and antimicrobial evasion and complex inter-specific interactions with other lung pathogens. Herein, I have developed a small airway epithelium NTHi coculture model system in order to investigate the host pathogen interactions that occur in the COPD small airways, as in improvement to current model systems which lack physiological relevance. I first demonstrated the detection of biofilm-like aggregations of NTHi by fluorescent in-situ hybridisation (FISH) in COPD lung biopsies and sputum expectorates. I adopted a bioinformatic approach to identify and shortlist 18 biofilm genes of interest (GOIs) in novel NTHi strains isolated from the COPD and healthy lung, including ST14, ST408 and ST253. These included genes functioning in quorum sensing, adhesion, surface modifications, immune system effectors, production of EPS matrix components and antimicrobial tolerance. I began to model NTHi biofilm growth and composition in a standard submerged model and progressed onto coculture NTHi with hSABCi-NS1.1 small airway epithelial (SAE) cells cultured at an air-liquid-interface (ALI), before applying these optimised methods to a primary donor small airways model of COPD. Using a range of fluorescent staining, SCLM and SEM techniques I categorised NTHi as an eDNA- and protein-rich EPS matrix biofilm-producing bacteria which aggregates at the epithelial surface; a mode of intracellular and paracellular invasion. RT-qPCR has shown these biofilms elicit sophisticated NTHi-strain dependent gene expression responses as well as host-dependent gene expression responses, and in particular the adhesins Hia, OMP P5, PilA as well as biofilm EPS matrix gene comE and antibiotic resistance gene β-lactamase are upregulated by NTHi in response to coculture with the small airway, highlighting targets for future therapeutic intervention. This small airway model was validated through a series of cytokine and viability assays which demonstrated that both models could launch a robust proinflammatory response against NTHi biofilms whilst maintaining barrier impermeability and low cytotoxicity. In addition, the model was successful in generating NTHi-derived outer membrane vesicles, which have emerged as an important vector of cell-cell communication, immune system modulation and potential transmission of biofilm-associated gene expression and coordination. Overall, I propose supporting evidence for NTHi as a biofilm in the COPD small airway based on these model systems. Thus, NTHi biofilms may explain the prevalence of chronic, recurrent infection
The role of non-typeable Haemophilus influenzae biofilms in Chronic Obstructive Pulmonary Disease
No full textNon-typeable Haemophilus influenzae (NTHi) is an ubiquitous commensal-turned-pathogen that colonises the respiratory mucosa in airways diseases including Chronic Obstructive Pulmonary Disease (COPD). COPD is a progressive inflammatory syndrome of the lungs, encompassing chronic bronchitis that is characterised by mucus hypersecretion and impaired mucociliary clearance and creates a static, protective, humid, and nutrient-rich environment, with dysregulated mucosal immunity; a favourable environment for NTHi colonisation. Several recent large COPD cohort studies have reported NTHi as a significant and recurrent aetiological pathogen in acute exacerbations of COPD. NTHi proliferation has been associated with increased hospitalisation, disease severity, morbidity and significant lung microbiome shifts. However, some cohorts with patients at different severities of COPD do not report that NTHi is a significant aetiological pathogen in their COPD patients, indicating other obligate pathogens including Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa as the cause. NTHi is an ubiquitous organism across healthy non-smokers, healthy smokers and COPD patients from childhood to adulthood, but it currently remains unclear why NTHi becomes pathogenic in only some cohorts of COPD patients, and what behaviours, interactions and adaptations are driving this susceptibility. There is emerging evidence that biofilm-phase NTHi may play a significant role in COPD. NTHi displays many hallmarks of the biofilm lifestyle and expresses key biofilm formation-promoting genes. These include the autoinducer-mediated quorum sensing system, epithelial- and mucus-binding adhesins and expression of a protective, self-produced polymeric substance matrix. These NTHi biofilms exhibit extreme tolerance to antimicrobial treatments and the immune system as well as expressing synergistic interspecific interactions with other lung pathogens including S. pneumoniae and M. catarrhalis. Whilst the majority of our understanding surrounding NTHi as a biofilm arises from otitis media or in-vitro bacterial monoculture models, the role of NTHi biofilms in the COPD lung is now being studied. This review explores the evidence for the existence of NTHi biofilms and their impact in the COPD lung. Understanding the nature of chronic and recurrent NTHi infections in acute exacerbations of COPD could have important implications for clinical treatment and identification of novel bactericidal targets.</p
Dataset supporting the University of Southampton Doctoral Thesis "The role of non-typeable haemophilus influenzae biofilms in host-microbial and microbial-microbial interactions in chronic obstructive pulmonary disease"
No full textDataset supporting the University of Southampton Doctoral Thesis "The role of non-typeable haemophilus influenzae biofilms in host-microbial and microbial-microbial interactions in chronic obstructive pulmonary disease".
The dataset includes zipped file:Data_-_PURE.zip
The research was funded by AstraZeneca.
To date, this data has not been associated with any publications. Publications are in progress.
This data is embargoed until 24/6/27
this data is under embargo until 24/6/27
This work was undertaken using a BBSRC iCASE PhD
studentship (BB/T508135/1) awarded for JW’s doctoral studies.
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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