1,721,199 research outputs found
Humane endotheelcellen, bacteriën en monocyten in S. aureus endocarditis: analyse van cellulaire interactie in vitro
No full textInfectieuze endocarditis (IE) gaat gepaard met ernstige complicaties en blijft nog steeds een klinische en diagnostische uitdaging. Resultaten voorgesteld in deze thesis beschrijven het endotheliale activatieproces, dat door S. aureus geïnitieerd wordt, één van de belangrijkste spelers in het veroorzaken van acute hartklepdeficiëntie.. Wij hebben nagegaan in welke mate fibronectine-bindende eiwitten van S. aureus verantwoordelijk zijn voor de adhesie van bacteriën aan endotheelcellen (EC). Vooreerst is de rol van FnBPs beschreven in het veroorzaken van een reeks pro-inflammatoire endotheliale reacties, dewelke resulteren in leukocytaccumulatie op endotheel, celbeschadiging en fibrinevorming. Door gebruik te maken van recombinante lactococci, die de membranaire staphylococcus molecules FnBPA en FnBPB tot expressie brengen, hebben we een zeer efficiënt inoculum-afhankelijk EC-infectiepatroon kunnen induceren in de resulterende stammen. Dit proces ging samen met EC-activatie, gemeten aan de hand van een opmerkelijke verhoging van de membraanexpressie van ICAM-1 en VCAM-1, alsook van de secretie van IL-8 en IL-6. De FnBPA-geïnduceerde membraanexpressie van ICAM-1 en VCAM-1 was vergelijkbaar met deze bekomen na stimulatie door IL-1, een krachtige inductor van endotheliale proinflammatoire reacties.FnBPA-positieve L. lactis induceerde eveneens een prominente weefselfactor-afhankelijke endotheelcel-gemedieerde stollingsreactie, d.m.v. verhoogde TF-antigeenspiegels en factor Xa activering. Daarenboven veroorzaakte FnBPA monocyt-adhesie, die samenviel met een significante toename van de hoeveelheid gevormd FXa.De ClfA-positieve L.lactis stam vertoonde een lage probabiliteit van endotheelcelinfectie, zonder aanleiding te geven tot endotheelcelactivatie. Uit deze bevindingen konden we besluiten dat S. aureus FnBPs, doch niet ClfA, in staat zijn om invasiviteit en pathogeniciteit te verlenen aan niet-pathogene L. lactis micro-organismen, hetgeen er op wijst dat bacterie-endotheelcelinteracties - bewerkstelligd door deze adhesie-molecules - voldoende zijn om inflammatie alsook procoagulante activiteit uit te lokken in geïnfecteerde endotheellocaties. Verder onderzoek was gericht op de bijdrage van enkelvoudige of gecombineerde FnBPA subdomeinen (A, B, C of D) op de bacterie-endothelelcelinteractie. Door gebruik te maken van een grote bibliotheek van enkelvoudige L. lactis-geëxprimerende FnBPA (sub)domeinen, al dan in combinatie, hebben we aangetoond dat domeinen met Fn-bindende activiteit nodig, doch voldoende waren om typische EC-reacties uit te lokken. FnBPA subdomeinen CD (aa 604-77) of A4+16 (aa 432-559) zijn betrokken in bacteriële adhesie aan ECs, hetgeen correleert met de mogelijkheid van deze fragmenten om een uitgesproken stijging te bewerksteligen in EC-membraaanexpressie van ICAM-1 en VCAM-1 en van de secretie van het chemokine IL-8, zowel als van een opgereguleerde weefselfactor-afhankelijke endotheelcel-gemedieerde stollingsinductie. Daarenboven tonen onze data dat één enkele Fn-bindende module volstaat voor maximale stimulatie van endotheliale en procoagulante responsen.Samengevat leveren deze bevindingen bijkomende inzichten in de rol die S. aureus FnBPA speelt in het vergemakkelijken van EC activatieprocessen. Onze resultaten belichtten de rol van tandem-gerepeteerde Fn-bindende modules, die geëxprimeerd kunnen worden, ofwel alleen of in combinatie, tijdens infectie en activatie van ECs. In het laatste deel van de thesis werden onze bevindingen doorgetrokken naar een endocarditis-model, met een invalshoek van weefselmodellering. Nieuwe therapeutische strategieën hebben immers als doel om de - aan klepvervanging geassocieerde - risicofactoren te minimaliseren en om de bio-compatibiliteit te verbeteren, dit via de constructie van autologe matrix-gebaseerde weefselengineering van hartkleppen. De interactie tussen deze matrices en bacteriën is tot op heden niet gekend, maar de potentiële rol van deze nieuw-gebouwde hartkleppen - en vooral hun matrix in het uitlokken van endovasculaire infecties -, lijkt belangrijk. Daarom hebben we de invloed van fibrine en collageen-gel matrix vergeleken op de bacterie-endothelcel interactie na contact met S. aureus, S. epidermidis en Streptococcus sanguis. De resultaten lieten zien dat S. aureus in hoge mate in staat is om endotheelcellen te infecteren, wanneer deze gekweekt worden op fibrine of collageen. Daartegenover staat dat S. aureus adhesie aan ECs significant lager uitvalt, wanneer endotheelcellen uitgeplaat werden, rechtstreeks op niet-gecoate weefselcultuurplaten. Infectie van ECs met S. sanguis en S. epidermidis was eerder beperkt en vertoonde geen verschil voor ECs op de drie oppervlakken. De bacteriële adhesie was vergelijkbaar voor beide gel-matrices en resulteerde in endotheliale proinflammatoire en procoagulante activering. We vonden een belangrijke EC-activering met markante expressie van ICAM-1 en VCAM-1, na S. aureus infectie, in vergelijking met de lage toename van EC-activering, na stimulatie door S. sanguis en S. epidermidis . De onderzoeksresultaten toonden geen verschil tussen fibrine- en collageengel, doch vergeleken met resultaten bekomen voor endotheelcellen, gekweekt op niet-gecoate cultuurplaten, werd een verlaagde monocyt-gemedieerde procoagulante activiteit waargenomen, ondanks een onveranderde monocytadhesie. Opregulering van anticoagulante cascades, zoals de productie van TFPI (Tissue Factor Pathway Inhibitor) of IL-10 zijn eveneens mogelijk.Dit onderzoek wijst dus op het belang van het type matrix als inductor van pathways, die leiden tot inflammatie, weefselschade en fibrine-afzetting, ter hoogte van geïnfecteerde endovasculaire lesies. Samengevat, verhoogt deze thesis onze inzichten in essentiële aspecten van bacteriële en cellulaire interacties in de vroege pathogenese van S. aureus geïnduceerde endocarditis. Voor de ontwikkeling van anti-adhesieve behandelings-strategieën, zijn deidentificatie van FnBPA als een centrale membraanmolecule en de bevinding dat ten minste één Fn-bindend domein nodig is, doch tevens volstaat om endotheelcellen te infecteren en, terzelfdertijd, proinflammatoire en procoagulante fenotypes uit te lokken, fundamenteel.status: Publishe
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
Chromosomale varianten in aangeboren hartafwijkingen
No full textCopy number variation in congenital heart defects The aim of this thesis was to advance our insight on copy number variation in thegenesis of congenital heart defects. The body of current knowledge on the genetics of CHD is scattered across publications, text books and genomic databases. To enhance the identification of chromosomal regions and genes recurrently linked to congenital heart defects, we developed a Wiki-based portal for standardized and curated integration of clinical and molecular data on CHD, termed CHDWiki, which is described in Part I of this thesis. In the first chapter we elaborate on the developmental process underlying CHDWiki, and we discuss on howthis Wiki knowledge and analysis portal can serve the broad community that is studying CHDs, ranging from the pediatric cardiologist and clinical geneticist to the basic investigator of cardiogenesis (Part I, Chapter 1 ) . Subsequently, all submicroscopic imbalances recurrently related to CHDs, compiled in CHDWiki, were evaluated in a systemic way todelineate overlapping imbalanced regions critical for heart development. We aimed to identify novel candidate genes for CHD within these regions, using computational gene prioritization tools. We provide an overviewof these results in chapter 2 (Part I, Chapter 2 ), and we elaborate on the delineation of 3 novel chromosomal CHD-related syndromes in chapter 3: the 16p13.3 microduplication syndrome, a novel recurrent 22q11 deletion and deletions on 10q22q23 (Part I, Chapter 3 ). Array comparative genomic hybridization is already widely used in a clinical setting for the diagnosis of individuals with congenital malformations . The interpretation of CNVs is challenging as infrequent disease-causing copy number changes should be distinguished from the abundant copy number variations without obvious major clinical significance. In Part II of this thesis, we discuss some of the challenges that arise upon the introduction of aCGH as a diagnostic tool in a clinical cardiogenetic setting, and introduce an algorithm for CNV interpretation (Part II, Chapter 1 ). We applied aCGH studies in large cohorts with syndromic CHD (Part II, Chapter 2 ) and sporadic non-syndromic CHD (Part II, Chapter 3 ). Based on our experience as well as those of others described in the literature, we outline the state-of-the-art and attempt toanswer a number of outstanding questions, such as the yield of aCGH in different patient populations, the added value of higher resolution arrays, and the existence of predictive factors in syndromic cases. Studies addressing the role of somatic copy number variation (CNV) in the genesis of congenital heart defects are scarce. In Part III of this thesis, we explore the occurrence of CNV differences in monozygotic twins discordant for the presenece of a congenital heart defect,as an illustrative model for chromosomal mosaicism in CHD.status: Publishe
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
Anti-platelet therapy abrogates platelet-assisted Staphylococcus aureus infectivity of biological heart valve conduits
No full textOBJECTIVE: Although recent advances in pulmonary valve replacement have enabled excellent hemodynamics, infective endocarditis remains a serious complication, particularly for implanted bovine jugular vein (BJV) conduits. METHODS: We investigated contributions by platelets and plasma fibrinogen to endocarditis initiation on various grafts used for valve replacement. Thus, adherence of Staphylococcus aureus and platelets to 5 graft tissues was studied quantitatively in perfusion chambers, assisted by microscopic analysis. We also evaluated standard antiplatelet therapy to prevent onset of S aureus endocarditis. RESULTS: Of all tissues, bovine pericardium (BP) showed the greatest fibrinogen binding. Perfusion of all plasma-precoated tissues identified BP and BJVwall with the greatest affinity for S aureus. Perfusions of anticoagulated human blood over all tissues also triggered more platelet adhesion to BP and BJVwall as single platelets. Several controls confirmed that both S aureus and platelets were recruited on immobilized fibrinogen. In addition, perfusions (and controls) over plasma-coated tissues with whole blood, spiked with S aureus, revealed that bacteria exclusively bound to adhered platelets. Both the platelet adhesion and platelet-mediated S aureus recruitment required platelet αIIbβ3 and coated or soluble fibrinogen, respectively, interactions abrogated by the αIIbβ3-antagonist eptifibatide. Also, standard antiplatelet therapy (aspirin/ticagrelor) reduced the adherence of S aureus in blood to BJV 3-fold. CONCLUSIONS: Binding of plasma fibrinogen to especially BJV grafts enables adhesion of single platelets via αIIbβ3. S aureus then attaches from blood to (activated) bound platelet αIIbβ3 via plasma fibrinogen. Dual antiplatelet therapy appears a realistic approach to prevent endocarditis and its associated mortality.sponsorship: This work was supported by the Research Fund KU Leuven (OT/14/097 to Heying and PF/10/014 to Hoylaerts) ; the Research Foundation-Flanders (12K0916N to Veloso) ; and the Association for European Paediatric and Congenital Cardiology (Junior Research Grant 2019 to Ditkowski) . Heying was sponsored by the Clinical Research Fund of UZ Leuven and the Flemish Research Foundation (FWO) . (Research Fund KU Leuven|OT/14/097, Research Fund KU Leuven|PF/10/014, Research Foundation-Flanders|12K0916N, Association for European Paediatric and Congenital Cardiology, Clinical Research Fund of UZ Leuven, Flemish Research Foundation (FWO))status: Publishe
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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