HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia

<p>Abstract</p> <p>Background</p> <p>The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.</p> <p>Results</p> <p>During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains.</p> <p>Conclusion</p> <p>The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.</p

Empirical state of research on digital media in the classroom in inclusive and special education contexts. A systematic review

Bildung in einer digital geprägten Welt hat den Auftrag, zu einer aktiven, selbstbestimmten Teilhabe für alle Schülerinnen und Schüler beizutragen (KMK, 2016). Dazu bedarf es sowohl der curricularen Verankerung des Erwerbs einer umfassenden Medienkompetenz entlang der gesamten Schullaufbahn, als auch der gezielten und reflektierten Nutzung digitaler Medien im Sinne der Mediendidaktik. Im Kontext der Sonderpädagogik können digitale Medien unterschiedliche Funktionen zur Teilhabe aller Schülerinnen und Schüler erfüllen – darunter barrierefreie Zugänglichkeit, Anschluss an assistive Technologien, individuelle Förderung und Diagnostik. Der Artikel präsentiert ein systematisches Review zum Forschungsstand sonderpädagogischer und inklusiver Nutzung digitaler Medien im Unterricht, ordnet die Ergebnisse in den Diskurs um Digitalisierung unter der Perspektive von Inklusion ein und zeigt Forschungsdesiderate auf. Es stellt eine Ergänzung zu Quenzer-Alfred & Mertens et al. (im Druck) dar, die zuvor den empirischen deutschsprachigen Forschungsstand zu digitalen Medien für Schülerinnen und Schüler mit einem zusätzlichen oder einem sonderpädagogischen Förderbedarf im Hinblick auf Studien mit Peer-Review aggregierten und ein Desiderat in Bezug auf Grundlagenforschung mit Fokus auf eine inklusiv-mediale Unterrichtsforschung offenlegten. Ergänzend wurden nun empirische Originalstudien publiziert als Monografie, Abschlussarbeit, Berichte oder Artikel in Zeitschriften oder Konferenz- und Tagungsbänden ohne Peer-Review-Verfahren aggregiert. Auf Basis von sieben Einschlusskriterien wurden N=19 deutschsprachige Studien eingeschlossen. Die Mehrzahl der Studien fokussieren mit Lesen/Schreiben, Rechnen oder Lernen ausgewählte Bereiche schulischen Lernens, wobei der Medieneinsatz vielfach in Form des Einsatzes von Trainingssoftware erfolgt. Das Zusammenspiel der Potenziale von inklusiv-medialen Lernens im Klassenverband sowie der Medienkompetenzerwerb für alle Schülerinnen und Schüler ist hingegen kaum Gegenstand der Forschung. (DIPF/Orig.)Education in a digitally shaped world has the task to contribute to active, self-determined participation for all pupils (KMK, 2016). This requires the curricular anchoring of the acquisition of comprehensive media competence along the entire school career and the planned, targeted and reflected use of digital media in the sense of media didactics. In the context of special education, digital media can fulfil different functions for the participation of all pupils – including barrier-free accessibility, assistive technologies, individual support and diagnostics. The article presents a systematic review on the use of digital media in special needs education, places the results in the discourse on digitalization from the perspective of inclusion and identifies research desiderata. It is a supplement to Quenzer-Alfred & Mertens et al. (to be published), who previously aggregated empirical studies on digital media for pupils with additional or special educational needs with peer-review and revealed a desideratum for basic research focusing on inclusive-medium teaching. Additionally, empirical studies published as monographs, theses, reports or articles in journals or conference and conference proceedings without peer review were aggregated. Based on seven inclusion criteria N=19 German studies were included. The majority of the studies focused on selected areas of school learning, such as reading/writing, arithmetic or learning, whereby the use of media often took the form of the use of training software. The interplay of the potentials of inclusive media learning in the classroom as well as the acquisition of media competence for all pupils is hardly the subject of research. (DIPF/Orig.

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein Barr virus induced G protein coupled receptor 2 (EBI2) and its oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in livers of NASH patients by liquid chromatography-mass spectrometry and tested the role of the EBI2-7α,25-diHC-system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared to controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype related differences were observed in Ebi2-/- animals and animals with defects in the 7α,25-diHC synthesizing enzymes CH25H and CYP7B1 compared to wildtype littermate controls,arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by enhanced level of 7α- hydroxycholest-4-en-3-one, and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH

Strandsuppleties

status: publishe

Ground water level measurements in Flemish sea dikes

status: publishe