1,721,032 research outputs found
Fetal programming in pregnancy-associated disorders:Studies in novel preclinical models
Get PDFHet prenatale leven wordt gekenmerkt door snelle groei en ontwikkeling van de foetus. Tijdens deze periode worden organen gevormd en de rijping van alle organen en weefsels gaat samen met een snelle groei van het lichaam. Dit is een zeer kritische periode in het mensenleven, omdat de omgeving tijdens de zwangerschap de fysiologie van de foetus kan vormen om het optimaal te laten functioneren in de rest van het leven. Blootstelling aan ongunstige omstandigheden in het vroege leven kan echter een langdurige nadelige invloed hebben op de fysieke en mentale gezondheid. Dit fenomeen wordt ‘foetale programmering’ of ‘Developmental Origins of Health and Disease’ hypothese genoemd. Tijdens de zwangerschap ondergaat het lichaam van de moeder verschillende lokale en systemische veranderingen in metabolisme, immunologie en hart en vaten. Deze veranderingen zorgen voor optimale groei en ontwikkeling van de foetus. Wanneer de beschikbaarheid van voedingsstoffen of het functioneren van de placenta niet optimaal is, zal dit leiden tot verminderde groei van de foetus en de ontwikkeling van zwangerschapscomplicaties. De meest voorkomende complicaties waarbij de intra-uteriene omstandigheden niet optimaal zijn, zijn pre-eclampsie, intra-uteriene groeivertraging en zwangerschapsdiabetes. Deze complicaties worden gekenmerkt door een complexe etiologie en kunnen het risico op de ontwikkeling van andere complicaties vergroten. Daarnaast wordt de foetus hier ook aan blootgesteld, wat leidt tot een verhoogd risico op cardiovasculaire en metabole aandoeningen later in het leven. Welke factoren tijdens de zwangerschap betrokken zijn bij deze foetale programmering is echter nog grotendeels onbekend. Het ontwikkelen van preklinische modellen voor zwangerschapscomplicaties is belangrijk om de effecten van verschillende factoren tijdens de zwangerschap op foetale programmering te onderzoeken. Het onderzoek beschreven in dit proefschrift focust op nieuwe modellen voor de meest voorkomende zwangerschapscomplicaties en het effect daarvan op de gezondheid van de foetus. De resultaten in dit proefschrift zouden nuttig kunnen zijn voor het evalueren van ernst van foetale programmering en het bepalen van klinisch beleid op dit gebied. In dit proefschrift laten we nieuwe preklinische modellen van zwangerschapscomplicaties zien die waardevol zijn voor het bestuderen van foetale programmering als gevolg van een niet-optimale intrauterine omgeving. Deze modellen zijn zeer belangrijk om de mechanismen die een rol spelen in het beïnvloeden van levenslange gezondheid te ontrafelen. Het achterhalen van deze mechanismen kan helpen om selectieve en geslachtsspecifieke diagnostische en therapeutische middelen te ontwerpen om nadelige foetale programmering tegen te gaan. De modellen die in dit proefschrift beschreven worden benaderen het klinische verloop van de zwangerschapscomplicaties met als doel de hiaten in translationeel onderzoek naar foetale programmering te overbruggen
More than just a gut instinct-the potential interplay between a baby's nutrition, its gut microbiome, and the epigenome
No full text<p>Substantial evidence links early postnatal nutrition to the development of obesity later in life. However, the molecular mechanisms of this connection must be further elucidated. Epigenetic mechanisms have been indicated to be involved in this process, referred to as metabolic programming. Therefore, we propose here that early postnatal nutrition (breast and formula feeding) epigenetically programs the developing organs via modulation of the gut microbiome and influences the body weight phenotype including the predisposition to obesity. Specifically, the early-age food patterns are known to determine the gross composition of the early gut microbiota. In turn, the microbiota produces large quantities of epigenetically active metabolites, such as folate and short chain fatty acids (butyrate and acetate). The spectrum of these produced metabolites depends on the composition of the gut microbiota. Hence, it is likely that changes in gut microbiota that result in altered metabolite composition might influence the epigenome of directly adjacent intestinal cells, as well as other major target cell populations, such as hepatocytes and adipocytes. Nuclear receptors and other transcription factors (the PPARs, LXR, RXR, and others) could be physiologically relevant targets of this metabolite-induced epigenetic regulation. Ultimately, transcriptional networks regulating energy balance could be manipulated. For these reasons, we postulate that early nutrition may influence the baby epigenome via microbial metabolites, which contributes to the observed relationship between early nutrition and adult obesity.</p>
Towards the mechanism of early-life programming: Consequences of a maternal western diet
Get PDFMaternal diet is associated with the development of metabolism-related and other diseases in the offspring. Underlying mechanisms and molecular markers are only starting to be revealed. In this research project, we explored the physiological and molecular impact of maternal western-style diet on the development of the offspring. Mice were exposed to either a low fat/low cholesterol diet (LFD) or a western-style high fat/high cholesterol diet (WSD) before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at different developmental stages. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. Exclusively male offspring had significantly higher body weight and a non-alcoholic fatty liver-phenotype upon maternal WSD. We conclude that maternal WSD affects physiological parameters and induces vital changes in the molecular profile of the liver in offspring. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity, which in part might be related to a differential development of the placenta. We describe that the labyrinth diameter is larger in male placentas compared to the female placentas, which let us speculate that the male placenta supports transport of excess maternal nutrients to the male fetus. In addition we studied DNA methylation changes that might facilitate programming effects to persist into adulthood. In our mice we found a core set of specific methylation patterns corresponding to human steatohepatitis
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
Placental particles in pregnancy and preeclampsia: A comparative investigation of the function of syncytiotrophoblast microvesicles versus exosomes during pregnancy and preeclampsia
Get PDFExtracellulaire vesikels (EV) zijn kleine, membraan-omhulde blaasjes die worden geproduceerd door verschillende soorten cellen, zoals b.v. endotheel cellen, thrombocyten of immuun cellen. Zij zijn te vinden in alle lichaamsvloeistoffen (b.v. in bloed) in fysiologische en pathofysiologische omstandigheden. Uniek tijdens de zwangerschap zijn de EV van de buitenste laag van de foetale placenta, de syncytiotrofoblast (STB). Er wordt gedacht dat deze STB EV een rol zouden kunnen spelen in de maternale immunologische en hemostatische aanpassingen tijdens de zwangerschap. STB EV worden verondersteld ook betrokken te zijn bij de pathofysiologie van speciefieke zwangerschapscomplicaties, zoals pre-eclampsie (PE). PE wordt gekenmerkt door zwangerschapshypertensie en proteïnurie optredend in de tweede helft van de zwangerschap. Pathofysiologisch wordt bij PE ook o.a. een sterker geactiveerde ontstekingsrespons gezien, in vergelijking met de gezonde zwangerschap en meer coagulopathieën. In dit proefschrift wordt aangetoond dat de placentaire STB EV immunologische en pro-coagulatante eigenschappen hebben. Immunologische eigenschappen worden waargenomen met STB EV uit zowel normale als pre-eclamptische placenta, terwijl pro-coagulatante eigenschappen alleen worden waargenomen door STB EV van de hypoxische placenta (als model voor de pre-eclamptische placenta). Ook suggereren onze resultaten dat STB EV van de normale placenta een rol spelen in de adaptaties van de immuun response aan de zwangerschap, zoals activatie van de ontstekingsresponse en inductie van regulatoir lymfocyten. Maar tijdens PE worden niet de immuunregulerende lymfocyten geinduceert. Dit zou kunnen betekenen dat bij PE patiënten STB EV de onstekingsrespons indirect versterkt wordt omdat zij geen verhoogd aantal regulatoire lymfocyten cellen kunnen induceren
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
- …
