22 research outputs found

    A Novel Chemically Differentiated Mouse Embryonic Stem Cell-Based Model to Study Liver Stages of Plasmodium berghei.

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    Asymptomatic and obligatory liver stage (LS) infection of Plasmodium parasites presents an attractive target for antimalarial vaccine and drug development. Lack of robust cellular models to study LS infection has hindered the discovery and validation of host genes essential for intrahepatic parasite development. Here, we present a chemically differentiated mouse embryonic stem cell (ESC)-based LS model, which supports complete development of Plasmodium berghei exoerythrocytic forms (EEFs) and can be used to define new host-parasite interactions. Using our model, we established that host Pnpla2, coding for adipose triglyceride lipase, is dispensable for P. berghei EEF development. In addition, we also evaluated in-vitro-differentiated human hepatocyte-like cells (iHLCs) to study LS of P. berghei and found it to be a sub-optimal infection model. Overall, our results present a new mouse ESC-based P. berghei LS infection model that can be utilized to study the impact of host genetic variation on parasite development

    A Novel Chemically Differentiated Mouse Embryonic Stem Cell-Based Model to Study Liver Stages of Plasmodium berghei.

    Get PDF
    Asymptomatic and obligatory liver stage (LS) infection of Plasmodium parasites presents an attractive target for antimalarial vaccine and drug development. Lack of robust cellular models to study LS infection has hindered the discovery and validation of host genes essential for intrahepatic parasite development. Here, we present a chemically differentiated mouse embryonic stem cell (ESC)-based LS model, which supports complete development of Plasmodium berghei exoerythrocytic forms (EEFs) and can be used to define new host-parasite interactions. Using our model, we established that host Pnpla2, coding for adipose triglyceride lipase, is dispensable for P. berghei EEF development. In addition, we also evaluated in-vitro-differentiated human hepatocyte-like cells (iHLCs) to study LS of P. berghei and found it to be a sub-optimal infection model. Overall, our results present a new mouse ESC-based P. berghei LS infection model that can be utilized to study the impact of host genetic variation on parasite development

    Same but different? Measurement invariance of the PIAAC motivation-to-learn scale across key socio-demographic groups

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    Abstract Background Data from the Programme for the International Assessment of Adult Competencies (PIAAC) revealed that countries systematically differ in their respondents’ literacy, numeracy, and problem solving in technology-rich environments skills; skill levels also vary by gender, age, level of education or migration background. Similarly, systematic differences have been documented with respect to adults’ participation in education, which can be considered as a means to develop and maintain skills. From a psychological perspective, motivation to learn is considered a key factor associated with both skill development and participation in (further) education. In order to account for motivation when analyzing PIAAC data, four items from the PIAAC background questionnaire were recently compiled into a motivation-to-learn scale. This scale has been found to be invariant (i.e., showing full weak and partial strong measurement invariance) across 21 countries. Methods This paper presents further analyses using multiple-group graded response models to scrutinize the validity of the motivation-to-learn scale for group comparisons. Results Results indicate at least partial strong measurement invariance across gender, age groups, level of education, and migration background in most countries under study (all CFI > .95, all RMSEA < .08). Thus, the scale is suitable for comparing both means and associations across these groups. Conclusions Results are discussed in light of country characteristics, challenges of measurement invariance testing, and potential future research using PIAAC data

    Generation of functional hepatocytes by forward programming with nuclear receptors.

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    Funder: UK Regenerative Medicine PlatformFunder: Wellcome TrustFunder: Wellcome - MRC Cambridge Stem Cell Institute, University of CambridgeFunder: Chan Zuckerberg InitiativeProduction of large quantities of hepatocytes remains a major challenge for a number of clinical applications in the biomedical field. Directed differentiation of human pluripotent stem cells (hPSCs) into hepatocyte-like cells (HLCs) provides an advantageous solution and a number of protocols have been developed for this purpose. However, these methods usually follow different steps of liver development in vitro, which is time consuming and requires complex culture conditions. In addition, HLCs lack the full repertoire of functionalities characterising primary hepatocytes. Here, we explore the interest of forward programming to generate hepatocytes from hPSCs and to bypass these limitations. This approach relies on the overexpression of three hepatocyte nuclear factors (HNF1A, HNF6, and FOXA3) in combination with different nuclear receptors expressed in the adult liver using the OPTi-OX platform. Forward programming allows for the rapid production of hepatocytes (FoP-Heps) with functional characteristics using a simplified process. We also uncovered that the overexpression of nuclear receptors such as RORc can enhance specific functionalities of FoP-Heps thereby validating its role in lipid/glucose metabolism. Together, our results show that forward programming could offer a versatile alternative to direct differentiation for generating hepatocytes in vitro

    Veränderungen in der sozialen und ethnischen Zusammensetzung der Schülerschaft aus demografischer Perspektive

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    In diesem Beitrag wird untersucht, welche Veränderungen in der ethnischen und sozialen Zusammensetzung der Bevölkerung im Schul- und Vorschulalter festzustellen sind und welche Konsequenzen sich hieraus für die Bildungsbeteiligung und damit für die Entwicklung des Bildungsstands in der Bevölkerung ergeben könnten. Auf Basis der Mikrozensuserhebung 2008 können hinsichtlich der Herkunftsregion der Eltern mehrere Migrantengruppen identifiziert werden, in denen die Kinder trotz des niedrigen Bildungstands der Eltern und vergleichsweise geringer sozioökonomischer Ressourcen in der Familie größere Chancen auf einen Bildungsaufstieg haben als Kinder aus Familien ohne Migrationshintergrund. In bildungsfernen Familien ohne Migrationshintergrund finden sich hingegen eine geringere Tendenz zu aufstiegsorientierten Bildungsentscheidungen und eine stärkere Bindung des Bildungsverhaltens an die ökonomische und soziale Lebenslage. Die Analysen liefern Hinweise darauf, dass der bildungsbezogene Hintergrund und die sozioökonomischen Ressourcen in den Familien insgesamt bedeutender sind für die Entwicklung des Bildungsniveaus in der Bevölkerung als Merkmale der Zuwanderung und der ethnischen Herkunft. (DIPF/Orig.)In this paper, we examine current changes in the ethnic and social composition of the preschool and school aged population as well as the consequences these changes may have for educational participation and thus for overall educational attainment in the near future. Based on the micro-census 2008 survey, we identify groups of migrants by region of parents\u27 origin where children - despite low levels of parents\u27 education and comparatively few socioeconomic resources - have greater chances of upward educational mobility than non-migrant children. By contrast, children from less educated, nonmigrant families show a much lower tendency to be upwardly mobile, and educational choices are more closely tied to the economic and social background. Thus, our analysis provides evidence that educational background and socio-economic resources in the students\u27 families are of greater importance for the overall development of educational attainment in Germany than characteristics of migration and ethnicity. (DIPF/Orig.
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