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    Schade en schande

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    Contains fulltext : 315506.pdf (Publisher’s version ) (Open Access)Na ruim dertig jaar ervaring als advocaat en vijfentwintig jaar als curator overdenkt Bert Jansen op deze Blauwe pagina’s zijn werkend leven15 januari 20252 p

    RRAGD variants cause cardiac dysfunction in a zebrafish model

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    Item does not contain fulltextThis collection contains the raw data for "RRAGD variants cause cardiac dysfunction in a zebrafish model" which was published in AJP Heart and Circulatory Physiology in 2024, and a chapter in a PhD thesis. The raw data are in excel formats or as image files (PNG/JPEG). The Ras-related GTP-binding protein D (RRAGD) gene plays a crucial role in cellular processes. Recently, RRAGD variants found in patients have been implicated in a novel disorder with kidney tubulopathy and dilated cardiomyopathy. Currently, the consequences of RRAGD variants at the organismal level are unknown. Therefore, this study investigated the impact of RRAGD variants on cardiac function using a zebrafish embryo model. Furthermore, the potential usage of rapamycin, an mTOR inhibitor, as a therapy was assessed in this model. Zebrafish embryos were injected with RRAGD p.S76L and p.P119R cRNA and the resulting heart phenotypes were studied. Our findings reveal that overexpression of RRAGD mutants resulted in decreased ventricular fractional shortening, ejection fraction, and pericardial swelling. In RRAGD S76L-injected embryos, lower survival and heartbeat were observed, whereas survival was unaffected in RRAGD P119R embryos. These observations were reversible following therapy with the mTOR inhibitor rapamycin. Moreover, no effects on electrolyte homeostasis were observed. Together, these findings indicate a crucial role of RRAGD in cardiac function. In the future, the molecular mechanisms by which RRAGD variants result in cardiac dysfunction and if the effects of rapamycin are specific for RRAGD-dependent cardiomyopathy should be studied in clinical studies

    Survival of periodontal ligament myofibroblasts after short-term mechanical strain in rats and in vitro: Could myofibroblasts contribute to orthodontic relapse?

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    Contains fulltext : 317658.pdf (Publisher’s version ) (Open Access)OBJECTIVES: To investigate in vivo whether myofibroblasts formed in the PDL after exposure to short-term high experimental orthodontic forces in rats survive. To study in vitro whether human PDL fibroblasts can differentiate into myofibroblasts and survive when chemical or mechanical stimuli are removed. DESIGN: Nine 6-week-old male Wistar rats were used in this experiment. Rat molars were exposed to high but rapidly decreasing experimental orthodontic forces by applying a rubber band and analyzed for the presence of myofibroblasts using ASMA staining. In vitro, human periodontal ligament (PDL) fibroblasts were exposed to transforming growth factor β1 (TGFβ1) and/or mechanical stress and monitored for myofibroblast formation and survival after these stimuli were abrogated. RESULTS: In vivo exposure to orthodontic forces strongly induced myofibroblast formation in the stretched regions of the PDL. Furthermore, many PDL myofibroblasts remained present 6 days after exposure to these short-term high orthodontic forces. Human PDL fibroblasts were shown to differentiate into myofibroblasts after 2 days of TGFβ1 exposure and survive for at least 2 more days after removing chemical stimuli (TGFβ1) or mechanical strain. Under in vitro conditions, both TGFβ1 and mechanical strain for 3 days promoted (myo)fibroblast formation, and these cells persisted for 3 more days after the removal of both stimuli. CONCLUSIONS: PDL myofibroblasts survive after the removal of mechanical strain in vivo and in vitro. This supports the hypothesis that myofibroblasts, which form in response to mechanical strain and chemical cues in the periodontal ligament (PDL), play a role in relapse following orthodontic tooth movement.01 april 202

    Chatting your way to quitting: A longitudinal exploration of smokers' interaction with a cessation chatbot

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    Contains fulltext : 317079.pdf (Publisher’s version ) (Open Access)Background: Cigarette smoking poses a major public health risk, requiring scalable and accessible interventions. Chatbots offer a promising solution, given their potential in providing personalized, long-term interactions. Despite their promise, limited research has examined their efficacy and the intertwined relationship between user experience and effectiveness over an extended period of time. Methods: In this prospective, single-arm study, we developed and evaluated Roby, a 5-session chatbot intervention incorporating motivational interviewing and cognitive behavioral therapy to help smokers quit. Roby engaged Dutch adult smokers (N = 102) in conversations covering topics such as setting a quit date, managing withdrawal and cravings, and relapse prevention. The primary outcome was the continuous abstinence rate at the end of the intervention, and secondary outcomes included 7-day point prevalence abstinence, self-efficacy, and cravings. User engagement, therapeutic alliance, and interaction satisfaction were measured weekly, and the trajectory was analyzed using Linear Mixed Models. Results: Following an intention-to-treat principle, 18.6 % of participants achieved continuous abstinence, and 37.3 % achieved 7-day point prevalence abstinence. Self-efficacy significantly improved over the intervention, and cravings decreased over time. A slight decreasing trend was observed in engagement and satisfaction, likely due to a novelty effect. However, the decrease did not affect the intervention's outcomes. Conclusion: This study demonstrates the feasibility and initial usefulness of Roby, highlighting the potential for chatbots in long-term cessation support. Future research should further validate these findings with randomized controlled trials. Additional efforts should focus on monitoring and maintaining user experience in the long term to enhance effectiveness.9 p

    Dataset Shape transformations in peptide-DNA coacervates driven by enzyme-catalyzed deacetylation

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    Item does not contain fulltextBiomolecular condensates formed by liquid-liquid phase separation (LLPS) are important organizers of biochemistry in living cells. Condensate formation can be dynamically regulated, for example by protein binding or enzymatic processes. However, how enzymatic reactions can influence condensate shape and control shape transformations is less well understood. Here, we design a model condensate that can be formed by the enzymatic deacetylation of a small peptide by sirtuin-3 in the presence of DNA. Interestingly, upon nucleation condensates initially form gel-like aggregates that gradually transform into spherical droplets, displaying fusion and wetting. This process is governed by sirtuin-3 concentration, as more enzyme resulted in a faster aggregate-to-viscous liquid transformation of the condensates. We show that the aggregate-like nature of the early-stage condensates is linked to the presence of short, double-stranded DNA. The counterintuitive formation of aggregate-like, non-spherical condensates near the critical point is attributed to stronger bending of the DNA by oppositely charged peptides as the system moves away from the critical point, deeper in the two-phase region. Overall, this work shows that enzymes can induce shape transformations of condensates, and that condensate material properties do not necessarily inform about their stability. In this collection, you can find the data underlying this study

    Famine and 'hongersnood' as transnational memory. Literary legacies of the 1840s food crises in Ireland and the Netherlands

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    Contains fulltext : 311592.pdf (Publisher’s version ) (Open Access)16 p

    Gauge Theories from Noncommutative Manifolds

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    Contains fulltext : 314388.pdf (Publisher’s version ) (Open Access

    Zingeving en het mentaal welzijn van jongeren: De rol van de middelbare school

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    Item does not contain fulltext14 april 202

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