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Guillaume Postic Jean Solarz Cécile Loubière Janany Kandiah Jaysen Sawmynaden Frederic Adam Marie Vilaire Thibaut Léger Jean-Michel Camadro Daniella Balduino Victorino Marie-Claude Potier Eric Bun Gautier Moroy Alexandre Kauskot Olivier Christophe Nathalie Janel 《Journal of cellular and molecular medicine》2023,27(15):2228-2238
Down syndrome is the most common chromosomal abnormality in humans. Patients with Down syndrome have hematologic disorders, including mild to moderate thrombocytopenia. In case of Down syndrome, thrombocytopenia is not associated with bleeding, and it remains poorly characterized regarding molecular mechanisms. We investigated the effects of overexpression of Dyrk1A, an important factor contributing to some major Down syndrome phenotypes, on platelet number and bleeding in mice. Mice overexpressing Dyrk1A have a decrease in platelet number by 20%. However, bleeding time was found to be reduced by 50%. The thrombocytopenia and the decreased bleeding time observed were not associated to an abnormal platelet receptors expression, to a defect of platelet activation by ADP, thrombin or convulxin, to the presence of activated platelets in the circulation or to an abnormal half-life of the platelets. To propose molecular mechanisms explaining this discrepancy, we performed a network analysis of Dyrk1A interactome and demonstrated that Dyrk1A, fibronectin and fibrinogen interact indirectly through two distinct clusters of proteins. Moreover, in mice overexpressing Dyrk1A, increased plasma fibronectin and fibrinogen levels were found, linked to an increase of the hepatic fibrinogen production. Our results indicate that overexpression of Dyrk1A in mice induces decreased bleeding consistent with increased plasma fibronectin and fibrinogen levels, revealing a new role of Dyrk1A depending on its indirect interaction with these two proteins. 相似文献
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Purposeful provisioning of food to wild animals is a widespread and growing activity that has the potential to impact populations and communities. Nevertheless, studies assessing use of recreational feeders by free‐living birds during winter are surprisingly rare and largely limited to regions with continental climates characterized by freezing temperatures and snow cover. In contrast, there is little information available regarding bird use of feeders within warmer climates during winter, despite widespread recreational feeding in these areas. In this study, we quantified visitation patterns to bird feeders in a Mediterranean climate to evaluate the relationship between feeder use and several environmental variables known to influence supplemental feeder use in continental climates. We established a network of bird feeders in Corvallis, Oregon, USA, that were filled with black oil sunflower (Helianthus annuus) seeds and equipped with radio frequency identification (RFID) data loggers that recorded >315,000 visits by 70 individual Black‐capped Chickadees (Poecile atricapillus) across a 5‐month period (October 2016–March 2017). We found extensive variation in feeder use, with individuals averaging 1–406 feeder visits/day and using 1–9 of the 21 feeders that were available; individual variability was largely consistent during the course of our study. At the population level, we found that feeder use decreased from the start of our study, and this decline continued through the period when foraging was most limited by daylight, including the winter solstice. In contrast to theoretical predictions and empirical work in continental climates, we found that weather variables did not drive feeder use and that feeder visits peaked at mid‐day and gradually decreased until sunset. Our study indicates that individual‐level differences combined with seasonality to drive feeder use patterns, and we conclude that use of supplemental feeders during winter in Mediterranean climates appears to differ notably from feeder use in continental climates. 相似文献