Max Planck Institute for Medical Research

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    561975 research outputs found

    Analytical dual flip angle R1 calculation outside the small-angle regime

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    Purpose: To evaluate a new analytical estimator for R1 and apparent protondensity (A) from short-TR dual flip angle data which does not rely on the small flipangle approximation and can thus be applied to a broader range of data, especiallywhere relatively large flip angles are needed to achieve sufficient T1-weighting forR1 estimation.Theory and Methods: A rational approximation of the Ernst equation was de-rived for small R1·TR and rearranged to give analytical estimators of R1 and Afrom dual flip angle data. Unlike previously used analytical estimators, this methodrelies neither on the flip angles being small, nor the two TRs being equal or integermultiples of each other. R1 and A estimated using the novel method were com-pared to estimates using the conventional small angle approximation approach insimulations and data measured at 7T from six in vivo human participants and apostmortem chimpanzee brain. Test–retest scans of the six participants were usedto evaluate within-participant coefficients of variance (WCV) of R1 and A usingthe two methods.Results: The small angle approximation gave rise to a flip angle-dependent biasin all cases. This bias was not observed using the novel method, demonstratingits higher accuracy. There were only negligible differences in WCV between themethods, demonstrating that precision is preserved.Conclusion: The increase in accuracy and preservation of precision suggest thatthe novel method should be used instead of the current small flip angle method

    Psycholinguistic perspectives on face-to-face conversation

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    Bempedoic acid directly binds and activates PPARα

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    Bempedoic acid (BA) is a recently approved drug that lowers cholesterol and hepatic lipids, yet its mechanism of action remains incompletely understood. Here, we combine transcriptomic, biochemical, and structural approaches to show that BA directly binds to and activates peroxisome proliferator-activated receptor alpha (PPARα). BA treatment robustly induced PPARα signaling and fatty acid oxidation in primary hepatocytes and mouse liver. Through X-ray crystallography, we uncovered that BA binds to the ligand-binding domain of PPARα and stabilizes its active conformation. BA activated PPARα target genes independently of very-long-chain acyl-coenzyme A (CoA) synthetase (ACSVL1), the liver-enriched enzyme that converts BA to its bempedoyl-CoA form. Notably, BA-mediated induction of fatty acid oxidation required PPARα. Together, this work reveals direct PPARα activation as a key mechanism of BA action, providing a molecular basis for its lipid-lowering effects and suggesting broader therapeutic potential beyond the liver

    Wanting Greenland: When the Strong Stop Pretending

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    The US’s desire to have Greenland is deeply unpopular, whether in the US or in Greenland, observes Danish academic Erik Baark. Ultimately, US President Trump’s disregard for international law, treaties or organisations lays bare the US’s reversion to gunboat diplomacy, ushering in a new era of geopolitics of the mighty

    Malate matters: disrupting bacterial-type phosphoenolpyruvate carboxylase (BTPC) rewires tomato fruit development

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    Plant phosphoenolpyruvate carboxylases (PEPCs) are ubiquitously expressed as cytosolic Class-1 PEPC homotetramers composed of 107 kDa plant-type PEPC (PTPC) subunits that are highly sensitive to allosteric inhibition by malate. Class-2 PEPC heterooctameric complexes that are desensitized to malate inhibition also exist in certain sink tissues due to the interaction of a Class-1 PEPC with unrelated 118 kDa bacterial-type PEPC (BTPC) polypeptides. Class-2 PEPCs dynamically associate with the mitochondrial outer envelope and have been hypothesized to support sustained anaplerotic flux and respiratory CO₂ refixation in malate-rich sink tissues, including immature tomato fruit. The current study generated CRISPR-Cas9-edited tomato lines with targeted disruption of the BTPC gene and investigated the impact on fruit development, metabolism, and transcriptional regulation. Immunoblotting and co-immunoprecipitation confirmed the absence of BTPC polypeptides and Class-2 PEPC complexes in the edited lines. Fruits from the edited plants were 25% smaller and 40% lighter and required up to 10 additional days to complete ripening compared to the WT. Metabolomic analysis across ripening stages revealed substantial reductions in malate and citrate, with elevated sugars and amino acids, indicating reprogrammed carbon flux. RNA-seq data showed downregulation of genes for cell wall remodeling, sugar transport, and ethylene-responsive transcription factors. These results provide direct evidence that BTPC is essential for organic acid balance, sugar metabolism, and ripening regulation in tomato. Its absence perturbs metabolic homeostasis and developmental progression, positioning BTPC as a strategic target for enhancing fruit quality traits through genetic engineering

    A universal of human social cognition: Children from 17 communities process gaze in similar ways (advance online)

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    Theoretical accounts typically assume that key features of human socio-cognitive development are universal. This paper reports a large-scale cross-cultural study (17 communities, diverse ethnicities, N = 1,377, 709 female, mean = 5.50 years, collected March 2022 to January 2024) on gaze following in early childhood. To test for universality, cognitive processing signatures were derived from a computational model treating gaze following as social vector estimation. Results showed substantial variation between communities and individuals. Yet, the processing signature was found in all communities. Individual differences in performance were related to children’s familiarity with the data-collection device but not opportu-nities for social interaction. These results provide strong evidence for gaze following as a universal socio-cognitive process despite cultural and individual-level variation in absolute performance

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