2 research outputs found
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Eisler's Notes on Hollywood and the Film Music Project, 1935-42
In 1947, Hanns Eisler in collaboration with Theodor Adorno published a small but important book entitled Composing for the Films. The book represents a significant contribution to film studies, cultural criticism, and discipline of twentieth-century musical practice. It also provides on of the few extended historical texts from the 1940s that deconstructs Hollywood musical practice while probing the wider theoretical implications of motion picture music. Eisler's writings and The Film Music Project constituent one of the most astute examinations of Hollywood musical practice for its time
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Inherited causes of clonal haematopoiesis in 97,691 whole genomes.
Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2-4 and coronary heart disease5-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues