Recent advances in techniques for monitoring and perturbing neural populations have greatly enhanced our ability to study circuits in the brain. In particular, two-photon holographic optogenetics now enables precise photostimulation of experimenter-specified groups of individual neurons, while simultaneous two-photon calcium imaging enables the measurement of ongoing and induced activity across the neural population. Despite the enormous space of potential photostimulation patterns and the time-consuming nature of photostimulation experiments, very little algorithmic work has been done to determine the most effective photostimulation patterns for identifying the neural population dynamics.
View Article and Find Full Text PDFAims: Although current clinical therapies following myocardial infarction have improved patient outcomes, morbidity, and mortality rates secondary to ischemic and ischemia reperfusion (IR) injury remains high. Maintaining mitochondrial quality is essential to limit myocardial damage following cardiac ischemia and IR injury. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in regulating mitochondrial function and cardiac energy metabolism.
View Article and Find Full Text PDFAs the adoption and scope of genetic testing continue to expand, interpreting the clinical significance of DNA sequence variants at scale remains a formidable challenge, with a high proportion classified as variants of uncertain significance (VUSs). Genetic testing laboratories have historically relied, in part, on functional data from academic literature to support variant classification. High-throughput functional assays or multiplex assays of variant effect (MAVEs), designed to assess the effects of DNA variants on protein stability and function, represent an important and increasingly available source of evidence for variant classification, but their potential is just beginning to be realized in clinical lab settings.
View Article and Find Full Text PDFRepression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood.
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