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Significant knowledge gaps exist regarding the responses of cells, tissues, and organs to organismal death. Examining the survival mechanisms influenced by metabolism and environment, this research has the potential to transform regenerative medicine, redefine legal death, and provide insights into life's physiological limits, paralleling inquiries in embryogenesis. 

RNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders; yet, the role of cell type–specific splicing and transcript-isoform diversity during human brain development has not been systematically investigated. In this work, we leveraged single-molecule long-read sequencing to deeply profile the full-length transcriptome of the germinal zone and cortical plate regions of the developing human neocortex at tissue and single-cell resolution. We identified 214,516 distinct isoforms, of which 72.6% were novel (not previously annotated in Gencode version 33), and uncovered a substantial contribution of transcript-isoform diversity—regulated by RNA binding proteins—in defining cellular identity in the developing neocortex. We leveraged this comprehensive isoform-centric gene annotation to reprioritize thousands of rare de novo risk variants and elucidate genetic risk mechanisms for neuropsychiatric disorders. 

Abstract The impact of extreme heat on crop yields is an increasingly pressing issue given anthropogenic climate warming. However, some of the physical mechanisms involved in these impacts remain unclear, impeding adaptation-relevant insight and reliable projections of future climate impacts on crops. Here, using a multiple regression model based on observational data, we show that while extreme dry heat steeply reduced U.S. corn and soy yields, humid heat extremes had insignificant impacts and even boosted yields in some areas, despite having comparably high dry-bulb temperatures as their dry heat counterparts. This result suggests that conflating dry and humid heat extremes may lead to underestimated crop yield sensitivities to extreme dry heat. Rainfall tends to precede humid but not dry heat extremes, suggesting that multivariate weather sequences play a role in these crop responses. Our results provide evidence that extreme heat in recent years primarily affected yields by inducing moisture stress, and that the conflation of humid and dry heat extremes may lead to inaccuracy in projecting crop yield responses to warming and changing humidity.