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e behaviors are still unclear. Using model-based neuroimaging approaches, we clarify that people integrate personal costs and non-linearly transformed other's benefits during altruistic decision-making and the implementations of the integration processes are supported by an extended common currency neural network. Importantly, multivariate analyses reveal that both empathy-related and cognitive control-related brain regions are involved in modulating individual variations of altruistic preference, which implicate complex psychological and computational processes. Our results provide a neurocomputational account of how people weigh between different attributes to make altruistic decisions and why altruistic preference varies to a great extent across individuals.Conceptions of genetic kinship have recently emerged as a powerful new discourse through which to trace and imagine connections between individuals and communities around the globe. This article argues that, as a new way to think and represent such connections, genetic discourses of relatedness constitute a new poetics of kinship. Discussing two exemplary contemporary novels, Amitav Ghosh's The Calcutta Chromosome (1995) and Zadie Smith's White Teeth (2000), this article argues further that literary fiction, and postcolonial literary fiction in particular, is uniquely positioned to critically engage this new biomedical discourse of global and interpersonal relations. Ghosh's and Smith's novels illuminate and amplify the concept of a cultural poetics of genetic kinship by aesthetically transcending the limits of genetic science to construct additional genetic connections between the West and the Global South on the level of metaphor and analogy. As both novels oscillate spatially between the West and a postcolonial Indian subcontinent, the texts' representations of literal and figurative genetic relations become a vehicle through which the novels test and reconfigure postcolonial and diasporic identities, as well as confront Western genetic science with alternative forms of knowledge. The emerging genetic imaginary highlights-evoking recent sociological and anthropological work-that meaningful kinship relations rely on biological as much as on cultural discourses and interpretations, especially in postcolonial and migrant contexts where genetic markers become charged with conflicting notions of connection and otherness.New-onset refractory status epilepticus and its subcategory febrile infection-related epilepsy syndrome are rare devastating clinical presentations in those without pre-existing relevant history, often in schoolchildren or young adults, without a clear cause on initial investigations. A cause is later identified in up to half of adults, but in many fewer children. Patients often require protracted intensive care and are at significant risk of dying. Functional disability is common and subsequent chronic epilepsy is the norm, but some people do have good outcomes, even after prolonged status epilepticus. Patients need prompt investigations and treatment. Anaesthetic and antiseizure medications are supplemented by other treatment modalities, including the ketogenic diet. Despite limited evidence, it is appropriate to try to modify the presumed underlying pathogenesis with immune modulation early, with a more recent focus on using interleukin inhibitors. Optimising management will require concerted multicentre international efforts.Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, the controllable replacement of one or two fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe a general strategy for sequential carbon-fluorine (C-F) bond functionalizations of trifluoroacetamides and trifluoroacetates. The reaction begins with the activation of a carbonyl oxygen atom by a 4-dimethylaminopyridine-boryl radical, followed by a spin-center shift to trigger the C-F bond scission. https://www.selleckchem.com/products/epz-5676.html A chemoselectivity-controllable two-stage process enables sequential generation of difluoro- and monofluoroalkyl radicals, which are selectively functionalized with different radical traps to afford diverse fluorinated products. The reaction mechanism and the origin of chemoselectivity were established by experimental and computational approaches.The aging of pancreatic β-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging β-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to β-cell failure. In this study, we defined the β-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from mouse and human senescent β-cells and a chemically induced mouse model of DNA damage capable of inducing SASP. These experiments revealed that the β-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species. Multiple SASP factors were transcriptionally upregulated in models of β-cell senescence, aging, insulin resistance, and T2D. Single-cell transcriptomic analysis of islets from an in vivo mouse model of reversible insulin resistance indicated unique and partly reversible changes in β-cell subpopulations associated with senescence. Collectively, these results demonstrate the unique secretory profile of senescent β-cells and its potential implication in health and disease.Diabetic retinopathy (DR) is the leading cause of acquired blindness in middle-aged people. The complex pathology of DR is difficult to dissect, given the convoluted cytoarchitecture of the retina. Here, we performed single-cell RNA sequencing (scRNA-seq) of retina from a model of type 2 diabetes, induced in leptin receptor-deficient (db/db) and control db/m mice, with the aim of elucidating the factors mediating the pathogenesis of DR. We identified 11 cell types and determined cell-type-specific expression of DR-associated loci via genome-wide association study (GWAS)-based enrichment analysis. DR also impacted cell-type-specific genes and altered cell-cell communication. Based on the scRNA-seq results, retinaldehyde-binding protein 1 (RLBP1) was investigated as a promising therapeutic target for DR. Retinal RLBP1 expression was decreased in diabetes, and its overexpression in Müller glia mitigated DR-associated neurovascular degeneration. These data provide a detailed analysis of the retina under diabetic and normal conditions, revealing new insights into pathogenic factors that may be targeted to treat DR and related dysfunctions.
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