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Diabetes is characterized by variable loss of insulin-producing beta cells, and new regenerative approaches to increasing the functional beta cell mass of patients hold promise for reversing disease progression. In this Review, we summarize recent chemical biology breakthroughs advancing our knowledge of beta cell regeneration. We present current chemical-based tools, sensors and mechanistic insig
Regeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of β-cell loss. Using lineage tra
Getting mature and functional stem cell-derived, insulin-producing β cells is an important step for disease modeling, drug screening, and cell replacement therapy. In this issue, Hua et al.1 used single-cell multiomics analysis coupled with chemical screening to identify a crucial role for ceramides in generating mature stem cell-derived β cells.
Insulin binds the insulin receptor (IR) and regulates anabolic processes in target tissues. Impaired IR signalling is associated with multiple diseases, including diabetes, cancer and neurodegenerative disorders. IRs have been reported to form nanoclusters at the cell membrane in several cell types, even in the absence of insulin binding. Here we exploit the nanoscale spatial organization of the I
Building a blastema from the stump is a key step of salamander limb regeneration. Stump-derived cells temporarily suspend their identity as they contribute to the blastema by a process generally referred to as dedifferentiation. Here, we provide evidence for a mechanism that involves an active inhibition of protein synthesis during blastema formation and growth. Relieving this inhibition results i
INTRODUCTION: Inconsistent results have been reported on the association between folic acid use in pregnancy and risk of GDM. The aim of this study was to estimate the association between folic acid use and GDM in two population-based Nordic cohorts.MATERIAL AND METHODS: Two cohort studies were conducted using data from the national population registers in Norway (2005-2018, n = 791,709) and Swede
Regenerating pancreatic β-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of β-cell regeneration, but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetic
BACKGROUND: Experimental animal studies suggest a novel role for the folate receptor 1 in β-cell differentiation in the pancreas, with potential implications for glycemic control. We tested the hypothesis of a protective association between prenatal folic acid use and neonatal diabetes or hyperglycemia and type 1 diabetes in an observational cohort study using data from the national population hea
Diabetes can be caused by an insufficiency in β-cell mass. Here, we performed a genetic screen in a zebrafish model of β-cell loss to identify pathways promoting β-cell regeneration. We found that both folate receptor 1 (folr1) overexpression and treatment with folinic acid, stimulated β-cell differentiation in zebrafish. Treatment with folinic acid also stimulated β-cell differentiation in cultur
There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole-genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β-cell regeneration. We then tested the proteins' ability to potentiate β-cell regeneration in zebrafish at supraphysiol
Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1,
Doctoral education is a critical mission of higher education institutions (HEIs), and supervisors of PhD students have a prominent role in the process. The relevance of their role in a successful PhD experience and outcome raises an important question: how are PhD supervisors trained for their roles in the doctoral education process? In this work, we aimed to identify the formal training component
Occupational balance is associated with better quality of life and recovery in mental health service users; however, research focusing on such relationships among older adults within this group remains scarce. This explorative cross-sectional study examined relationships between occupational balance and quality of life and recovery in 49 older mental health service users, while also investigating
γ-Tubulin (TUBG) is best known for organizing microtubules at centrosomes, but our work points to broader roles in chromatin and mitochondria. Our Communications Biology study extends this picture to centromeres and micronuclei—two unexpected contexts for TUBG.
This research conducted two vignette-based experiments designed to examine the potential role of social norms to motivate engagement with car sharing service (CSS) adoption in Spain. The analysis answered two research questions: a) to what extent do descriptive and injunctive social norms promote the willingness to adopt CSS, and b) what is the influence of injunctive norms on the willingness to u
A longstanding but untested hypothesis proposes that reduced bee visitation in tropical montane cloud forests has repeatedly driven the evolution of hummingbird pollination. Here, we test whether recently diverged bee and hummingbird pollination syndromes in two sister species are adapted to their pollination environments, and whether this reflects declining bee activity at higher elevations. Alte
Circular economy (CE) behaviors, such as reuse, repair, and sharing, are crucial to sustainable consumption; however, how and when such behaviors influence product users or consumers' personal well being remain underexplored. Specifically, limited insights exist regarding how engagement may foster feelings of enjoyment, a sense of mastery, or social belonging, as well as the contextual conditions
The fossil record offers a unique window into patterns of extinction and biodiversity recovery over deep time, and recent advances in analytical methods have significantly enhanced this research field. Our analysis of an updated dataset that includes 50 terminal taxa and 175 fossil occurrences of Ophiacodontidae, Edaphosauridae, and Sphenacodontidae (OES grade hereafter) using a recent implementat
Immunotherapy has reshaped melanoma treatment, yet the majority of patients fail to respond or develop resistance. Nerve growth factor receptor (NGFR/p75NTR/CD271) has been linked to melanoma aggressiveness and therapeutic resistance, but the underlying mechanisms remain unclear. Here, we demonstrate that pharmacologic inhibition of NGFR with THX-B significantly reduces distant metastasis and rest
