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Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

A variety of phase transitions have been found in two-dimensional layered materials, but some of their atomic-scale mechanisms are hard to clearly understand. Here, we report the discovery of a phase transition whose mechanism is identified as interlayer sliding in lead iodides, a layered material widely used to synthesize lead halide perovskites. The low-temperature crystal structure of lead iodides is found not 2H polytype as known before, but non-centrosymmetric 4H polytype. This undergoes the order-disorder phase transition characterized by the abrupt spectral broadening of valence bands, taken by angle-resolved photoemission, at the critical temperature of 120 K. It is accompanied by drastic changes in simultaneously taken photocurrent and photoluminescence. The transmission electron microscopy is used to reveal that lead iodide layers stacked in the form of 4H polytype at low temperatures irregularly slide over each other above 120 K, which can be explained by the low energy barrier of only 10.6 meV/atom estimated by first principles calculations. Our findings suggest that interlayer sliding is a key mechanism of the phase transitions in layered materials, which can significantly affect optoelectronic and optical characteristics.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5′-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNAGly(GCC) to produce 5′-tRHs (5′-tRH-GlyGCC) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. Levels of 5′-tRH-GlyGCC positively affect cancer cell proliferation and modulate mRNA isoform biogenesis both in vitro and in vivo; these effects require co-expression of two nuclear ribonucleoproteins, HNRNPM and HNRNPH2, which we identify as binding proteins of 5′-tRH-GlyGCC. In addition, under ER stress in vivo, we observe simultaneous induction of IRE1α and 5′-tRH-GlyGCC expression in mouse organs and a distantly related organism, Cryptococcus neoformans. Thus, collectively, our findings indicate an evolutionarily conserved function for IRE1α-generated 5′-tRH-GlyGCC in cellular adaptation upon ER stress. RNA fragments derived from cleaved transfer RNAs play roles in gene regulation and cell proliferation. Here, the authors report that upon ER stress, an ER ribonuclease produces a specific tRNA fragment that promotes cancer cell proliferation and modulates mRNA alternative splicing. [ABSTRACT FROM AUTHOR]