Large-language models facilitate discovery of the molecular signatures regulating sleep and activity.

Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.

Wolfram syndrome 1 regulates sleep in dopamine receptor neurons by modulating calcium homeostasis.

Sleep disruptions are quite common in psychological disorders, but the underlying mechanism remains obscure. Wolfram syndrome 1 (WS1) is an autosomal recessive disease mainly characterized by diabetes insipidus/mellitus, neurodegeneration and psychological disorders. It is caused by loss-of function mutations of the WOLFRAM SYNDROME 1 (WFS1) gene, which encodes an endoplasmic reticulum (ER)-resident transmembrane protein.

Phosphorylation Promotes the Accumulation of PERIOD Protein Foci.

Circadian clock drives the 24-h rhythm in our behavior and physiology. The molecular clock consists of a series of transcriptional/translational feedback loops operated by a number of clock genes. A very recent study reported that the clock protein PERIOD (PER) is organized into discrete foci at the nuclear envelope in fly circadian neurons, which is believed to be important for controlling the subcellular localization of clock genes.

Gut AstA mediates sleep deprivation-induced energy wasting in Drosophila.

Severe sleep deprivation (SD) has been highly associated with systemic energy wasting, such as lipid loss and glycogen depletion. Despite immune dysregulation and neurotoxicity observed in SD animals, whether and how the gut-secreted hormones participate in SD-induced disruption of energy homeostasis remains largely unknown. Using Drosophila as a conserved model organism, we characterize that production of intestinal Allatostatin A (AstA), a major gut-peptide hormone, is robustly increased in adult flies bearing severe SD.

Small-sample learning reveals propionylation in determining global protein homeostasis.

Proteostasis is fundamental for maintaining organismal health. However, the mechanisms underlying its dynamic regulation and how its disruptions lead to diseases are largely unclear. Here, we conduct in-depth propionylomic profiling in Drosophila, and develop a small-sample learning framework to prioritize the propionylation at lysine 17 of H2B (H2BK17pr) to be functionally important.

Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy.

Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study, three novel mutations in NPRL3 (nitrogen permease regulator-like 3), c.937_945del, c.

Developmental growth plate cartilage formation suppressed by artificial light at night via inhibiting BMAL1-driven collagen hydroxylation.

Exposure to artificial light at night (LAN) can induce obesity, depressive disorder and osteoporosis, but the pernicious effects of excessive LAN exposure on tissue structure are poorly understood. Here, we demonstrated that artificial LAN can impair developmental growth plate cartilage extracellular matrix (ECM) formation and cause endoplasmic reticulum (ER) dilation, which in turn compromises bone formation. Excessive LAN exposure induces downregulation of the core circadian clock protein BMAL1, which leads to collagen accumulation in the ER.

Proteome and Ubiquitylome Analyses of Maize Endoplasmic Reticulum under Heat Stress.

High temperatures severely affect plant growth and pose a threat to global crop production. Heat causes the accumulation of misfolded proteins in the endoplasmic reticulum(ER), as well as triggering the heat-shock response (HSR) in the cytosol and the unfolded protein response (UPR) in the ER. Excessive misfolded proteins undergo further degradation through ER-associated degradation (ERAD).

Time-restricted feeding is an intervention against excessive dark-phase sleepiness induced by obesogenic diet.

High-fat diet (HFD)-induced obesity is a growing epidemic and major health concern. While excessive daytime sleepiness (EDS) is a common symptom of HFD-induced obesity, preliminary findings suggest that reduced wakefulness could be improved with time-restricted feeding (TRF). At present, however, the underlying neural mechanisms remain largely unknown.

Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear.

Theaflavin-3,3'-Digallate from Black Tea Inhibits Neointima Formation Through Suppression of the PDGFRβ Pathway in Vascular Smooth Muscle Cells.

The abnormal neointima formation caused by the phenotypic switching of vascular smooth cells (VSMCs) into a synthetic state plays a key role in the pathogenesis of various vascular diseases, including atherosclerosis and postangioplasty restenosis. Theaflavin-3,3'-digallate (TF3) in black tea has been reported to exert antiinflammatory and anticancer effects, but its role in neointima formation remains unclear. Here, we delineated a remarkable effect of TF3 in suppressing neointima formation of VSMCs as well as the ability of primary rat aortic smooth cells (RASMCs) to proliferate and migrate .

β-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met.

The β-adrenergic receptor (βAR) is a G protein-coupled receptor (GPCR) that mediates the majority of cellular responses to external stimuli. Aberrant expression of βAR results in various pathophysiological disorders, including tumorigenesis, but little is known about its role in liver regeneration. This study aims to investigate the impact and the underlying mechanism of βAR in liver regeneration.

A Novel SPAST Mutation Results in Spastin Accumulation and Defects in Microtubule Dynamics.

Background: Haploinsufficiency is widely accepted as the pathogenic mechanism of spastic paraplegia type 4 (SPG4). However, there are some cases that cannot be explained by reduced function of the spastin protein encoded by SPAST.

Objectives: To identify the causative gene of autosomal dominant hereditary spastic paraplegia in three large Chinese families and explore the pathological mechanism of a spastin variant.

Protein arginine methyltransferase 7 modulates neuronal excitability by interacting with NaV1.9.

Human NaV1.9 (hNaV1.9), encoded by SCN11A, is preferentially expressed in nociceptors, and its mutations have been linked to pain disorders.

p.His16Arg of STXBP1 (MUNC18-1) Associated With Syntaxin 3B Causes Autosomal Dominant Congenital Nystagmus.

Congenital nystagmus (CN) is an ocular movement disorder manifested as involuntary conjugated binocular oscillation and usually occurs in early infancy. The pathological mechanism underlying CN is still poorly understood. We mapped a novel genetic locus 9q33.

Brain activity and transcriptional profiling in mice under chronic jet lag.

Shift work is known to be associated with an increased risk of neurological and psychiatric diseases, but how it contributes to the development of these diseases remains unclear. Chronic jet lag (CJL) induced by shifting light-dark cycles repeatedly is a commonly used protocol to mimic the environmental light/dark changes encountered by shift workers. Here we subjected wildtype mice to CJL and performed positron emission tomography imaging of glucose metabolism to monitor brain activities.

Germline Mutation of PLCD1 Contributes to Human Multiple Pilomatricomas through Protein Kinase D/Extracellular Signal-Regulated Kinase1/2 Cascade and TRPV6.

Pilomatricoma, a benign skin appendage tumor, also known as calcifying epithelioma, consists of islands of epithelial cells histologically that contain anucleated cells in the center surrounded by basophilic cells and partial calcification. Sporadic pilomatricomas commonly have somatic mutations in the gene CTNNB1, but causative genes from germline and the underlying pathophysiology are unclear. In this study, we identified a germline missense variant of PLCD1 encoding PLCδ1, c.