Mammalian circadian

The circadian clocks are cell-autonomous intrinsic oscillators existing throughout the body to coordinate intracellular and intercellular functions of each organ or tissue. The circadian clock oscillation gradually emerges during mid-to-late gestation in the mammalian developmental process. Recently, it has been revealed that the in vitro differentiation of mouse ES cells recapitulates the circadian clock development. Moreover, reprogramming of the cells results in the redisappearance of the clock, indicating that circadian clocks are tightly coupled with cellular differentiation...

Rhythmicity is a intrinsic feature of biological systems, including the hypothalamic-pituitary-adrenal axis, a mammalian neurohormonal system crucial both in daily life and as a network that responds to stressful stimuli. Circadian and ultradian rhythmicity underlie HPA activity in rodents and in humans, regulating gene expression, metabolism and behavior, and adverse consequences occur when rhythms are disturbed. In the assessment of human disease, the complexity of HPA rhythmicity is rarely acknowledged or understood, and is currently a limitation to better diagnosis and treatment...

Light is an environmental factor that is extrinsic to animals themselves and that exerts a profound influence on the regulation of circadian, neurohormonal, metabolic, and neurobehavioral systems of all animals, including research animals. These widespread biologic effects of light are mediated by distinct photoreceptors-rods and cones that comprise the conventional visual system and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) of the nonvisual system that interact with the rods and cones...

Sleep genetics is an intriguing, as yet less understood, understudied, emerging area of biological and medical discipline. A generalist may not be aware of the current status of the field given the variety of journals that have published studies on the genetics of sleep and the circadian clock over the years. For researchers venturing into this fascinating area, this review thus includes fundamental features of circadian rhythm and genetic variables impacting sleep-wake cycles. Sleep/wake pathway medication exposure and susceptibility are influenced by genetic variations, and the responsiveness of sleep-related medicines is influenced by several functional polymorphisms...

The light-sensitive protein Opsin 3 (Opn3) is present throughout the mammalian brain; however, the role of Opn3 in this organ remains unknown. Since Opn3 encoded mRNA is modulated in the supraoptic and paraventricular nucleus of the hypothalamus in response to osmotic stimuli, we have explored by in situ hybridization the expression of Opn3 in these nuclei. We have demonstrated that Opn3 is present in the male rat magnocellular neurones expressing either the arginine vasopressin or oxytocin neuropeptides and that Opn3 increases in both neuronal types in response to osmotic stimuli, suggesting that Opn3 functions in both cell types and that it might be involved in regulating water balance...

Rheumatoid arthritis (RA) is a multifaceted autoimmune disease characterized by systemic inflammation, affecting both articular and extra-articular structures. This condition results in inflammation of joints and synovial membranes, accompanied by the development of systemic comorbidities. Despite extensive research, the precise pathogenic mechanisms responsible for RA have yet to be completely understood. RNA methylation, a burgeoning epigenetic alteration, assumes a pivotal function in the regulation of a myriad of biological phenomena, encompassing immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division...

Liquid-liquid phase separation (LLPS) underlies diverse biological processes. Because most LLPS studies were performed in vitro using recombinant proteins or in cells that overexpress protein, the physiological relevance of LLPS for endogenous protein is often unclear. PERIOD, the intrinsically disordered domain-rich proteins, are central mammalian circadian clock components and interact with other clock proteins in the core circadian negative feedback loop. Different core clock proteins were previously shown to form large complexes...

Emerging evidence has highlighted that the gut microbiota plays a critical role in the regulation of various aspects of mammalian physiology and behavior, including circadian rhythms. Circadian rhythms are fundamental behavioral and physiological processes that are governed by circadian pacemakers in the brain. Since mice are nocturnal, voluntary wheel running activity mostly occurs at night. This nocturnal wheel-running activity is driven by the primary circadian pacemaker located in the suprachiasmatic nucleus (SCN)...

UNLABELLED: The molecular clock that generates daily rhythms of behavior and physiology consists of interlocked transcription-translation feedback loops. In Drosophila , the primary feedback loop involving the CLOCK-CYCLE transcriptional activators and the PERIOD-TIMELESS transcriptional repressors is interlocked with a secondary loop involving VRILLE (VRI) and PAR DOMAIN PROTEIN 1 (PDP1), a repressor and activator of Clock transcription, respectively. Whereas extensive studies have found numerous transcriptional, translational, and post-translational modulators of the primary loop, relatively little is known about the secondary loop...

Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity in female mice and food entrainment in male mice...

Visual system function depends upon the elaboration of precise connections between retinal ganglion cell (RGC) axons and their central targets in the brain. Though some progress has been made in defining the molecules that regulate RGC connectivity required for the assembly and function of image-forming circuitry, surprisingly little is known about factors required for intrinsically photosensitive RGCs (ipRGCs) to target a principal component of the nonimage-forming circuitry: the suprachiasmatic nucleus (SCN)...

The pineal gland has evolved from a photoreceptive organ in fish to a neuroendocrine organ in mammals. This study integrated multiple daytime single-cell RNA-seq datasets from the pineal glands of zebrafish, rats, and monkeys, providing a detailed examination of the evolutionary transition at single-cell resolution. We identified key factors responsible for the anatomical and functional transformation of the pineal gland. We retrieved and integrated daytime single-cell transcriptomic datasets from the pineal glands of zebrafish, rats, and monkeys, resulting in a total of 22 431 cells after rigorous quality filtering...

Temperature sensing is critical for the survival of living organisms.1 , 2 Thermosensitive transient receptor-potential (TRP) cation channels function as thermosensors in mammals.2 , 3 , 4 , 5 , 6 In contrast to animals, land plants lack TRP genes.7 , 8 , 9 Previous patch-clamp studies in plant cells suggested the presence of ion channels whose activities are related to temperature, implying the presence of TRP-like channels.10 , 11 , 12 , 13 , 14 However, the molecular entities of such temperature-sensitive ion channels were still unknown in land plants...

The incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. The lack of a safe and effective causal therapy in cognitive decline is an aggravating factor and requires investigations into the repurposing of commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new and efficient class of hypoglycemic drugs and, due to their pleiotropic effects, have indications that go beyond diabetes...

Circadian rhythms are internal 24-h intrinsic oscillations that are present in essentially all mammalian cells and can influence numerous biological processes. Cardiac function is known to exhibit a circadian rhythm and is strongly affected by the day/night cycle. Many cardiovascular variables, including heart rate, heart rate variability (HRV), electrocardiogram (ECG) waveforms, endothelial cell function, and blood pressure, demonstrate robust circadian rhythms. Many experiential and clinical studies have highlighted that disruptions in circadian rhythms can ultimately lead to maladaptive cardiac function...

Various mammalian cells have autonomous cellular clocks that are produced by the transcriptional cycle of clock genes. Cellular clocks provide circadian rhythms for cellular functions via transcriptional and cytoskeletal regulation. The vast majority of mammalian cells possess a primary cilium, an organelle protruding from the cell surface. Here, we investigated the little-known relationship between circadian rhythm and primary cilia. The length and number of primary cilia showed circadian dynamics both in vitro and in vivo...

Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures...

Liquid-liquid phase separation (LLPS) underlies diverse biological processes. Because most LLPS studies were performed in vitro or in cells that overexpress protein, the physiological relevance of LLPS is unclear. PERIOD proteins are central mammalian circadian clock components and interact with other clock proteins in the core circadian negative feedback loop. Different core clock proteins were previously shown to form large complexes. Here we show that when transgene was stably expressed, PER2 formed nuclear phosphorylation-dependent LLPS condensates that recruited other clock proteins...

The key circadian genes, Period1(Per1), Period2(Per2), and Period3(Per3), constitute the mammalian Period gene family. The abnormal expression of Per1 and Per2 is closely related to tumor development, but there are few reports on Per3 and tumorigenesis. This study was conducted to determine whether the abnormal expression of Per3 could influence the progression of astroblastoma. The results indicated that the expression level of Per3 was increased in astroblastoma cells, and the high expression of Per3 was correlated with the poor overall survival time of glioma patients...

Adaptation of physiology and behavior to seasonal changes in the environment are for many organisms essential for survival. Most of our knowledge about the underlying mechanisms comes from research on photoperiodic regulation of reproduction in plants, insects and mammals. However, even humans, who mostly live in environments with minimal seasonal influences, show annual rhythms in physiology (e.g., immune activity, brain function), behavior (e.g., sleep-wake cycles) and disease prevalence (e.g., infectious diseases)...