Sexual dimorphism in body clocks Anderson, Seán T; FitzGerald, Garret A
Science (American Association for the Advancement of Science),
09/2020, Letnik:
369, Številka:
6508
Journal Article
Cryptochromes are cardinal constituents of the circadian clock, which orchestrates daily physiological rhythms in living organisms. A growing body of evidence points to their participation in ...pathways that have not traditionally been associated with circadian clock regulation, implying that cryptochromes may be subject to modulation by multiple signaling mechanisms. In this study, we demonstrate that human CRY2 (hCRY2) forms a complex with the large, modular scaffolding protein known as Multi‐PDZ Domain Protein 1 (MUPP1). This interaction is facilitated by the calcium‐binding protein Calmodulin (CaM) in a calcium‐dependent manner. Our findings suggest a novel cooperative mechanism for the regulation of mammalian cryptochromes, mediated by calcium ions (Ca2+) and CaM. We propose that this Ca2+/CaM‐mediated signaling pathway may be an evolutionarily conserved mechanism that has been maintained from Drosophila to mammals, most likely in relation to its potential role in the broader context of cryptochrome function and regulation. Further, the understanding of cryptochrome interactions with other proteins and signaling pathways could lead to a better definition of its role within the intricate network of molecular interactions that govern circadian rhythms.
Circadian rhythms are archetypal examples of nonlinear oscillations. While these oscillations are usually attributed to circuits of biochemical interactions among clock genes and proteins, recent ...experimental studies reveal that they are also affected by the cell's mechanical environment. Here, we extend a standard biochemical model of circadian rhythmicity to include mechanical effects in a parametric manner. Using experimental observations to constrain the model, we suggest specific ways in which the mechanical signal might affect the clock. Additionally, a bifurcation analysis of the system predicts that these mechanical signals need to be within an optimal range for circadian oscillations to occur.
Heavy use of alcohol can lead to addictive behaviors and to eventual alcohol‐related tissue damage. While increased consumption of alcohol has been attributed to various factors including level of ...alcohol exposure and environmental factors such as stress, data from behavioral scientists and physiological researchers are revealing roles for the circadian rhythm in mediating the development of behaviors associated with alcohol use disorder as well as the tissue damage that drives physiological disease. In this work, we compile recent work on the complex mutually influential relationship that exists between the core circadian rhythm and the pharmacodynamics of alcohol. As we do so, we highlight implications of the relationship between alcohol and common circadian mechanisms of effected organs on alcohol consumption, metabolism, toxicity, and pathology.
Role of Core Circadian Clock in Alcohol‐Induced Pathology: Alcohol mediates disruption of circadian rhythm mechanism(s) inducing the increased intestinal permeability that is critical to the development and progression of alcoholic liver disease.
The circadian clock controls the expression of a large proportion of protein‐coding genes in mammals and can modulate a wide range of physiological processes. Recent studies have demonstrated that ...disruption or dysregulation of the circadian clock is involved in the development and progression of several diseases, including cancer. The cell cycle is considered to be the fundamental process related to cancer. Accumulating evidence suggests that the circadian clock can control the expression of a large number of genes related to the cell cycle. This article reviews the mechanism of cell cycle‐related genes whose chromatin regulatory elements are rhythmically occupied by core circadian clock transcription factors, while their RNAs are rhythmically expressed. This article further reviews the identified oscillatory cell cycle‐related genes in higher organisms such as baboons and humans. The potential functions of these identified genes in regulating cell cycle progression are also discussed. Understanding how the molecular clock controls the expression of cell cycle genes will be beneficial for combating and treating cancer.
The Urothelium: Life in a Liquid Environment Dalghi, Marianela G; Montalbetti, Nicolas; Carattino, Marcelo D ...
Physiological reviews,
10/2020, Letnik:
100, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high-resistance but adaptable barrier that surveils its mechanochemical environment and ...communicates changes to underlying tissues including afferent nerve fibers and the smooth muscle. The goal of this review is to summarize new insights into urothelial biology and function that have occurred in the past decade. After familiarizing the reader with key aspects of urothelial histology, we describe new insights into urothelial development and regeneration. This is followed by an extended discussion of urothelial barrier function, including information about the roles of the glycocalyx, ion and water transport, tight junctions, and the cellular and tissue shape changes and other adaptations that accompany expansion and contraction of the lower urinary tract. We also explore evidence that the urothelium can alter the water and solute composition of urine during normal physiology and in response to overdistension. We complete the review by providing an overview of our current knowledge about the urothelial environment, discussing the sensor and transducer functions of the urothelium, exploring the role of circadian rhythms in urothelial gene expression, and describing novel research tools that are likely to further advance our understanding of urothelial biology.
The circadian clock orchestrates a wide variety of physiological and behavioral processes, enabling animals to adapt to daily environmental changes, particularly the day-night cycle. However, the ...circadian clock's role in the developmental processes remains unclear. Here, we employ the in vivo long-term time-lapse imaging of retinotectal synapses in the optic tectum of larval zebrafish and reveal that synaptogenesis, a fundamental developmental process for neural circuit formation, exhibits circadian rhythm. This rhythmicity arises primarily from the synapse formation rather than elimination and requires the hypocretinergic neural system. Disruption of this synaptogenic rhythm, by impairing either the circadian clock or the hypocretinergic system, affects the arrangement of the retinotectal synapses on axon arbors and the refinement of the postsynaptic tectal neuron's receptive field. Thus, our findings demonstrate that the developmental synaptogenesis is under hypocretin-dependent circadian regulation, suggesting an important role of the circadian clock in neural development.
The circadian system in the human body responds to daily environmental changes to optimise behaviour according to the biological clock and also influences various physiological processes. The ...suprachiasmatic nuclei are located in the anterior hypothalamus of the brain, and they synchronise to the 24 h light/dark cycle. Human physiological functions are highly dependent on the regulation of the internal circadian clock. Skeletal muscles comprise the largest collection of peripheral clocks in the human body. Both central and peripheral clocks regulate the interaction between the musculoskeletal system and energy metabolism. The skeletal muscle circadian clock plays a vital role in lipid and glucose metabolism. The pathogenesis of osteoporosis is related to an alteration in the circadian rhythm. In the present review, we discuss the disturbance of the circadian rhythm and its resultant effect on the musculoskeletal system. We also discuss the nutritional strategies that are potentially effective in maintaining the system's homeostasis. Active collaborations between nutritionists and physiologists in the field of chronobiological and chrononutrition will further clarify these interactions. This review may be necessary for successful interventions in reducing morbidity and mortality resulting from musculoskeletal disturbances.
Wearable devices have been increasingly used in research to provide continuous physical activity monitoring, but how to effectively extract features remains challenging for researchers. To analyze ...the generated actigraphy data in large-scale population studies, we developed computationally efficient methods to derive sleep and activity features through a Hidden Markov Model-based sleep/wake identification algorithm, and circadian rhythm features through a Penalized Multi-band Learning approach adapted from machine learning. Unsupervised feature extraction is useful when labeled data are unavailable, especially in large-scale population studies. We applied these two methods to the UK Biobank wearable device data and used the derived sleep and circadian features as phenotypes in genome-wide association studies. We identified 53 genetic loci with p<5×10-8 including genes known to be associated with sleep disorders and circadian rhythms as well as novel loci associated with Body Mass Index, mental diseases and neurological disorders, which suggest shared genetic factors of sleep and circadian rhythms with physical and mental health. Further cross-tissue enrichment analysis highlights the important role of the central nervous system and the shared genetic architecture with metabolism-related traits and the metabolic system. Our study demonstrates the effectiveness of our unsupervised methods for wearable device data when additional training data cannot be easily acquired, and our study further expands the application of wearable devices in population studies and genetic studies to provide novel biological insights.
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