Showing papers in "Physiology in 2020"
TL;DR: This review highlights key mechanisms that have been proposed to contribute to COVID-19 progression from viral entry to multisystem organ failure, as well as the central role of the immune response in successful viral clearance or progression to death.
Abstract: The global epidemiology of coronavirus disease 2019 (COVID-19) suggests a wide spectrum of clinical severity, ranging from asymptomatic to fatal. Although the clinical and laboratory characteristics of COVID-19 patients have been well characterized, the pathophysiological mechanisms underlying disease severity and progression remain unclear. This review highlights key mechanisms that have been proposed to contribute to COVID-19 progression from viral entry to multisystem organ failure, as well as the central role of the immune response in successful viral clearance or progression to death.
170 citations
TL;DR: The DNA sensors Toll-like receptor 9 (TLR9), cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), absent in melanoma 2 (AIM2), and interferons gamma-inducible 16 (IFI16), their ligands, and their physiological significance are examined.
Abstract: The innate immune system recognizes conserved pathogen-associated molecular patterns and produces inflammatory cytokines that direct downstream immune responses. The inappropriate localization of DNA within the cell cytosol or endosomal compartments indicates that a cell may either be infected by a DNA virus or bacterium, or has problems with its own nuclear integrity. This DNA is sensed by certain receptors that mediate cytokine production and, in some cases, initiate an inflammatory and lytic form of cell death called pyroptosis. Dysregulation of these DNA-sensing pathways is thought to contribute to autoimmune diseases and the development of cancer. In this review, we will discuss the DNA sensors Toll-like receptor 9 (TLR9), cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), absent in melanoma 2 (AIM2), and interferon gamma-inducible 16 (IFI16), their ligands, and their physiological significance. We will also examine the less-well-understood DEAH- and DEAD-box helicases DHX9, DHX36, DDX41, and RNA polymerase III, each of which may play an important role in DNA-mediated innate immunity.
90 citations
TL;DR: This review focuses on the contribution that persistent inward currents mediated by voltage-gated Na+ and Ca2+ channels make to motoneuronal discharge and how the nonlinearities they engender impede the construction of a comprehensive model of motor control.
Abstract: All movements are generated by the activation of motoneurons, and hence their input-output properties define the final step in processing of all motor commands. A major challenge to understanding t...
77 citations
TL;DR: Melatonin reprograms glucose metabolism in cancer cells to a normal cell phenotype and serves as a necessary co-factor for the rate-limiting enzyme in melatonin synthesis, thus ensuring melatonin production in mitochondria of normal cells.
Abstract: In cancer cells, glucose is primarily metabolized to pyruvate and then to lactate in the cytosol. By allowing the conversion of pyruvate to acetyl-CoA in mitochondria, melatonin reprograms glucose metabolism in cancer cells to a normal cell phenotype. Acetyl-CoA in the mitochondria also serves as a necessary co-factor for the rate-limiting enzyme in melatonin synthesis, thus ensuring melatonin production in mitochondria of normal cells.
73 citations
TL;DR: It is suggested that the systems that control animal behavior evolved from ancient mechanisms adapting preexisting ionic and neurotransmitter mechanisms to regulate individual cell behaviors during morphogenesis.
Abstract: Nervous systems are traditionally thought of as providing sensing and behavioral coordination functions at the level of the whole organism. What is the evolutionary origin of the mechanisms enablin...
61 citations
TL;DR: The molecular basis of these diseases is explained based on current understanding of the transport mechanism of members of the mitochondrial carrier family (SLC25).
Abstract: Members of the mitochondrial carrier family (SLC25) transport a variety of compounds across the inner membrane of mitochondria. These transport steps provide building blocks for the cell and link the pathways of the mitochondrial matrix and cytosol. An increasing number of diseases and pathologies has been associated with their dysfunction. In this review, the molecular basis of these diseases is explained based on our current understanding of their transport mechanism.
60 citations
TL;DR: The current literature regarding sex differences in thermoregulation and recommendations for heat-illness risk-mitigation strategies are evaluated.
Abstract: The participation of women in physically strenuous athletic and occupational tasks has increased substantially in the past decade. Female sex steroids have influences on thermoregulatory processes ...
51 citations
TL;DR: The benefits experienced by individuals exposed to several weeks of treatment with electrical stimulation of muscle suggest that the underlying adaptations involve several physiological systems, but little is known about the specific changes elicited by such interventions.
Abstract: The generation of action potentials in intramuscular motor and sensory axons in response to an imposed external current source can evoke muscle contractions and elicit widespread responses througho...
45 citations
TL;DR: An overview of gut microbial metabolites documented thus far to play a role in blood pressure regulation is provided and includes short-chain fatty acids, which can signal via G-protein-coupled receptors, and trimethylamine-N oxide.
Abstract: Shifts in the gut microbiome play a key role in blood pressure regulation, and changes in the production of gut microbial metabolites are likely to be a key mechanism. Known gut microbial metabolites include short-chain fatty acids, which can signal via G-protein-coupled receptors, and trimethylamine-N oxide. In this review, we provide an overview of gut microbial metabolites documented thus far to play a role in blood pressure regulation.
44 citations
TL;DR: The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.
Abstract: Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system...
42 citations
TL;DR: New evidence demonstrates that calcium-dependent binding of N2A titin to actin increases titin stiffness in active skeletal muscles, which explains many long-standing enigmas of muscle physiology.
Abstract: Muscle has conventionally been viewed as a motor that converts chemical to kinetic energy in series with a passive spring, but new insights emerge when muscle is viewed as a composite material whose elastic elements are tuned by activation. New evidence demonstrates that calcium-dependent binding of N2A titin to actin increases titin stiffness in active skeletal muscles, which explains many long-standing enigmas of muscle physiology.
TL;DR: The role of the gut microbiota and its products for the pathogenesis and therapy of chronic liver diseases and cholestatic liver diseases is reviewed.
Abstract: The gut and the liver have a bidirectional communication via the biliary system and the portal vein. The intestinal microbiota and microbial products play an important role for modulating liver diseases such as alcohol-associated liver disease, non-alcoholic fatty liver disease and steatohepatitis, and cholestatic liver diseases. Here, we review the role of the gut microbiota and its products for the pathogenesis and therapy of chronic liver diseases.
TL;DR: This work will review and compare the outcomes and underlying mechanisms of IF in both animal and human studies, and the limitations of IF and inconsistencies between preclinical and clinical studies will be discussed to provide insight into the gaps between translating research from bench to bedside.
Abstract: Intermittent fasting (IF) is a widely practiced dietary method that encompasses periodic restriction of food consumption. Due to its protective benefits against metabolic diseases, aging, and cardiovascular and neurodegenerative diseases, IF continues to gain attention as a preventative and therapeutic intervention to counteract these chronic diseases. Although numerous animal studies have reported positive health benefits of IF, its feasibility and efficacy in clinical settings remain controversial. Importantly, since dietary interventions such as IF have systemic effects, thoroughly investigating the tissue-specific changes in animal models is crucial to identify IF's mechanism and evaluate its potential adverse effects in humans. As such, we will review and compare the outcomes and underlying mechanisms of IF in both animal and human studies. Moreover, the limitations of IF and inconsistencies between preclinical and clinical studies will be discussed to provide insight into the gaps between translating research from bench to bedside.
TL;DR: The roles of cellular polyamines in maintaining the integrity of the gut epithelium are highlighted, focusing on the emerging evidence of polyamine in the regulation of gut epithelial renewal and barrier function.
Abstract: Polyamines regulate a variety of physiological functions and are involved in pathogenesis of diverse human diseases. The epithelium of the mammalian gut mucosa is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through well-controlled mechanisms. Here, we highlight the roles of cellular polyamines in maintaining the integrity of the gut epithelium, focusing on the emerging evidence of polyamines in the regulation of gut epithelial renewal and barrier function. Gut mucosal growth depends on the available supply of polyamines to the dividing cells in the crypts, and polyamines are also essential for normal gut epithelial barrier function. Polyamines modulate expression of various genes encoding growth-associated proteins and intercellular junctions via distinct mechanisms involving RNA-binding proteins and noncoding RNAs. With the rapid advance of polyamine biology, polyamine metabolism and transport are promising therapeutic targets in our efforts to protect the gut epithelium and barrier function in patients with critical illnesses.
TL;DR: An overview of recent concepts and results on the mechanisms of sleep-related memory consolidation is provided and the latest studies strongly impacting future directions of research in this field are highlighted.
Abstract: Sleep can benefit memory consolidation. The characterization of brain regions underlying memory consolidation during sleep, as well as their temporal interplay, reflected by specific patterns of br...
TL;DR: To be impactful, future breast biomechanics research needs to fill gaps in knowledge, particularly related to breast composition and density, and to improve methods to accurately measure the complexities of three-dimensional breast motion.
Abstract: Although half the world's population will develop breasts, there is limited research documenting breast structure or motion. Understanding breast structure and motion, however, is imperative for numerous applications, such as breast reconstruction, breast modeling to better diagnose and treat breast pathologies, and designing effective sports bras. To be impactful, future breast biomechanics research needs to fill gaps in our knowledge, particularly related to breast composition and density, and to improve methods to accurately measure the complexities of three-dimensional breast motion. These methods should then be used to investigate breast biomechanics while individuals, who represent the full spectrum of women in the population, participate in a broad range of activities of daily living and recreation.
TL;DR: This review highlights intrinsic and extrinsic modulators contributing to the remodeling process of pulmonary vascular remodeling.
Abstract: Exposure to hypoxia increases pulmonary vascular resistance, leading to elevated pulmonary arterial pressure and, potentially, right heart failure. Vascular remodeling is an important contributor to the increased pulmonary vascular resistance. Hyperproliferation of smooth muscle, endothelial cells, and fibroblasts, and deposition of extracellular matrix lead to increased wall thickness, extension of muscle into normally non-muscular arterioles, and vascular stiffening. This review highlights intrinsic and extrinsic modulators contributing to the remodeling process.
TL;DR: Pedomorphy, maintenance of juvenile traits throughout life, is most pronounced in extraordinarily long-lived naked mole-rats, and the nature of these intrinsic pedomorphic features may also contribute to their prolonged youthfulness, longevity, and healthspan.
Abstract: Pedomorphy, maintenance of juvenile traits throughout life, is most pronounced in extraordinarily long-lived naked mole-rats. Many of these traits (e.g., slow growth rates, low hormone levels, and delayed sexual maturity) are shared with spontaneously mutated, long-lived dwarf mice. Although some youthful traits likely evolved as adaptations to subterranean habitats (e.g., thermolability), the nature of these intrinsic pedomorphic features may also contribute to their prolonged youthfulness, longevity, and healthspan.
TL;DR: Ovarian hormones are associated with risk for binge eating in women and food-related reward processing may be one set of neurobiological factors that contribute to these relationships.
Abstract: Ovarian hormones are associated with risk for binge eating in women. Recent animal and human studies suggest that food-related reward processing may be one set of neurobiological factors that contr...
TL;DR: Opioids depress minute ventilation primarily by reducing respiratory rate, which results from direct effects on the preBötzinger Complex as well as from depression of the Parabrachial/Kölliker-Fuse Complex.
Abstract: Opioids depress minute ventilation primarily by reducing respiratory rate. This results from direct effects on the preBotzinger Complex as well as from depression of the Parabrachial/Kolliker-Fuse Complex, which provides excitatory drive to preBotzinger Complex neurons mediating respiratory phase-switch. Opioids also depress awake drive from the forebrain and chemodrive.
TL;DR: Characteristic breath-holds, obstructive sleep apnea, and aerophagia result in intermittent hypoxia, which, combined with mitochondrial dysfunction, causes oxidative stress-an important driver of the clinical presentation of RTT.
Abstract: Rett syndrome (RTT), an X-chromosome-linked neurological disorder, is characterized by serious pathophysiology, including breathing and feeding dysfunctions, and alteration of cardiorespiratory coupling, a consequence of multiple interrelated disturbances in the genetic and homeostatic regulation of central and peripheral neuronal networks, redox state, and control of inflammation. Characteristic breath-holds, obstructive sleep apnea, and aerophagia result in intermittent hypoxia, which, combined with mitochondrial dysfunction, causes oxidative stress-an important driver of the clinical presentation of RTT.
TL;DR: The pathogenicity of E. histolytica is reviewed and the latest knowledge on immune response and immune evasion mechanisms during amoebiasis are summarized.
Abstract: Entamoeba histolytica is a protozoan parasite responsible for amoebiasis, a disease with a high prevalence in developing countries. Establishing an amoebic infection involves interplay between pathogenic factors for invasion and tissue damage, and immune responses for protecting the host. Here, we review the pathogenicity of E. histolytica and summarize the latest knowledge on immune response and immune evasion mechanisms during amoebiasis.
TL;DR: This review highlights similarities and differences in sperm strategies, with examples within internal and external fertilizers, pointing out unresolved issues.
Abstract: Species preservation depends on the success of fertilization. Sperm are uniquely equipped to fulfill this task, and, although several mechanisms are conserved among species, striking functional dif...
TL;DR: In this article, a single conserved cysteine within the β-subunit (βCys93) of hemoglobin (Hb) was found to be the primary site of Hb S-nitrosylation.
Abstract: The supply of oxygen to tissues is controlled by microcirculatory blood flow. One of the more surprising discoveries in cardiovascular physiology is the critical dependence of microcirculatory blood flow on a single conserved cysteine within the β-subunit (βCys93) of hemoglobin (Hb). βCys93 is the primary site of Hb S-nitrosylation [i.e., S-nitrosothiol (SNO) formation to produce S-nitrosohemoglobin (SNO-Hb)]. Notably, S-nitrosylation of βCys93 by NO is favored in the oxygenated conformation of Hb, and deoxygenated Hb releases SNO from βCys93. Since SNOs are vasodilatory, this mechanism provides a physiological basis for how tissue hypoxia increases microcirculatory blood flow (hypoxic autoregulation of blood flow). Mice expressing βCys93A mutant Hb (C93A) have been applied to understand the role of βCys93, and RBCs more generally, in cardiovascular physiology. Notably, C93A mice are unable to effect hypoxic autoregulation of blood flow and exhibit widespread tissue hypoxia. Moreover, reactive hyperemia (augmentation of blood flow following transient ischemia) is markedly impaired. C93A mice display multiple compensations to preserve RBC vasodilation and overcome tissue hypoxia, including shifting SNOs to other thiols on adult and fetal Hbs and elsewhere in RBCs, and growing new blood vessels. However, compensatory vasodilation in C93A mice is uncoupled from hypoxic control, both peripherally (e.g., predisposing to ischemic injury) and centrally (e.g., impairing hypoxic drive to breathe). Altogether, physiological studies utilizing C93A mice are confirming the allosterically controlled role of SNO-Hb in microvascular blood flow, uncovering essential roles for RBC-mediated vasodilation in cardiovascular physiology and revealing new roles for RBCs in cardiovascular disease.
TL;DR: A better understanding of the mechanisms underlying the activation of bronchopulmonary C-fiber terminals may lead to novel therapeutics that would work in an additive or synergic manner with existing anti-inflammatory strategies.
Abstract: Stimulation of bronchopulmonary vagal afferent C fibers by inflammatory mediators can lead to coughing, chest tightness, and changes in breathing pattern, as well as reflex bronchoconstriction and ...
TL;DR: Early human life that starts at the onset of fertilization and ends with implantation of the embryo in the uterine wall is the foundation for a successful pregnancy and the different stages during this period require biomechanical mechanisms that are mostly unknown.
Abstract: Early human life that starts at the onset of fertilization and ends with implantation of the embryo in the uterine wall is the foundation for a successful pregnancy. The different stages during this period require biomechanical mechanisms, which are mostly unknown due to difficulties to conduct in vivo studies in humans.
TL;DR: This review speculates that destabilizing selection on parental care, and especially embryo incubation, drove the convergent evolution of many tetrapod traits, including endothermy.
Abstract: Parental care has evolved convergently an extraordinary number of times among tetrapods that reproduce terrestrially, suggesting strong positive selection for this behavior in the terrestrial envir...
TL;DR: If metformin and statins will be used to prolong healthspan, they must understand their effects in those free of disease and in combination with exercise.
Abstract: There is an increased focus on treatments to extend the healthspan. There is solid evidence that exercise extends the healthspan, but other treatments, such as metformin and statins, are also gaini...
TL;DR: Air pollutants pose a serious worldwide health hazard, causing respiratory and cardiovascular morbidity and mortality, and a better understanding of the mechanisms involved would likely improve the management and treatment of pollution-related disease.
Abstract: Air pollutants pose a serious worldwide health hazard, causing respiratory and cardiovascular morbidity and mortality. Pollutants perturb the autonomic nervous system, whose function is critical to cardiopulmonary homeostasis. Recent studies suggest that pollutants can stimulate defensive sensory nerves within the cardiopulmonary system, thus providing a possible mechanism for pollutant-induced autonomic dysfunction. A better understanding of the mechanisms involved would likely improve the management and treatment of pollution-related disease.
TL;DR: The Na+-K+-Cl- cotransporters play key physiological and pathophysiological roles by regulating the membrane potential of many cell types and the movement of fluid across a variety of epithelial or endothelial structures.
Abstract: The Na+-K+-Cl- cotransporters play key physiological and pathophysiological roles by regulating the membrane potential of many cell types and the movement of fluid across a variety of epithelial or endothelial structures. As such, they should soon become invaluable targets for the treatment of various disorders including pain, epilepsy, brain edema, and hypertension. This review highlights the nature of these roles, the mechanisms at play, and the unresolved issues in the field.