Comprehensive Physiology

The human sensorimotor control system has exceptional abilities to perform skillful actions. We easily switch between strenuous tasks that involve brute force, such as lifting a heavy sewing machine, and delicate movements such as threading a needle in the same machine. Using a structure with different control architectures, the motor system is capable of updating its ability to perform through our daily interaction with the fluctuating environment. However, there are issues that make this a difficult computational problem for the brain to solve...

According to the Centers for Disease Control and Prevention, 1 in 2 U.S. adults have hypertension, and more than 1 in 7 chronic kidney disease. In fact, hypertension is the second leading cause of kidney failure in the United States; it is a complex disease characterized by, leading to, and caused by renal dysfunction. It is well-established that hypertensive renal damage is accompanied by mitochondrial damage and oxidative stress, which are differentially regulated and manifested along the nephron due to the diverse structure and functions of renal cells...

Type 2 diabetes (T2D) affects more than 32.3 million individuals in the United States, creating an economic burden of nearly $966 billion in 2021. T2D results from a combination of insulin resistance and inadequate insulin secretion from the pancreatic β cell. However, genetic and physiologic data indicate that defects in β cell function are the chief determinant of whether an individual with insulin resistance will progress to a diagnosis of T2D. The subcellular organelles of the insulin secretory pathway, including the endoplasmic reticulum, Golgi apparatus, and secretory granules, play a critical role in maintaining the heavy biosynthetic burden of insulin production, processing, and secretion...

Electrical mechanosensing is a process mediated by specialized ion channels, gated directly or indirectly by mechanical forces, which allows cells to detect and subsequently respond to mechanical stimuli. The activation of mechanosensitive (MS) ion channels, intrinsically gated by mechanical forces, or mechanoresponsive (MR) ion channels, indirectly gated by mechanical forces, results in electrical signaling across lipid bilayers, such as the plasma membrane. While the functions of mechanically gated channels within a sensory context (e...

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways...

Red blood cell (RBC) trapping describes the accumulation of RBCs in the microvasculature of the kidney outer medulla that occurs following ischemic acute kidney injury (AKI). Despite its prominence in human kidneys following AKI, as well as evidence from experimental models demonstrating that the severity of RBC trapping is directly correlated with renal recovery, to date, RBC trapping has not been a primary focus in understanding the pathogenesis of ischemic kidney injury. New evidence from rodent models suggests that RBC trapping is responsible for much of the tubular injury occurring in the initial hours after kidney reperfusion from ischemia...

Purine nucleotides play central roles in energy metabolism in the heart. Most fundamentally, the free energy of hydrolysis of the adenine nucleotide adenosine triphosphate (ATP) provides the thermodynamic driving force for numerous cellular processes including the actin-myosin crossbridge cycle. Perturbations to ATP supply and/or demand in the myocardium lead to changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage, potentially affecting myocardial energetics and, consequently, myocardial mechanics...

Insulin regulates energy metabolism involving multiple organ systems. Insulin resistance (IR) occurs when organs exhibit reduced insulin sensitivity, leading to difficulties in maintaining glucose homeostasis. IR ensures decades prior to development of overt diabetes and can cause silent metabolic derangements. IR is typically seen very early in the course of chronic kidney disease (CKD) and is evident even when the estimated glomerular filtration rate (eGFR) is within the normal range and IR persists at various stages of kidney disease...

The incidence of hypertensive disorders of pregnancy is increasing, which may be due to several factors, including an increased age at pregnancy and more comorbid health conditions during reproductive years. Preeclampsia, the most severe hypertensive disorder of pregnancy, has been associated with an increased risk of future disease, including cardiovascular and kidney diseases. Cellular senescence, the process of cell cycle arrest in response to many physiologic and maladaptive stimuli, may play an important role in the pathogenesis of preeclampsia and provide a mechanistic link to future disease...

Exercise capacity of an individual describes the ability to perform physical activity. This exercise capacity is influenced by intrinsic factors such as genetic constitution and extrinsic factors such as exercise training. On the metabolic level exercise and metabolism are linked. As an important site of metabolism and the main source for ATP needed for muscle contraction, mitochondrial function can determine exercise capacity, and exercise inversely influences mitochondrial function. It has been suggested that exercise mediates many of its effects due to such metabolic changes...

The lung is an inherently mechanosensitive organ, where cells of the airway and parenchyma experience a range of mechanical forces throughout life including shear, stretch, and compression, in both health and disease. In this regard, pediatric and adult lung diseases such as wheezing and asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) all involve macroscopic and cellular changes to the mechanical properties of the bronchial airways and/or parenchyma to varying extents...

No abstract text is available yet for this article.

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV biogenesis, cargo selection, recipient cell effects, and key considerations in isolation and characterization techniques. Studies on the physiological role of EVs have relied on cell-based model systems due to technical limitations of studying endogenous nanoparticles in vivo ...

Over the past two decades, with the advent and adoption of highly active anti-retroviral therapy, HIV-1 infection, a once fatal and acute illness, has transformed into a chronic disease with people living with HIV (PWH) experiencing increased rates of cardio-pulmonary vascular diseases including life-threatening pulmonary hypertension. Moreover, the chronic consequences of tobacco, alcohol, and drug use are increasingly seen in older PWH. Drug use, specifically, can have pathologic effects on the cardiovascular health of these individuals...

Microbiomes include bacteria, viruses, fungi, and other microbes. The microbiome modulates numerous aspects of host physiology and is critical in the pathophysiology of diseases, including colon cancer. Although gut bacterial pathogenesis has become an emerging area in colon cancer, the multi-kingdom aspect of microbiome has yet to be explored. Similar to the bacterial component of the microbiome, the virome contains certain makeup that varies between individuals. In the current review, we introduce the concepts of microbiome and microbiota, research history, methods for modern microbiome studies, and recent progress of mechanisms responsible for microbiome and virome in colon cancer...

In the gastrointestinal (GI) system, like in other organ systems, the histological structure is a key determinant of physiological function. Tissues form multiple layers in the GI tract to perform their specialized functions in secretion, absorption, and motility. Even at the single layer, the heterogeneous cell population performs a diverse range of digestive or regulatory functions. Although many details of such functions at the histological and cell biological levels were revealed by traditional methods such as cell sorting, isolation, and culture, as well as histological methods such as immunostaining and RNA in situ hybridization, recent advances in spatial single-cell technologies could further contribute to our understanding of the molecular makeup of GI histological structures by providing a genome-wide overview of how different genes are expressed across individual cells and tissue layers...

Heart transplantation (HT) is one of the prodigious achievements in modern medicine and remains the cornerstone in the treatment of patients with advanced heart failure. Advances in surgical techniques, immunosuppression, organ preservation, infection control, and allograft surveillance have improved short- and long-term outcomes thereby contributing to greater clinical success of HT. However, prolonged allograft and patient survival following HT are still largely restricted by the development of late complications, including allograft rejection, infection, cardiac allograft vasculopathy (CAV), and malignancy...

Inflammatory bowel disease (IBD) is an idiopathic disease of disordered chronic inflammation in the intestines that affects many people across the world. While the disease is still being better characterized, greater progress has been made in understanding the many components that intersect in the disease. Among these components are the many pieces that compose the intestinal epithelial barrier, the various cytokines and immune cells, and the population of microbes that reside in the intestinal lumen. Since their discovery, the hypoxia-inducible factors (HIFs) have been found to play an expansive role in physiology as well as diseases such as inflammation due to their role in oxygen sensing-related gene transcription, and metabolic control...

The incidence of obesity, insulin resistance, and type II diabetes (T2DM) continues to rise worldwide. The liver is a central insulin-responsive metabolic organ that governs whole-body metabolic homeostasis. Therefore, defining the mechanisms underlying insulin action in the liver is essential to our understanding of the pathogenesis of insulin resistance. During periods of fasting, the liver catabolizes fatty acids and stored glycogen to meet the metabolic demands of the body. In postprandial conditions, insulin signals to the liver to store excess nutrients into triglycerides, cholesterol, and glycogen...

The vestibular apparatus is highly specialized for detecting linear and angular acceleration, contributing importantly to perception of our position in the gravitational field and to motion in the three spatial axes. Beginning in the inner ear, spatial information is relayed toward higher cortical regions for processing, though the specific locations at which this action takes place remain somewhat ambiguous. This article aims to highlight brain regions known to be involved in the processing of spatial information, as well as those that contribute to a less widely documented function of the vestibular system-its capacity to regulate blood pressure via vestibulosympathetic reflexes...