Physiology

No abstract text is available yet for this article.

Beyond their role as brain immune cells, microglia act as metabolic sensors in response to changes in nutrient availability, thus playing a role in energy homeostasis. This review will highlight the evidence and challenges of studying the role of microglia in metabolism regulation.

The Nedd4 family of E3 ubiquitin ligases, consisting of a C2-WW(n)-HECT domain architecture, include the closely related Nedd4/Nedd4-1 and Nedd4L/Nedd4-2, which play critical roles in human physiology and pathophysiology. This review focuses on the regulation of enzymatic activity of these Nedd4 proteins, as well as on their roles in regulating stability and function of membrane and other signaling proteins, such as ion channels, ion transporters and growth factor receptors. The diseases caused by impairment of such regulation are discussed, as well as opportunities and challenges for targeting these enzymes for therapy...

No abstract text is available yet for this article.

Acute kidney frailty is a premorbid condition of diminished renal functional reserve that predisposes to acute kidney injury; this condition results from subclinical wear or distortion of renal homeostatic responses that protect the renal excretory function. Knowledge of its pathophysiological basis is critical for the development of diagnostic and therapeutic strategies that allow for prophylactic intervention and disease prevention.

Most explanations for the relationship between body size and metabolism invoke physical constraints; such explanations are evolutionarily inert, limiting their predictive capacity. Contemporary approaches to metabolic rate and life history lack the pluralism of foundational work. Here, we call for reforging of the lost links between optimization approaches and physiology.

The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters...

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide that poses a significant threat to human health. Cardiovascular disease (CVD) is the leading cause of mortality in NAFLD patients. NAFLD and CVD share risk factors such as obesity, insulin resistance, and type 2 diabetes. However, whether NAFLD is a causal risk factor for CVD remains a matter of debate. This review summarizes the evidence from prospective clinical and Mendelian randomization studies that underscore the potential causal relationship between NAFLD and CVD...

One of the biggest environmental alterations we have made to our species is the change in the exposure to light. During the day we typically sit behind glass windows illuminated by artificial light that is >400 times dimmer and has a very different spectrum than natural daylight. On the opposite end are the nights that are now lit up by several orders of magnitude. This review aims to provide food for thought as to why this matters for humans and other animals. Evidence from behavioral neuroscience, physiology, chronobiology and molecular biology is increasingly converging on the conclusions that the biological non-visual functions of light and photosensory molecules are highly complex...

The review deals with the release of endothelium-derived dopamine and 6-nitrodopamine (6-ND) and its effects on isolated vascular tissues and isolated heart. Human isolated umbilical cord vessels, human popliteal vessels, non-human primate vessels, and reptilia aortae, present basal release of both dopamine and 6-ND. The 6-ND basal release was significantly reduced when the tissues were treated with L-NAME and virtually abolished when the endothelium was mechanically removed. 6-Nitrodopamine is a potent vasodilator, and the mechanism of action responsible for this effect is the antagonism on dopamine D2 -like receptor...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

The sea urchin larva has been used by biologists for more than a century to study the development and evolution of animals. Surprisingly, very little information has been generated regarding the physiology of this small planktonic organism. However, in the context of anthropogenic CO2 -driven ocean acidification (OA), the membrane transport physiology and energetics of this marine model organism have received considerable attention in the past decade. This has led to the discovery of new, exciting physiological systems, including a highly alkaline digestive tract and the calcifying primary mesenchyme cells that generate the larval skeleton...

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure and a significant public health concern for which limited effective therapies exist. Inflammation triggered by comorbidity burden is a critical element of HFpEF pathophysiology. Here, we discuss evidence for comorbidity-driven systemic and myocardial inflammation and the mechanistic role of inflammation in pathological myocardial remodeling in HFpEF.

This issue of Physiology features four excellent review articles that highlight current research and discuss untapped areas for future work across a range of topics in physiology. First, we explore the impact that the loss of the Y chromosome in white blood cells has on men's health. Next, we discuss the pathophysiological roles of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) in chronic inflammation. Third, we discuss how certain animals remain hydrated in seawater. Finally, we present on the systemic reprogramming of endothelial cell signaling in metastasis and cachexia...

No abstract text is available yet for this article.

Proliferating cancer cells secrete a multitude of factors impacting metabolism, interorgan communication, and tumor progression. The distribution of tumor-derived factors to distant organs occurs via the circulation, which provides an extensive reactive surface lined by endothelial cells. Primary tumor-derived proteins impact cancer progression by modulating endothelial cell activation at the (pre-)metastatic niche, which affects tumor cell dissemination as well as the outgrowth of seeded metastatic cells into overt tumors...

DNA is a remarkable biochemical macromolecule tasked with storing the genetic information that instructs life on planet Earth. However, its inherent chemical instability within the cellular milieu is incompatible with the accurate transmission of genetic information to subsequent generations. Therefore, biochemical pathways that continuously survey and repair DNA are essential to sustain life, and the fundamental mechanisms by which different DNA lesions are repaired have remained well conserved throughout evolution...

Cellular senescence plays a central role in aging and geriatric diseases. Senolysis is a promising new strategy that selectively kills and eliminates senescent cells to control aging. To date, various senolytic drugs have been discovered and shown efficacy. This review highlights how we can benefit from senolysis.

No abstract text is available yet for this article.