Physiology最新文献

Hormones orchestrate virtually all physiological processes in animals, and enable them to adjust internal responses to meet diverse physiological demands. Studies in both vertebrates and insects have uncovered many novel hormones and dissected the physiological mechanisms they regulate, demonstrating a remarkable conservation in endocrine signaling across the tree of life. In this review, we focus on recent advances in insect research, which have provided a more integrative view of the conserved interorgan communication networks that control physiology These new insights have been driven by experimental advantages inherent to insects, which over the past decades have aligned with new technologies and sophisticated genetic tools, to transform insect genetic models into a powerful testbed for posing new questions and exploring longstanding issues in endocrine research. Here, we illustrate how insect studies have addressed classic questions in three main areas-hormonal control of growth and development, neuroendocrine regulation of ion and water balance, and hormonal regulation of behavior and metabolism- and how these discoveries have illuminated our fundamental understanding of endocrine signaling in animals. The application of integrative physiology in insect systems to questions in endocrinology and physiology is expanding, and is poised to be a crucible of discovery, revealing fundamental mechanisms of hormonal regulation that underlie animal adaptations to their environments.

As life expectancy increases globally, the prevalence and severity of age-related disease has risen, significantly impacting patients' quality of life and increasing dependency on the health care system. Age-related diseases share several pathological commonalities, and emerging evidence suggests that targeting these biological processes ameliorate multiple age-related diseases. Immune aging plays a critical role in the pathogenesis of age-related diseases, given its involvement not only in controlling infection and cancer but also in facilitating tissue homeostasis and repair. Aging causes compositional and functional changes in both innate and adaptive immune cells, thereby significantly contributing to the pathogenesis of age-related disease and systemic low-grade inflammation, termed as "inflammaging." This review article aims to describe the current understanding of immune aging and its impact on age-related diseases with particular emphasis on kidney and autoimmune disease. Additionally, this review highlights tertiary lymphoid structures (TLS) as a hallmark of immune aging, exploring their roles in inflammation, tissue damage and potential therapeutic targeting.

Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and the sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls the switch of HSCs from a self-renewal state to a more differentiated state, but it is only recently that we have appreciated the importance of metabolic pathways in regulating the commitment of progenitors to distinct hematopoietic lineages. In the context of erythroid differentiation, an extensive network of metabolites, including amino acids, sugars, nucleotides, fatty acids, vitamins, and iron, is required for red blood cell (RBC) maturation. In this review, we highlight the multifaceted roles via which metabolites regulate physiological erythropoiesis as well as the effects of metabolic perturbations on erythroid lineage commitment and differentiation. Of note, the erythroid differentiation process is associated with an exceptional breadth of solute carrier (SLC) metabolite transporter upregulation. Finally, we discuss how recent research, revealing the critical impact of metabolic reprogramming in diseases of disordered and ineffective erythropoiesis, has created opportunities for the development of novel metabolic-centered therapeutic strategies.

Organism health relies on cell proliferation, migration, and differentiation. These universal processes depend on cytoplasmic reorganization driven notably by the cytoskeleton and its force-generating motors. Their activity generates forces that mechanically agitate the cell nucleus and its interior. New evidence from reproductive cell biology revealed that these cytoskeletal forces can be tuned to remodel nuclear membraneless compartments, known as biomolecular condensates, and regulate their RNA processing function for the success of subsequent cell division that is critical for fertility. Both cytoskeletal and nuclear condensate reorganization are common to numerous physiological and pathological contexts, raising the possibility that mechanical remodeling of nuclear condensates may be a much broader mechanism regulating their function. Here, we review this newfound mechanism of condensate remodeling and venture into the contexts of health and disease where it may be relevant, with a focus on reproduction, cancer, and premature aging.

Preterm birth remains a worldwide health concern because of ongoing challenges in prediction and prevention. Current predictors are limited by poor performance, need for invasive sampling, and an inability to identify patients in a timely fashion to allow for effective intervention. The multiple etiologies of preterm birth often have an inflammatory component. Thus, a deeper understanding of the inflammatory mechanisms involved in preterm birth may provide opportunities to identify new predictors of preterm birth. This review discusses the multiple etiologies of preterm birth, their links to inflammation, current predictors available, and new directions for the field.

RANKL and its cognate receptor RANK are crucial regulators of bone metabolism in physiological as well as in pathological conditions. Here we go through the works that unveiled the paramount role of this signaling pathway. We focus on the RANKL cytokine, whose alterations are responsible for rare and common bone diseases. We describe recent insights on the regulation of RANKL expression, which provide new hints for the pharmacological regulation of this molecule. Based on the multiple functions exerted by RANKL (within and outside the bone tissue), we advise caution regarding the potential unintended consequences of its inhibition.

Understanding physiological mechanisms of tolerance to heat exposure, and potential ways to improve such tolerance, is increasingly important in the context of ongoing climate change. We discuss the concept of heat tolerance in humans and experimental models (primarily rodents), including intracellular mechanisms and improvements in tolerance with heat acclimation.

Voltage-gated ion channels (VGICs) are pivotal in regulating electrical activity in excitable cells and are critical pharmaceutical targets for treating many diseases including cardiac arrhythmia and neuropathic pain. Despite their significance, challenges such as achieving target selectivity persist in VGIC drug development. Recent progress in deep learning, particularly diffusion models, has enabled the computational design of protein binders for any clinically relevant protein based solely on its structure. These developments coincide with a surge in experimental structural data for VGICs, providing a rich foundation for computational design efforts. This review explores the recent advancements in computational protein design using deep learning and diffusion methods, focusing on their application in designing protein binders to modulate VGIC activity. We discuss the potential use of these methods to computationally design protein binders targeting different regions of VGICs, including the pore domain, voltage-sensing domains, and interface with auxiliary subunits. We provide a comprehensive overview of the different design scenarios, discuss key structural considerations, and address the practical challenges in developing VGIC-targeting protein binders. By exploring these innovative computational methods, we aim to provide a framework for developing novel strategies that could significantly advance VGIC pharmacology and lead to the discovery of effective and safe therapeutics.