Physiological reviews最新文献

{"title":"The role of quality metrics in the evolution of AI in health care and implications for generative AI.","authors":"Ryan C Godwin, Ryan L Melvin","doi":"10.1152/physrev.00029.2023","DOIUrl":"10.1152/physrev.00029.2023","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2873-2875"},"PeriodicalIF":33.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of SARS-CoV-2-associated anosmia.","authors":"Tatsuya Tsukahara, David H Brann, Sandeep Robert Datta","doi":"10.1152/physrev.00012.2023","DOIUrl":"10.1152/physrev.00012.2023","url":null,"abstract":"<p><p>Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory epithelium, current evidence suggests that neuronal infection is extremely rare in both the olfactory periphery and the brain, prompting the need for mechanistic models that can explain the widespread anosmia in COVID-19 patients. Starting from work identifying the non-neuronal cell types that are infected by SARS-CoV-2 in the olfactory system, we review the effects of infection of these supportive cells in the olfactory epithelium and in the brain and posit the downstream mechanisms through which sense of smell is impaired in COVID-19 patients. We propose that indirect mechanisms contribute to altered olfactory system function in COVID-19-associated anosmia, as opposed to neuronal infection or neuroinvasion into the brain. Such indirect mechanisms include tissue damage, inflammatory responses through immune cell infiltration or systemic circulation of cytokines, and downregulation of odorant receptor genes in olfactory sensory neurons in response to local and systemic signals. We also highlight key unresolved questions raised by recent findings.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2759-2766"},"PeriodicalIF":33.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10031889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic memory and CaMKII.","authors":"Roger A Nicoll, Howard Schulman","doi":"10.1152/physrev.00034.2022","DOIUrl":"10.1152/physrev.00034.2022","url":null,"abstract":"<p><p>Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and long-term potentiation (LTP) were discovered within a decade of each other and have been inextricably intertwined ever since. However, like many marriages, it has had its up and downs. Based on the unique biochemical properties of CaMKII, it was proposed as a memory molecule before any physiological linkage was made to LTP. However, as reviewed here, the convincing linkage of CaMKII to synaptic physiology and behavior took many decades. New technologies were critical in this journey, including in vitro brain slices, mouse genetics, single-cell molecular genetics, pharmacological reagents, protein structure, and two-photon microscopy, as were new investigators attracted by the exciting challenge. This review tracks this journey and assesses the state of this marriage 40 years on. The collective literature impels us to propose a relatively simple model for synaptic memory involving the following steps that drive the process: <i>1</i>) Ca²⁺ entry through <i>N</i>-methyl-d-aspartate (NMDA) receptors activates CaMKII. <i>2</i>) CaMKII undergoes autophosphorylation resulting in constitutive, Ca²⁺-independent activity and exposure of a binding site for the NMDA receptor subunit GluN2B. <i>3</i>) Active CaMKII translocates to the postsynaptic density (PSD) and binds to the cytoplasmic C-tail of GluN2B. <i>4</i>) The CaMKII-GluN2B complex initiates a structural rearrangement of the PSD that may involve liquid-liquid phase separation. <i>5</i>) This rearrangement involves the PSD-95 scaffolding protein, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), and their transmembrane AMPAR-regulatory protein (TARP) auxiliary subunits, resulting in an accumulation of AMPARs in the PSD that underlies synaptic potentiation. <i>6</i>) The stability of the modified PSD is maintained by the stability of the CaMKII-GluN2B complex. <i>7</i>) By a process of subunit exchange or interholoenzyme phosphorylation CaMKII maintains synaptic potentiation in the face of CaMKII protein turnover. There are many other important proteins that participate in enlargement of the synaptic spine or modulation of the steps that drive and maintain the potentiation. In this review we critically discuss the data underlying each of the steps. As will become clear, some of these steps are more firmly grounded than others, and we provide suggestions as to how the evidence supporting these steps can be strengthened or, based on the new data, be replaced. Although the journey has been a long one, the prospect of having a detailed cellular and molecular understanding of learning and memory is at hand.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2877-2925"},"PeriodicalIF":33.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria in health, disease, and aging.","authors":"John S Harrington, Stefan W Ryter, Maria Plataki, David R Price, Augustine M K Choi","doi":"10.1152/physrev.00058.2021","DOIUrl":"10.1152/physrev.00058.2021","url":null,"abstract":"<p><p>Mitochondria are well known as organelles responsible for the maintenance of cellular bioenergetics through the production of ATP. Although oxidative phosphorylation may be their most important function, mitochondria are also integral for the synthesis of metabolic precursors, calcium regulation, the production of reactive oxygen species, immune signaling, and apoptosis. Considering the breadth of their responsibilities, mitochondria are fundamental for cellular metabolism and homeostasis. Appreciating this significance, translational medicine has begun to investigate how mitochondrial dysfunction can represent a harbinger of disease. In this review, we provide a detailed overview of mitochondrial metabolism, cellular bioenergetics, mitochondrial dynamics, autophagy, mitochondrial damage-associated molecular patterns, mitochondria-mediated cell death pathways, and how mitochondrial dysfunction at any of these levels is associated with disease pathogenesis. Mitochondria-dependent pathways may thereby represent an attractive therapeutic target for ameliorating human disease.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2349-2422"},"PeriodicalIF":29.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging physiology and artificial intelligence to deliver advancements in health care.","authors":"Angela Zhang, Zhenqin Wu, Eric Wu, Matthew Wu, Michael P Snyder, James Zou, Joseph C Wu","doi":"10.1152/physrev.00033.2022","DOIUrl":"10.1152/physrev.00033.2022","url":null,"abstract":"<p><p>Artificial intelligence in health care has experienced remarkable innovation and progress in the last decade. Significant advancements can be attributed to the utilization of artificial intelligence to transform physiology data to advance health care. In this review, we explore how past work has shaped the field and defined future challenges and directions. In particular, we focus on three areas of development. First, we give an overview of artificial intelligence, with special attention to the most relevant artificial intelligence models. We then detail how physiology data have been harnessed by artificial intelligence to advance the main areas of health care: automating existing health care tasks, increasing access to care, and augmenting health care capabilities. Finally, we discuss emerging concerns surrounding the use of individual physiology data and detail an increasingly important consideration for the field, namely the challenges of deploying artificial intelligence models to achieve meaningful clinical impact.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2423-2450"},"PeriodicalIF":29.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10292159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis.","authors":"Rikke Nørregaard, Henricus A M Mutsaers, Jørgen Frøkiær, Tae-Hwan Kwon","doi":"10.1152/physrev.00027.2022","DOIUrl":"10.1152/physrev.00027.2022","url":null,"abstract":"<p><p>The kidneys play a key role in maintaining total body homeostasis. The complexity of this task is reflected in the unique architecture of the organ. Ureteral obstruction greatly affects renal physiology by altering hemodynamics, changing glomerular filtration and renal metabolism, and inducing architectural malformations of the kidney parenchyma, most importantly renal fibrosis. Persisting pathological changes lead to chronic kidney disease, which currently affects ∼10% of the global population and is one of the major causes of death worldwide. Studies on the consequences of ureteral obstruction date back to the 1800s. Even today, experimental unilateral ureteral obstruction (UUO) remains the standard model for tubulointerstitial fibrosis. However, the model has certain limitations when it comes to studying tubular injury and repair, as well as a limited potential for human translation. Nevertheless, ureteral obstruction has provided the scientific community with a wealth of knowledge on renal (patho)physiology. With the introduction of advanced omics techniques, the classical UUO model has remained relevant to this day and has been instrumental in understanding renal fibrosis at the molecular, genomic, and cellular levels. This review details key concepts and recent advances in the understanding of obstructive nephropathy, highlighting the pathophysiological hallmarks responsible for the functional and architectural changes induced by ureteral obstruction, with a special emphasis on renal fibrosis.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2827-2872"},"PeriodicalIF":33.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10498781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.","authors":"Michael D Roberts, John J McCarthy, Troy A Hornberger, Stuart M Phillips, Abigail L Mackey, Gustavo A Nader, Marni D Boppart, Andreas N Kavazis, Paul T Reidy, Riki Ogasawara, Cleiton A Libardi, Carlos Ugrinowitsch, Frank W Booth, Karyn A Esser","doi":"10.1152/physrev.00039.2022","DOIUrl":"10.1152/physrev.00039.2022","url":null,"abstract":"<p><p>Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of \"work-induced hypertrophy\" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2679-2757"},"PeriodicalIF":29.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology of intracellular calcium buffering.","authors":"David Eisner, Erwin Neher, Holger Taschenberger, Godfrey Smith","doi":"10.1152/physrev.00042.2022","DOIUrl":"10.1152/physrev.00042.2022","url":null,"abstract":"<p><p>Calcium signaling underlies much of physiology. Almost all the Ca²⁺ in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels in most cells. Physiological Ca²⁺ buffers include small molecules and proteins, and experimentally Ca²⁺ indicators will also buffer calcium. The chemistry of interactions between Ca²⁺ and buffers determines the extent and speed of Ca²⁺ binding. The physiological effects of Ca²⁺ buffers are determined by the kinetics with which they bind Ca²⁺ and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca²⁺, the Ca²⁺ concentration, and whether Ca²⁺ ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca²⁺ signals as well as changes of Ca²⁺ concentration in organelles. It can also facilitate Ca²⁺ diffusion inside the cell. Ca²⁺ buffering affects synaptic transmission, muscle contraction, Ca²⁺ transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation and tetanic contraction in skeletal muscle and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca²⁺ buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2767-2845"},"PeriodicalIF":29.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10063457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology of sedentary behavior.","authors":"Ana J Pinto, Audrey Bergouignan, Paddy C Dempsey, Hamilton Roschel, Neville Owen, Bruno Gualano, David W Dunstan","doi":"10.1152/physrev.00022.2022","DOIUrl":"10.1152/physrev.00022.2022","url":null,"abstract":"<p><p>Sedentary behaviors (SB) are characterized by low energy expenditure while in a sitting or reclining posture. Evidence relevant to understanding the physiology of SB can be derived from studies employing several experimental models: bed rest, immobilization, reduced step count, and reducing/interrupting prolonged SB. We examine the relevant physiological evidence relating to body weight and energy balance, intermediary metabolism, cardiovascular and respiratory systems, the musculoskeletal system, the central nervous system, and immunity and inflammatory responses. Excessive and prolonged SB can lead to insulin resistance, vascular dysfunction, shift in substrate use toward carbohydrate oxidation, shift in muscle fiber from oxidative to glycolytic type, reduced cardiorespiratory fitness, loss of muscle mass and strength and bone mass, and increased total body fat mass and visceral fat depot, blood lipid concentrations, and inflammation. Despite marked differences across individual studies, longer term interventions aimed at reducing/interrupting SB have resulted in small, albeit marginally clinically meaningful, benefits on body weight, waist circumference, percent body fat, fasting glucose, insulin, HbA1c and HDL concentrations, systolic blood pressure, and vascular function in adults and older adults. There is more limited evidence for other health-related outcomes and physiological systems and for children and adolescents. Future research should focus on the investigation of molecular and cellular mechanisms underpinning adaptations to increasing and reducing/interrupting SB and the necessary changes in SB and physical activity to impact physiological systems and overall health in diverse population groups.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 4","pages":"2561-2622"},"PeriodicalIF":29.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10287901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative physiological anthropogeny: exploring molecular underpinnings of distinctly human phenotypes.","authors":"Michael Vaill, Kunio Kawanishi, Nissi Varki, Pascal Gagneux, Ajit Varki","doi":"10.1152/physrev.00040.2021","DOIUrl":"10.1152/physrev.00040.2021","url":null,"abstract":"<p><p>Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of the human species. Comparative anthropogeny is a systematic comparison of humans and other living nonhuman hominids (so-called \"great apes\"), aiming to identify distinctly human features in health and disease, with the overall goal of explaining human origins. We begin with a historical perspective, briefly describing how the field progressed from the earliest evolutionary insights to the current emphasis on in-depth molecular and genomic investigations of \"human-specific\" biology and an increased appreciation for cultural impacts on human biology. While many such genetic differences between humans and other hominids have been revealed over the last two decades, this information remains insufficient to explain the most distinctive phenotypic traits distinguishing humans from other living hominids. Here we undertake a complementary approach of \"comparative physiological anthropogeny,\" along the lines of the preclinical medical curriculum, i.e., beginning with anatomy and considering each physiological system and in each case considering genetic and molecular components that are relevant. What is ultimately needed is a systematic comparative approach at all levels from molecular to physiological to sociocultural, building networks of related information, drawing inferences, and generating testable hypotheses. The concluding section will touch on distinctive considerations in the study of human evolution, including the importance of gene-culture interactions.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 3","pages":"2171-2229"},"PeriodicalIF":29.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9457540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}