Physiological reviews最新文献_第10页

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 Epub Date: 2023-01-05 DOI: 10.1152/physrev.00053.2021

Michael J Davis, Scott Earley, Yi-Shuan Li, Shu Chien

{"title":"Vascular mechanotransduction.","authors":"Michael J Davis, Scott Earley, Yi-Shuan Li, Shu Chien","doi":"10.1152/physrev.00053.2021","DOIUrl":"10.1152/physrev.00053.2021","url":null,"abstract":"This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), including their sensing of mechanical stimuli and transduction of mechanical signals that result in the acute functional modulation and longer-term transcriptomic and epigenetic regulation of blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures and receptors, and junction proteins. The mechanosignaling pathways presented include the cytoskeleton, integrins, extracellular matrix, and intracellular signaling molecules. These are followed by discussions on mechanical regulation of transcriptome and epigenetics, relevance of mechanotransduction to health and disease, and interactions between VSMCs and ECs. Throughout this review, we offer suggestions for specific topics that require further understanding. In the closing section on conclusions and perspectives, we summarize what is known and point out the need to treat the vasculature as a system, including not only VSMCs and ECs but also the extracellular matrix and other types of cells such as resident macrophages and pericytes, so that we can fully understand the physiology and pathophysiology of the blood vessel as a whole, thus enhancing the comprehension, diagnosis, treatment, and prevention of vascular diseases.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1247-1421"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10081054","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}

引用次数: 0

Contribution of adaptive immunity to human COPD and experimental models of emphysema. 适应性免疫对人类慢性阻塞性肺病和肺气肿实验模型的贡献。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 Epub Date: 2022-10-06 DOI: 10.1152/physrev.00036.2021

Farrah Kheradmand, Yun Zhang, David B Corry

{"title":"Contribution of adaptive immunity to human COPD and experimental models of emphysema.","authors":"Farrah Kheradmand, Yun Zhang, David B Corry","doi":"10.1152/physrev.00036.2021","DOIUrl":"10.1152/physrev.00036.2021","url":null,"abstract":"The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why emphysema progresses in a subset of former smokers remained a mystery for many years. The recognition of activated and organized tertiary T- and B-lymphoid aggregates in emphysematous lungs provided the first clue that adaptive immune cells may play a crucial role in COPD pathophysiology. Based on these findings from human translational studies, experimental animal models of emphysema were used to determine the mechanisms through which smoke exposure initiates and orchestrates adaptive autoreactive inflammation in the lungs. These models have revealed that T helper (Th)1 and Th17 subsets promote a positive feedback loop that activates innate immune cells, confirming their role in emphysema pathogenesis. Results from genetic studies and immune-based discoveries have further provided strong evidence for autoimmunity induction in smokers with emphysema. These new findings offer a novel opportunity to explore the mechanisms underlying the inflammatory landscape in the COPD lung and offer insights for development of precision-based treatment to halt lung destruction.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1059-1093"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696504","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}

引用次数: 0

Examining the shared etiology of psychopathology with genome-wide association studies. 通过全基因组关联研究探讨精神病理学的共同病因。

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-04-01 Epub Date: 2023-01-12 DOI: 10.1152/physrev.00016.2022

Travis T Mallard, Andrew D Grotzinger, Jordan W Smoller

{"title":"Examining the shared etiology of psychopathology with genome-wide association studies.","authors":"Travis T Mallard, Andrew D Grotzinger, Jordan W Smoller","doi":"10.1152/physrev.00016.2022","DOIUrl":"10.1152/physrev.00016.2022","url":null,"abstract":"Genome-wide association studies (GWASs) have ushered in a new era of reproducible discovery in psychiatric genetics. The field has now identified hundreds of common genetic variants that are associated with mental disorders, and many of them influence more than one disorder. By advancing the understanding of causal biology underlying psychopathology, GWAS results are poised to inform the development of novel therapeutics, stratification of at-risk patients, and perhaps even the revision of top-down classification systems in psychiatry. Here, we provide a concise review of GWAS findings with an emphasis on findings that have elucidated the shared genetic etiology of psychopathology, summarizing insights at three levels of analysis: 1) genome-wide architecture; 2) networks, pathways, and gene sets; and 3) individual variants/genes. Three themes emerge from these efforts. First, all psychiatric phenotypes are heritable, highly polygenic, and influenced by many pleiotropic variants with incomplete penetrance. Second, GWAS results highlight the broad etiological roles of neuronal biology, system-wide effects over localized effects, and early neurodevelopment as a critical period. Third, many loci that are robustly associated with multiple forms of psychopathology harbor genes that are involved in synaptic structure and function. Finally, we conclude our review by discussing the implications that GWAS results hold for the field of psychiatry, as well as expected challenges and future directions in the next stage of psychiatric genetics.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1645-1665"},"PeriodicalIF":29.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9464039","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}

引用次数: 0

Windows into stress: a glimpse at emerging roles for CRH^PVN neurons. 压力的窗口:对CRHPVN神经元新角色的一瞥。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 DOI: 10.1152/physrev.00056.2021

Neilen P Rasiah, Spencer P Loewen, Jaideep S Bains

引用次数: 1

The enteric nervous system. 肠道神经系统

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 Epub Date: 2022-12-15 DOI: 10.1152/physrev.00018.2022

Keith A Sharkey, Gary M Mawe

{"title":"The enteric nervous system.","authors":"Keith A Sharkey, Gary M Mawe","doi":"10.1152/physrev.00018.2022","DOIUrl":"10.1152/physrev.00018.2022","url":null,"abstract":"Of all the organ systems in the body, the gastrointestinal tract is the most complicated in terms of the numbers of structures involved, each with different functions, and the numbers and types of signaling molecules utilized. The digestion of food and absorption of nutrients, electrolytes, and water occurs in a hostile luminal environment that contains a large and diverse microbiota. At the core of regulatory control of the digestive and defensive functions of the gastrointestinal tract is the enteric nervous system (ENS), a complex system of neurons and glia in the gut wall. In this review, we discuss 1) the intrinsic neural control of gut functions involved in digestion and 2) how the ENS interacts with the immune system, gut microbiota, and epithelium to maintain mucosal defense and barrier function. We highlight developments that have revolutionized our understanding of the physiology and pathophysiology of enteric neural control. These include a new understanding of the molecular architecture of the ENS, the organization and function of enteric motor circuits, and the roles of enteric glia. We explore the transduction of luminal stimuli by enteroendocrine cells, the regulation of intestinal barrier function by enteric neurons and glia, local immune control by the ENS, and the role of the gut microbiota in regulating the structure and function of the ENS. Multifunctional enteric neurons work together with enteric glial cells, macrophages, interstitial cells, and enteroendocrine cells integrating an array of signals to initiate outputs that are precisely regulated in space and time to control digestion and intestinal homeostasis.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1487-1564"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469295","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}

引用次数: 0

Chloride transporters controlling neuronal excitability. 氯离子转运体控制神经元兴奋性。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 DOI: 10.1152/physrev.00025.2021

Jessica C Pressey, Miranda de Saint-Rome, Vineeth A Raveendran, Melanie A Woodin

{"title":"Chloride transporters controlling neuronal excitability.","authors":"Jessica C Pressey, Miranda de Saint-Rome, Vineeth A Raveendran, Melanie A Woodin","doi":"10.1152/physrev.00025.2021","DOIUrl":"https://doi.org/10.1152/physrev.00025.2021","url":null,"abstract":"Synaptic inhibition plays a crucial role in regulating neuronal excitability, which is the foundation of nervous system function. This inhibition is largely mediated by the neurotransmitters GABA and glycine that activate Cl--permeable ion channels, which means that the strength of inhibition depends on the Cl- gradient across the membrane. In neurons, the Cl- gradient is primarily mediated by two secondarily active cation-chloride cotransporters (CCCs), NKCC1 and KCC2. CCC-mediated regulation of the neuronal Cl- gradient is critical for healthy brain function, as dysregulation of CCCs has emerged as a key mechanism underlying neurological disorders including epilepsy, neuropathic pain, and autism spectrum disorder. This review begins with an overview of neuronal chloride transporters before explaining the dependent relationship between these CCCs, Cl- regulation, and inhibitory synaptic transmission. We then discuss the evidence for how CCCs can be regulated, including by activity and their protein interactions, which underlie inhibitory synaptic plasticity. For readers who may be interested in conducting experiments on CCCs and neuronal excitability, we have included a section on techniques for estimating and recording intracellular Cl-, including their advantages and limitations. Although the focus of this review is on neurons, we also examine how Cl- is regulated in glial cells, which in turn regulate neuronal excitability through the tight relationship between this nonneuronal cell type and synapses. Finally, we discuss the relatively extensive and growing literature on how CCC-mediated neuronal excitability contributes to neurological disorders.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1095-1135"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10681608","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}

引用次数: 7

Adaptation in auditory processing. 听觉处理中的适应。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 DOI: 10.1152/physrev.00011.2022

Benjamin D B Willmore, Andrew J King

{"title":"Adaptation in auditory processing.","authors":"Benjamin D B Willmore, Andrew J King","doi":"10.1152/physrev.00011.2022","DOIUrl":"https://doi.org/10.1152/physrev.00011.2022","url":null,"abstract":"Adaptation is an essential feature of auditory neurons, which reduces their responses to unchanging and recurring sounds and allows their response properties to be matched to the constantly changing statistics of sounds that reach the ears. As a consequence, processing in the auditory system highlights novel or unpredictable sounds and produces an efficient representation of the vast range of sounds that animals can perceive by continually adjusting the sensitivity and, to a lesser extent, the tuning properties of neurons to the most commonly encountered stimulus values. Together with attentional modulation, adaptation to sound statistics also helps to generate neural representations of sound that are tolerant to background noise and therefore plays a vital role in auditory scene analysis. In this review, we consider the diverse forms of adaptation that are found in the auditory system in terms of the processing levels at which they arise, the underlying neural mechanisms, and their impact on neural coding and perception. We also ask what the dynamics of adaptation, which can occur over multiple timescales, reveal about the statistical properties of the environment. Finally, we examine how adaptation to sound statistics is influenced by learning and experience and changes as a result of aging and hearing loss.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1025-1058"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10690761","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}

引用次数: 8

CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond. CGRP 生理、药理和治疗目标：偏头痛及其他。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 Epub Date: 2022-12-01 DOI: 10.1152/physrev.00059.2021

Andrew F Russo, Debbie L Hay

{"title":"CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.","authors":"Andrew F Russo, Debbie L Hay","doi":"10.1152/physrev.00059.2021","DOIUrl":"10.1152/physrev.00059.2021","url":null,"abstract":"Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons as well as in other cell types, such as motor neurons and neuroendocrine cells. CGRP acts via at least two G protein-coupled receptors that form unusual complexes with receptor activity-modifying proteins. These are the CGRP receptor and the AMY1 receptor; in rodents, additional receptors come into play. Although CGRP is known to produce many effects, the precise molecular identity of the receptor(s) that mediates CGRP effects is seldom clear. Despite the many enigmas still in CGRP biology, therapeutics that target the CGRP axis to treat or prevent migraine are a bench-to-bedside success story. This review provides a contextual background on the regulation and sites of CGRP expression and CGRP receptor pharmacology. The physiological actions of CGRP in the nervous system are discussed, along with updates on CGRP actions in the cardiovascular, pulmonary, gastrointestinal, immune, hematopoietic, and reproductive systems and metabolic effects of CGRP in muscle and adipose tissues. We cover how CGRP in these systems is associated with disease states, most notably migraine. In this context, we discuss how CGRP actions in both the peripheral and central nervous systems provide a basis for therapeutic targeting of CGRP in migraine. Finally, we highlight potentially fertile ground for the development of additional therapeutics and combinatorial strategies that could be designed to modulate CGRP signaling for migraine and other diseases.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1565-1644"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871059","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}

引用次数: 0

The physiological functions of human peroxisomes. 人体过氧化物酶体的生理功能。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 DOI: 10.1152/physrev.00051.2021

Ronald J A Wanders, Myriam Baes, Daniela Ribeiro, Sacha Ferdinandusse, Hans R Waterham

{"title":"The physiological functions of human peroxisomes.","authors":"Ronald J A Wanders, Myriam Baes, Daniela Ribeiro, Sacha Ferdinandusse, Hans R Waterham","doi":"10.1152/physrev.00051.2021","DOIUrl":"https://doi.org/10.1152/physrev.00051.2021","url":null,"abstract":"Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"957-1024"},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10400622","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}

引用次数: 20

Systematic reviews for basic scientists: a different beast. 基础科学家的系统评论:一个不同的野兽。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-09-01 DOI: 10.1152/physrev.00028.2022

John P A Ioannidis

引用次数: 7