Journal of Physiology-London最新文献

{"title":"Bridging the gap: Mean capillary-to-muscle diffusion distance as a limitation for oxygen uptake and metabolite exchange?","authors":"Laure Haenebalcke, Jeppe F Vigh-Larsen","doi":"10.1113/JP289674","DOIUrl":"https://doi.org/10.1113/JP289674","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compromised cardiopulmonary transition in fetal growth restricted and small for gestational age neonates.","authors":"Zahrah Azman, Arvind Sehgal, Suzanne L Miller, Kristen J Bubb, Graeme R Polglase, Beth J Allison","doi":"10.1113/JP289441","DOIUrl":"https://doi.org/10.1113/JP289441","url":null,"abstract":"<p><p>The cardiopulmonary transition at birth is a critical physiological process requiring coordinated cardiovascular adaptation to meet the increased circulatory demands of extrauterine life. This transition may be compromised in infants affected by suboptimal fetal growth, such as in infants born small for gestational age (SGA) or classified with fetal growth restriction (FGR). Suboptimal fetal growth often arises from reduced oxygen and nutrient supply, leading to prioritised perfusion of crucial organs and subsequent cardiac and arterial remodelling. These cardiovascular adaptations, while necessary for fetal survival, may persist postnatally and increase the risk of an impaired cardiovascular transition at birth. Altered echocardiographic function and cardiac injury biomarkers are often detectable in this population during the early postnatal period, indicating underlying myocardial stress and a predisposition to an impaired transition. FGR and/or SGA neonates often exhibit impaired diastolic function, reflecting impaired myocardial relaxation and reduced compliance, and systolic dysfunction, including a reduced capacity to increase left ventricular output over time. Additionally, elevated pulmonary vascular resistance contributes to an increased risk of respiratory morbidity. Emerging preclinical data suggest that these adaptations may impede the neonate's ability to respond to perinatal stressors, thus increasing the risk of adverse outcomes. Understanding the multifaceted nature of cardiovascular dysfunction in FGR and/or SGA infants during the perinatal period is essential to improving their long-term outcomes, thus reducing the risk of cardiovascular disease later in life.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of neurometabolites in sensory processing brain areas during motor learning","authors":"Hong Li,&nbsp;Amirhossein Rasooli,&nbsp;Geraldine Rodríguez-Nieto,&nbsp;Mark Mikkelsen,&nbsp;Dante Mantini,&nbsp;Stefan Sunaert,&nbsp;Sima Chalavi,&nbsp;Stephan P. Swinnen","doi":"10.1113/JP287349","DOIUrl":"10.1113/JP287349","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;GABA and glutamate (Glu) play pivotal roles in learning. Here, we investigated whether neurometabolites in specific sensory processing brain areas were differentially modulated depending on the type of feedback provided during motor learning and whether this was associated with behavioural progress. Fifty healthy human adults were trained on a bimanual tracking task for 5 days (Day 1 to Day 5) when receiving either concurrent (CA-VFB) or terminal (TA-VFB) augmented visual feedback. In two brain areas involved in sensory processing, that is the primary somatosensory cortex (S1) and medial temporal visual area (MT/V5), concentrations of GABA+ (GABA + macromolecules) and Glx (Glu + glutamine) were determined by acquiring magnetic resonance spectroscopy at three time points on Day 1 and Day 5: baseline (Pre-Scan), during (Mid-Scan) and after (Post-Scan) task training. Behaviourally, performance progress was more pronounced on Day 1 compared to Day 5. Neurochemically, there was a significant difference in the modulation of neurometabolites between the S1 and MT/V5 regions, specifically in Glx levels on Day 1. Additionally, there was a significant difference in the modulation of neurometabolites between Day 1 and Day 5, specifically in GABA+ levels in the S1 area and Glx levels in the MT/V5 area. Furthermore, a greater increase in individual S1 Glx levels on Day 5 correlated with larger behavioural progress. Our findings suggest that neurometabolites in task-related sensory processing brain areas show a differential modulation and contribute to long-term retention of visuomotor learning.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;GABA and glutamate play crucial roles in motor learning, yet how these neurometabolites are modulated within specific sensory processing brain regions based on the type of feedback provided during different phases of motor learning remains unclear.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We used a repeated measures magnetic resonance spectroscopy design to measure the concentration of neurometabolites in the primary somatosensory cortex (S1) and medial temporal visual area (MT/V5) before, during and after motor training, focusing on the initial and late learning phases.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;In the initial learning phase, Glx (glutamate + glutamine) modulation differed between S1 and MT/V5. Furthermore, in S1, GABA modulation differed between the initial and late phases, and, in MT/V5, Glx modulation also varied between these phases. A greater increase in individual S1 Glx levels on Day 5 co","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5681-5700"},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clenbuterol induces lean mass and muscle protein accretion, but attenuates cardiorespiratory fitness and desensitizes muscle β2-adrenergic signalling","authors":"Morten Hostrup,&nbsp;Lukas Moesgaard,&nbsp;Mads Fischer,&nbsp;Kate Aiko Wickham,&nbsp;Mads Pleshardt,&nbsp;Andreas Breenfeldt Andersen,&nbsp;Jacob Bejder,&nbsp;Martin Thomassen,&nbsp;Jens J. Nielsen,&nbsp;Yvette Dehnes,&nbsp;Jens Bangsbo,&nbsp;Nikolai B. Nordsborg,&nbsp;Søren Jessen","doi":"10.1113/JP289023","DOIUrl":"10.1113/JP289023","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;The β&lt;sub&gt;2&lt;/sub&gt;-adrenergic agonist clenbuterol is widely abused because of its purported fat-burning actions, muscle accretion properties and performance enhancing effects, and yet it remains unexplored in randomized controlled trials. In the present study, we subjected 11 healthy men (aged 18–40 years) to two 2 week cycles of oral clenbuterol (80 µg day&lt;sup&gt;−1&lt;/sup&gt;) or placebo, separated by a 3 week washout. During each cycle, we assessed body composition, cardiorespiratory fitness, sprint power output, cardiac left ventricular mass and intravascular blood volume. We obtained vastus lateralis muscle biopsies and analysed them for protein content, 3-hydroxyacyl CoA dehydrogenase (HAD) activity, oxidative phosphorylation complex (OXPHOS) abundance, platelet endothelial cell adhesion molecule (PECAM-1) abundance and β&lt;sub&gt;2&lt;/sub&gt;-adrenergic signalling. Compared to placebo, clenbuterol induced a 0.91 kg lean mass gain (95% confidence interval = 0.02–1.81, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) but had no effect on fat mass. Clenbuterol reduced maximal oxygen uptake by 7% (&lt;i&gt;P&lt;/i&gt; &lt; 0.001) and exercise capacity by 4% (&lt;i&gt;P&lt;/i&gt; &lt; 0.001) but had no effects on sprint power output, left ventricular mass, intravascular blood volume or haemoglobin mass. Clenbuterol increased muscle protein content (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) and PECAM-1 abundance (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) but repressed HAD activity (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) and OXPHOS complex V abundance (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Clenbuterol markedly activated muscle protein kinase A (&lt;i&gt;P&lt;/i&gt; &lt; 0.001) and phosphorylated ribosomal protein S6 (Ser235/236) but this effect declined during the 2 week cycle. Although a 2 week clenbuterol cycle effectively induces lean mass gain and muscle protein accretion, it negatively affects cardiorespiratory fitness, represses muscle oxidative capacity, and induces tolerance in β&lt;sub&gt;2&lt;/sub&gt;-adrenergic signalling and ribosomal protein S6 phosphorylation. The adverse effects of clenbuterol along with its muscle anabolic actions justify its prohibition in elite sports.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Clenbuterol, a potent β&lt;sub&gt;2&lt;/sub&gt;-adrenergic agonist, has purported fat-burning and muscle accretion properties. However, its purported effects, along with its potential adverse effects on cardiorespiratory fitness, remain unexplored in humans.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A short 2 week clenbuterol cycle induces lean mass gain and muscle protein accretion in healthy young men.&lt;/li&gt;\u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5529-5545"},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP289023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMEM16A in gastrointestinal and vascular smooth muscle contractility.","authors":"Sadik Taskin Tas, Marc O Anderson, Onur Cil","doi":"10.1113/JP289160","DOIUrl":"10.1113/JP289160","url":null,"abstract":"<p><p>Calcium-activated Cl^- channels (CaCC) are widely expressed proteins which regulate various physiological functions. TMEM16A is a CaCC expressed in the gastrointestinal and cardiovascular systems, where it is a major regulator of tissue contraction. In this review we discuss recent advances on the roles of TMEM16A in gastrointestinal and vascular smooth muscle contractility, including its segment and cell type-specific effects. We also discuss recent physiological and pharmacological evidence suggesting potential therapeutic utility of TMEM16A modulators in gastrointestinal and cardiovascular diseases associated with altered smooth muscle contractility.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of baroreflex feedback loop in predictions of left ventricular growth: A multiscale finite element modelling study.","authors":"Hossein Sharifi, Mohammad Mehri, Kenneth S Campbell, Lik Chuan Lee, Jonathan F Wenk","doi":"10.1113/JP288649","DOIUrl":"10.1113/JP288649","url":null,"abstract":"<p><p>The heart functions within a complex system that adapts its function to alterations in loading via several mechanisms. For example, the baroreflex is a feedback loop that modulates the heart's function on a beat-to-beat basis to control arterial pressure. On the other hand, cardiac growth is an adaptive process that occurs over weeks or months in response to changes in left ventricular loading. In this study, we investigate the impact of a baroreflex feedback loop on left ventricular growth in simulations of valve disease. To achieve this, we integrated the effects of a baroreflex feedback loop and a growth algorithm into a beating multiscale finite element model of the left ventricle. Our integrated model replicated clinical measures of left ventricular growth in two types of valvular diseases - aortic stenosis and mitral regurgitation - at two different levels of severity for each case. Furthermore, our results showed that incorporating the effects of baroreflex control in simulations of left ventricular growth not only led to more realistic haemodynamics, but also impacted the magnitude of growth. Finally, our results suggest that the regulation of Ca²⁺ dynamics by the baroreflex is a crucial mechanism in adapting the myocardial cell in response to altered loading due to aortic stenosis and mitral regurgitation. KEY POINTS: The heart adapts its function in response to alterations in loading via short-term and long-term mechanisms. These mechanisms are essential for maintaining proper blood pressure in the vasculature (baroreflex) and homeostasis in the heart (ventricular growth). In this study, we investigate the impact of a baroreflex feedback loop on left ventricular growth in finite element simulations of valve disease. We showed that incorporating the effects of baroreflex control and ventricular growth not only led to more realistic haemodynamics, but also impacted the magnitude of growth. Our results suggest that the regulation of Ca²⁺ dynamics by the baroreflex is a crucial mechanism in adapting the myocardial cell in response to altered ventricular loading.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics, cerebral neurovascularity, and the role of circulating platelets in healthy ageing","authors":"Guilherme da Silva Rodrigues,&nbsp;Andressa Crystine da Silva Sobrinho","doi":"10.1113/JP289736","DOIUrl":"10.1113/JP289736","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5263-5265"},"PeriodicalIF":4.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosin-binding protein C slows cardiac myofibril relaxation kinetics","authors":"Alexey V. Dvornikov,&nbsp;Samantha P. Harris","doi":"10.1113/JP289201","DOIUrl":"10.1113/JP289201","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Mutations in cardiac myosin binding protein C (cMyBP-C) are a leading cause of hypertrophic cardiomyopathy (HCM). Patients with HCM often have reduced cMyBP-C expression, reduced protein phosphorylation, and diastolic dysfunction. Relaxation of a single myofibril in response to a sudden drop in activator calcium is biphasic, consisting of a slow isometric phase (&lt;i&gt;k&lt;/i&gt;&lt;sub&gt;REL&lt;/sub&gt;,&lt;sub&gt;slow&lt;/sub&gt;) followed by a fast exponential phase (&lt;i&gt;k&lt;/i&gt;&lt;sub&gt;REL&lt;/sub&gt;,&lt;sub&gt;fast&lt;/sub&gt;), considered to reflect cross-bridge-dependent and -independent processes, respectively. Here, we determined the effects of cMyBP-C on myofibril activation and relaxation kinetics by deleting the C0-C7 fragment of cMyBP-C and replacing it using our ‘cut-and-paste’ method. Results show that acute loss of C0-C7 desensitized myofilaments to Ca&lt;sup&gt;2+&lt;/sup&gt; and sped both phases of relaxation. Ligation of recombinant wild-type C0-C7 returned relaxation rates back to baseline, whereas ligation of phosphorylated cMyBP-C left the fast relaxation phase accelerated and increased the rate of activation in response to Ca&lt;sup&gt;2+&lt;/sup&gt; (&lt;i&gt;k&lt;/i&gt;&lt;sub&gt;ACT&lt;/sub&gt;). Mavacamten (Mava), an inhibitor of myosin, accelerated both phases of relaxation independently of the presence or absence of cMyBP-C. Finally, we found that a point mutation in the M-domain of cMyBP-C (L348P) slowed both phases of relaxation. Taken together, we report that cMyBP-C slows both phases of relaxation, suggesting that it affects relaxation via cross-bridge-dependent and -independent mechanisms.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Mutations in &lt;i&gt;MYBPC3&lt;/i&gt;, the gene encoding cardiac myosin-binding protein C, (cMyBP-C) occur in ∼20%–25% of patients with hypertrophic cardiomyopathy. The majority of these mutations lead to reduced cMyBP-C protein expression in sarcomeres (haploinsufficiency). Here we investigated effects of acute loss of cMyBP-C on relaxation kinetics in mouse cardiac myofibrils using our ‘cut and paste’ approach.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Results showed that cMyBP-C slows both phases of myofibril relaxation. Phosphorylation of cMyBP-C accelerated the fast phase of relaxation, whereas a point mutation (L348P) that increases the affinity of cMyBP-C for actin, significantly slowed both phases of relaxation.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Mavacamten, a myosin inhibitor, accelerated both phases of relaxation independently of cMyBP-C.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Overall, we interpret our results in terms of dual cross-bridge-dependent and cross-b","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5351-5368"},"PeriodicalIF":4.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteric glial S100B controls rhythmic colonic functions by regulating excitability and specificity in gut motor neurocircuits","authors":"Beatriz Thomasi,&nbsp;Rafaella Lavalle,&nbsp;Jonathon L. McClain,&nbsp;Julia Jamka,&nbsp;Luisa Seguella,&nbsp;Brian D. Gulbransen","doi":"10.1113/JP289410","DOIUrl":"10.1113/JP289410","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Patterns of gut motility, such as colonic motor complexes, are controlled by central pattern generators (CPG) in the enteric nervous system; however, the mechanisms that co-ordinate enteric neural networks underlying this behaviour remain unclear. Evidence from similar CPGs in the brain suggests that glia play key roles through mechanisms involving the S100 calcium-binding protein B (S100B). Enteric glia are abundant in enteric neural networks and engage in bi-directional interactions with neurons, but whether enteric glia shape enteric CPG behaviours through similar mechanisms remains unclear. Here, we show that S100B release by myenteric glia is necessary to sustain colonic motor complex behaviour in the gut. Calcium imaging experiments in whole mounts of myenteric plexus from &lt;i&gt;Wnt1&lt;/i&gt;&lt;sup&gt;Cre2GCaMP5g-tdTom&lt;/sup&gt; mice revealed that the effects of manipulating S100B using selective drugs are a result of changes in neuron and glial activity in myenteric neurocircuits. S100B exerts major regulatory effects over cholinergic neurons, which are considered essential for colonic motor complex initiation and control, and recordings in samples from &lt;i&gt;ChAT&lt;/i&gt;&lt;sup&gt;CreGCaMP5g-tdTom&lt;/sup&gt; mice showed that S100B regulates spontaneous activity among cholinergic neurons and their interactions with other neurons in myenteric networks. These results extend the concept of glia in CPGs to the gut by showing that enteric glial S100B is a critical regulator of rhythmic gut motor function that acts by modulating glial excitability, neuronal behaviours and functional connectivity among neurons. A deeper understanding of this previously unknown glial regulatory mechanism could, therefore, be important for advancing therapies for common gastrointestinal diseases.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Patterns of gut motility such as colonic motor complexes (CMC) are considered to be controlled by central pattern generators housed in the myenteric plexus of the enteric nervous system.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Brain central pattern generators studies suggest that glia play key roles through mechanisms involving the protein S100 calcium-binding protein B (S100B).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;This work identifies enteric glial S100B as a regulator of enteric glial and neuronal excitability, through mechanisms of Ca&lt;sup&gt;2&lt;/sup&gt;⁺ regulation that are independent of the RAGE (i.e. receptor for advanced glycation end-products) signalling pathway.&lt;/li&gt;\u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5723-5749"},"PeriodicalIF":4.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP289410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Learning to stand with delays alters sensorimotor control but does not cause instability when returning to natural balance","authors":"Liam H. Foulger,&nbsp;Xiyao Liu,&nbsp;Amin M. Nasrabadi,&nbsp;Calvin Z. Qiao,&nbsp;Mark G. Carpenter,&nbsp;Lyndia C. Wu,&nbsp;Jean-Sébastien Blouin","doi":"10.1113/JP288632","DOIUrl":"10.1113/JP288632","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;To maintain a bipedal posture, humans must compensate for inherent sensorimotor delays from neural conduction times and electromechanical delays. Ageing and certain neurological disorders increase these delays, so it is crucial that we adapt our control of balance to compensate for the uncertainty associated with acting on sensory information from the past. Although humans can adapt to imposed delays of 400 ms, the mechanisms underlying the adaptation process remain unknown because gross balance instability or errors are absent when returning to balancing without delays. To investigate this, we used a robotic balance simulator to impose delays of 250 ms while participants balanced upright. We characterized and modelled the adjustments in motor commands required to adapt to the addition and removal of delays. Following 20 min of adaptation, participants successfully maintained their balance with the imposed delay. When the delay was abruptly removed, participants remained upright with minimal changes in their whole-body oscillations, but we observed transient (5–20 s) spectral power increases between 1 and 2 Hz in the net ankle torque and lower limb muscle activity. Our computational model revealed that increased sensorimotor gains led to spectral changes in the balance motor commands. Our results indicate that increased sensorimotor gains are necessary to adapt balance control to longer delays and that these gains remained transiently elevated after the removal of the delays without resulting in postural instability. This highlights the remarkable adaptability of human balance control, revealing that the nervous system can flexibly adjust sensorimotor strategies to maintain balance under changing conditions.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;The human nervous system can adapt to sensorimotor delays, allowing us to maintain balance even though there are delays between sensed stimuli and our corrective motor actions.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;While balancing on a robotic simulator, participants exposed to a 250 ms delay between their self-generated motor commands and resulting whole-body motion exhibited initial difficulty maintaining balance and increased muscle (co)activation but adapted within minutes of exposure.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Despite no postural instability following the abrupt removal of the 250 ms delay, participants exhibited transient (5–20 s) increases in leg muscle activation and ankle torque power","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5629-5653"},"PeriodicalIF":4.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP288632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}