Journal of Physiology-London最新文献

{"title":"Cellular and molecular cross-talk in atrial fibrillation: The role of non-cardiomyocytes in creating an arrhythmogenic substrate.","authors":"Zhenyu Dong, Ruben Coronel, Joris R de Groot","doi":"10.1113/JP286978","DOIUrl":"https://doi.org/10.1113/JP286978","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is a complex arrhythmia. Various modulating factors influence its triggers and substrate. Fibroblasts, adipocytes, inflammatory cells and the coagulation system can disrupt cardiomyocyte function. Cardiomyocytes and fibroblasts release inflammatory cytokines that promote local and systemic inflammation, enhancing fibroblast activation and extracellular matrix deposition, leading to myocardial fibrosis. Fibrosis is essential for the induction of reentrant arrhythmias, including AF. Adipocytes contribute to arrhythmogenesis by secreting pro-inflammatory and pro-fibrotic factors, exacerbating inflammation and metabolic dysregulation. Inflammatory mediators activate the coagulation system, which augments this vicious cycle by producing factors promoting inflammation, fibrosis and arrhythmias at the same time as increasing the risk of thrombosis. Understanding these interconnected roles in the development and progress of the atrial arrhythmogenic substrate may point to potential novel therapeutic targets to stabilise or antagonise the atrial substrate and eventually prevent AF. This review examines the role of the interplay between cardiomyocytes, fibroblasts, adipocytes, inflammation and the coagulation system in contributing to the arrhythmogenic substrate for AF initiation and perpetuation.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573777","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":"Distinct age-related alterations in alpha-beta neural oscillatory activity during verbal working memory encoding in children and adolescents.","authors":"Augusto Diedrich, Yasra Arif, Brittany K Taylor, Zhiying Shen, Phillip M Astorino, Wai Hon Lee, Ryan W McCreery, Elizabeth Heinrichs-Graham","doi":"10.1113/JP287372","DOIUrl":"https://doi.org/10.1113/JP287372","url":null,"abstract":"<p><p>Emerging imaging studies of working memory (WM) have identified significant WM-related oscillatory events that are unique to each phase of working memory (e.g. encoding, maintenance). Although many previous imaging studies have shown age-related changes within the frontoparietal network when performing a WM task, understanding of the age-related changes in the oscillatory dynamics underlying each phase of WM during development and their relationships to other cognitive function is still in its infancy. To this end, we enrolled a group of 74 typically-developing youths aged 7-15 years to perform a letter-based Sternberg WM task during magnetoencephalography. Trial-wise data were transformed into the time-frequency domain, and significant oscillatory responses during the encoding and maintenance phases of the task were independently imaged using beamforming. Our results revealed widespread age-related power differences in alpha-beta oscillatory activity during encoding throughout left frontal, parietal, temporal, occipital and cerebellar regions. By contrast, age-related differences in maintenance-related activity were limited to a small area in the superior temporal gyrus and parieto-occipital regions. Follow-up exploratory factor analysis of age-related encoding alpha-beta activity revealed two distinct factors, and these factors were each found to significantly mediate age-related improvements in both verbal and non-verbal cognitive ability. Additionally, late maintenance alpha activity was related to reaction time on the task. Taken together, our results indicate that the neural dynamics in the alpha and beta bands are uniquely sensitive to age-related changes throughout this developmental period and are related to both task performance and other aspects of cognitive development. KEY POINTS: Understanding of the age-related changes in neural oscillatory dynamics serving verbal working memory function is in its infancy. This study identified the age-related neural alterations during each phase of working memory processing in youths. Developmental differences during working memory processing were primarily isolated to alpha-beta activity during the encoding phase. Alpha-beta activity during encoding significantly mediated age-related improvements in both verbal and non-verbal ability. This study establishes new brain-behaviour relationships linking working memory function to other aspects of cognitive development.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574303","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":"Mitochondrial proteostasis and cellular health: insights from chaperones and autophagy.","authors":"Yuvraj Anandrao Jagtap, Akash Choudhary, Sumit Kinger, Prashant Kumar, Sudipta Bhattacharyya, Hem Chandra Jha, Rohan Dhiman, Vivek Sharma, Anil K Suresh, Krishna Mohan Poluri, Amit Mishra","doi":"10.1113/JP287635","DOIUrl":"https://doi.org/10.1113/JP287635","url":null,"abstract":"<p><p>Mitochondria are a cell's powerhouse and also have a vital part in cellular processes. The emerging role of mitochondria in several crucial processes highlights their cellular and physiological importance. Mitochondrial homeostasis mechanisms, including proteostasis pathways, are vital for mitochondrial health. Failure of these processes has an important role in establishment of numerous complex disease conditions, such as neurodegeneration and imperfect ageing. However, details of mitochondrial impairments and their contribution to the pathology of neurodegeneration are poorly understood. This review systematically discusses the involvement of mitochondrial homeostasis mechanisms and their role in rejuvenating cellular health and fitness. We also focus on various cellular protein quality control mechanisms essential for mitochondrial proteostasis and how their failure leads to mitochondrial functional disturbances observed in disease conditions. We discuss recent findings based on mitostasis-associated chaperones, mitoproteases, and autophagy responses, which can lead to emergence of new possible therapeutic interventions against complex diseases.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568752","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":"The apical mucus layer alters the pharmacological properties of the airway epitheliumy.","authors":"Daniela Guidone, Martina de Santis, Emanuela Pesce, Valeria Capurro, Nicoletta Pedemonte, Luis J V Galietta","doi":"10.1113/JP287891","DOIUrl":"https://doi.org/10.1113/JP287891","url":null,"abstract":"<p><p>Electrogenic transepithelial ion transport can be measured with the short-circuit current technique. Such experiments are frequently used to evaluate the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that is defective in cystic fibrosis, one of the most frequent genetic diseases. Typically, CFTR activity is estimated from the effect of CFTR_inh-172, a selective CFTR inhibitor. Unexpectedly, we found that CFTR_inh-172, in addition to PPQ-102, another CFTR inhibitor, caused only partial inhibition of CFTR function, particularly in epithelia in pro-inflammatory conditions, which are characterized by abundant mucus secretion. We hypothesized that the mucus layer was responsible for the poor activity of CFTR inhibitors. Therefore, we treated the epithelial surface with the reducing agent dithiothreitol to remove mucus. Removal of mucus, confirmed by immunofluorescence, resulted in highly enhanced sensitivity of CFTR to pharmacological inhibition. Our results show that the mucus layer represents an important barrier whose presence limits the activity of pharmacological agents. This is particularly relevant for CFTR and the evaluation of therapeutic approaches for correction of the basic defect in cystic fibrosis. KEY POINTS: Activity of the cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel can be evaluated by measuring the inhibition elicited by the selective blockers CFTR_inh-172 and PPQ-102. In short-circuit current recordings on human airway epithelia, CFTR inhibitors had only a partial effect on cAMP-dependent chloride secretion, suggesting the possible contribution of other ion channels. The mucus layer covering the epithelial surface was removed with the reducing agent dithiothreitol. Treatment of epithelia with dithiothreitol markedly improved the efficacy of CFTR inhibitors. The partial effect of CFTR inhibitors might be explained by the presence of the mucus layer acting as a barrier.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568754","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":"The brain baroreflex - a hidden guardian of the cerebral circulation.","authors":"Christabel Osei-Boateng, Jenna C McCrone, Michael M Tymko","doi":"10.1113/JP288604","DOIUrl":"https://doi.org/10.1113/JP288604","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568756","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":"ESM-1 and GBP-1 are associated with endothelial dysfunction: emerging biomarkers or key players in the pathophysiology of preeclampsia?","authors":"Ines Pronk, Joost H N Schuitemaker, Marijke M Faas, Alexandra M Smink","doi":"10.1113/JP285934","DOIUrl":"https://doi.org/10.1113/JP285934","url":null,"abstract":"<p><p>Preeclampsia is a hypertensive disorder of pregnancy and is one of the most prevalent causes of maternal and fetal morbidity and mortality. The disease is thought to originate from impaired placental development or restricted villous perfusion, villous constraints and placental senescence at the end of pregnancy, which in turn cause defective placental functioning and eventually systemic endothelial dysfunction. Because the precise pathophysiology of this pregnancy complication is still not clear and diagnosis is only made when it is clinically visible, considerable research is being performed on biomolecules that could play a role in the development of the disease and could have a predictive, diagnostic or prognostic value. In the present review, we focus on two proteins, associated with endothelial dysfunction, which have changed levels in pregnant women during preeclampsia. These two proteins, endothelial specific molecule-1 (ESM-1) and guanylate binding protein-1 (GBP-1), are known to be involved in processes such as angiogenesis, inflammation and endothelial activation. ESM-1 is increased during preeclampsia and GBP-1 is decreased during preeclampsia, and their potential as biomarkers for preeclampsia could therefore be assessed. In addition to assessing their potential to serve as biomarkers, we will go into potential pathophysiological mechanisms of preeclampsia in which these proteins might be involved. We are proposing that ESM-1 and GBP-1 might play a role in impaired angiogenesis and vascular maladaptation, impaired immune regulation and oxidative stress, which ultimately could lead to endothelial dysfunction and preeclampsia.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568751","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":"Inhibition of ErbB2 mitigates secondary denervation after traumatic muscle injury.","authors":"Jacob R Sorensen, Daniel B Hoffman, Christiana J Raymond-Pope, Thomas J Lillquist, Amanda M Russell, Benjamin T Corona, Sarah M Greising","doi":"10.1113/JP287435","DOIUrl":"10.1113/JP287435","url":null,"abstract":"<p><p>Secondary denervation has recently been described as part of the sequela of volumetric muscle loss (VML) injury, occurring along with a significantly elevated neurotrophic response, specifically neuregulin-1 (NRG1). This may contribute to chronic functional impairments associated with the injury, representing an overlooked treatment target. Thus, though paradoxical, the goal of this study was to pharmacologically reduce neurotrophic signalling after VML using a monoclonal antibody (Herceptin) that inhibits ErbB2 receptors. We also assessed whether ErbB2 inhibition combined with a myogenic treatment (i.e. minced muscle graft) would have a synergistically beneficial effect on function. Adult male Lewis rats underwent surgical induction of tibialis anterior muscle VML injury and were randomized into one of four groups: VML untreated, VML Herceptin, VML muscle graft and VML muscle graft + Herceptin, with comparisons to the contralateral (uninjured) control muscle. Rats receiving Herceptin were administered the drug (8 mg/kg i.p.) at the time of surgery and thrice per week for the duration of the study (48 days). Terminally individual NMJs were quantitatively evaluated, and maximal in vivo torque was tested. ErbB2 inhibition fully restored the normal rates of NMJ innervation and morphology after VML injury, and improved innervation of de novo myofibres after a muscle-graft treatment. However ErbB2 inhibition did not improve skeletal muscle function alone or in combination with a muscle-graft treatment. We conclude that ErbB2 inhibition is a promising therapeutic option for treating VML injury, yet more work is needed to optimize the translation of improved NMJ characteristics to recover function. KEY POINTS: In cases of complex traumatic musculoskeletal injury, such as volumetric muscle loss (VML), the endogenous ability of skeletal muscle to regenerate and recover function is lost. Innervation, or the connection of a motor axon to each individual myofibre, is a necessary component of myofibre survival and contractile function, which is disrupted after VML. Paradoxically a monocolonal antibody inhibitor of neurotrophic signalling (receptor tyrosine kinase ErbB2; Herceptin) has been shown to improve regeneration in rodent models of nerve injury. Here we show that pharmaceutical ErbB2 inhibition following a rat model of VML improves muscle innervation; however it did not correspondingly recover muscle function. Although ErbB2 inhibition alone is an ineffective treatment for VML injury, its ability to improve innervation is noteworthy and should be considered as an adjunctive or combinatorial therapy option.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544397","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":"Ultrastructure of astrocytes using volume electron microscopy: A scoping review.","authors":"Vanessa Chiappini, Maria Fernanda Veloz Castillo, Francesco Biancardi, Ferdinando Di Cunto, Pierre J Magistretti, Alessandro Vercelli, Marco Agus, Corrado Calì","doi":"10.1113/JP287455","DOIUrl":"https://doi.org/10.1113/JP287455","url":null,"abstract":"<p><p>The morphological features of astrocytes are crucial for brain homeostasis, synaptic activity and structural support, yet remain poorly quantified. As a result of the nanometre-sized cross-section of neuropil astrocytic processes, electron microscopy (EM) is the only technique availabe to date capable of revealing their finest morphologies. Volume EM (vEM) techniques, such as serial block-face or focused ion beam scanning EM, enable high-resolution imaging of large fields and allow more extensive 3-D model analyses, revealing new astrocytic morphological features. This scoping review aims to summarize the state of the art of astrocyte ultrastructural analysis. This review included 45 of 439 non-duplicated articles from a Pubmed search, categorizing studies by research focus, animal models, brain region, vEM techniques and segmentation methods. By answering classical questions such as volume, surface area, branching complexity and synaptic ensheathment reported in the literature, this work is a valuable resource for scientists working on structural biology or computational neuroscience.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544381","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":"More strain, more brain: the impact of exercise intensity on neurogenesis.","authors":"Federico Picciau, Valdemar Brimnes Ingemann Johansen, Christoffer Merrild","doi":"10.1113/JP288408","DOIUrl":"https://doi.org/10.1113/JP288408","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544425","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":"The pathological blood flow steal phenomenon limits exercise tolerance in pulmonary hypertensive rats.","authors":"Júlia Teixeira Marinho, Bruno Brieda Marafon","doi":"10.1113/JP288421","DOIUrl":"https://doi.org/10.1113/JP288421","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544373","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}