Function (Oxford, England)最新文献

{"title":"Megalin as a Metabolic Modulator in the Kidney and Beyond.","authors":"Rebekah J Nicholson, Nirupama Ramkumar, Aylin R Rodan","doi":"10.1093/function/zqae032","DOIUrl":"10.1093/function/zqae032","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiology of Human iPSC-derived Vascular Smooth Muscle Cells and Cell-autonomous Consequences of Cantú Syndrome Mutations.","authors":"Alex Hanson, Conor McClenaghan, Kuo-Chan Weng, Sarah Colijn, Amber N Stratman, Carmen M Halabi, Dorothy K Grange, Jonathan R Silva, Colin G Nichols","doi":"10.1093/function/zqae027","DOIUrl":"10.1093/function/zqae027","url":null,"abstract":"<p><p>Cantú syndrome (CS), a multisystem disease with a complex cardiovascular phenotype, is caused by gain-of-function (GoF) variants in the Kir6.1/SUR2 subunits of ATP-sensitive potassium (KATP) channels and is characterized by low systemic vascular resistance, as well as tortuous, dilated, vessels, and decreased pulse-wave velocity. Thus, CS vascular dysfunction is multifactorial, with both hypomyotonic and hyperelastic components. To dissect whether such complexities arise cell autonomously within vascular smooth muscle cells (VSMCs) or as secondary responses to the pathophysiological milieu, we assessed electrical properties and gene expression in human induced pluripotent stem cell-derived VSMCs (hiPSC-VSMCs), differentiated from control and CS patient-derived hiPSCs, and in native mouse control and CS VSMCs. Whole-cell voltage clamp of isolated aortic and mesenteric arterial VSMCs isolated from wild-type (WT) and Kir6.1[V65M] (CS) mice revealed no clear differences in voltage-gated K+ (Kv) or Ca2+ currents. Kv and Ca2+ currents were also not different between validated hiPSC-VSMCs differentiated from control and CS patient-derived hiPSCs. While pinacidil-sensitive KATP currents in control hiPSC-VSMCs were similar to those in WT mouse VSMCs, they were considerably larger in CS hiPSC-VSMCs. Under current-clamp conditions, CS hiPSC-VSMCs were also hyperpolarized, consistent with increased basal K conductance and providing an explanation for decreased tone and decreased vascular resistance in CS. Increased compliance was observed in isolated CS mouse aortae and was associated with increased elastin mRNA expression. This was consistent with higher levels of elastin mRNA in CS hiPSC-VSMCs and suggesting that the hyperelastic component of CS vasculopathy is a cell-autonomous consequence of vascular KATP GoF. The results show that hiPSC-VSMCs reiterate expression of the same major ion currents as primary VSMCs, validating the use of these cells to study vascular disease. Results in hiPSC-VSMCs derived from CS patient cells suggest that both the hypomyotonic and hyperelastic components of CS vasculopathy are cell-autonomous phenomena driven by KATP overactivity within VSMCs .</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11388097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing Sex as a Biological Variable in Physiological Research: Best Practices.","authors":"Candee T Barris, Emily Burns-Ray, Jennifer C Sullivan","doi":"10.1093/function/zqae034","DOIUrl":"10.1093/function/zqae034","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining Cytokine Responsive and Non-responsive Human β-cells.","authors":"Samuel B Stephens","doi":"10.1093/function/zqae039","DOIUrl":"https://doi.org/10.1093/function/zqae039","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MoTrPAC Animal Aerobic Exercise Protocol and Biorepository: A Novel Resource for Uncovering Systemic Adaptations to Aerobic Exercise and Extending Healthspan.","authors":"Robert T Mankowski, Raymond Jones, Thomas W Buford","doi":"10.1093/function/zqae040","DOIUrl":"10.1093/function/zqae040","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Circadian Changes in Muscle Physiology: Methodological Considerations.","authors":"Mark R Viggars, Karyn A Esser","doi":"10.1093/function/zqae038","DOIUrl":"https://doi.org/10.1093/function/zqae038","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malaria and Hypertension: What Is the Direction of Association?","authors":"Aparna Tiwari, Auley De, Abhinav Sinha","doi":"10.1093/function/zqae037","DOIUrl":"https://doi.org/10.1093/function/zqae037","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired neurocirculatory control in chronic kidney disease: New evidence for blunted sympathetic baroreflex and reduced sympathetic transduction.","authors":"Jeann L Sabino-Carvalho, Elsa Mekonnen, Matias Zanuzzi, Sabrina Li, Xiangqin Cui, Jeanie Park","doi":"10.1093/function/zqae036","DOIUrl":"https://doi.org/10.1093/function/zqae036","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is characterized by over-activation of the sympathetic nervous system (SNS) that increases cardiovascular risk. Whether sympathetic baroreflex sensitivity (sBRS) is impaired or intact in CKD remains under-studied and controversial. Furthermore, the downstream effect of SNS activation on blood pressure transduction has not been previously examined in CKD. We tested the hypothesis that sBRS is attenuated, while sympathetic transduction is augmented in CKD.</p><p><strong>Methods: </strong>In 18 sedentary patients with CKD stages III-IV (eGFR: 40±14 ml/min) and 13 age-matched controls (eGFR: 95±10 ml/min), beat-to-beat blood pressure (BP; finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest for 10-min. Weighted linear regression analysis between MSNA burst incidence and diastolic BP was used to determine the spontaneous sBRS. Sympathetic-BP transduction was quantified using signal averaging, whereby the BP response to each MSNA burst was tracked over 15 cardiac cycles and averaged to derive the peak change in BP.</p><p><strong>Results: </strong>Compared with controls, CKD patients had an attenuated sBRS [CKD: -1.34±0.59 versus CON: -2.91±1.09 bursts (100 heartbeats)-1 mmHg-1; P=0.001]. |sBRS| was significantly associated with eGFR (r=0.69, P<0.001). CKD patients had attenuated sympathetic-BP transduction compared to controls (0.75±0.7 vs. 1.60±0.8 mmHg; P=0.010). Resting MSNA was negatively associated with sympathetic transduction (r=-0.57, P=0.002).</p><p><strong>Conclusion: </strong>CKD patients exhibit impaired sBRS that may contribute to SNS overactivation and cardiovascular risk in this patient population. In addition, CKD patients had an attenuated sympathetic transduction that may counteract the vascular effects of SNS overactivation.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic Skeletal Muscle Function and Contraction-stimulated Glucose Uptake Do Not Vary by Time-of-day in Mice.","authors":"Liam S Fitzgerald, Shannon N Bremner, Samuel R Ward, Yoshitake Cho, Simon Schenk","doi":"10.1093/function/zqae035","DOIUrl":"10.1093/function/zqae035","url":null,"abstract":"<p><p>A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at four times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the four time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia.","authors":"Simonetta Falzoni, Valentina Vultaggio-Poma, Paola Chiozzi, Mario Tarantini, Elena Adinolfi, Paola Boldrini, Anna Lisa Giuliani, Giampaolo Morciano, Yong Tang, Dariusz C Gorecki, Francesco Di Virgilio","doi":"10.1093/function/zqae019","DOIUrl":"10.1093/function/zqae019","url":null,"abstract":"<p><p>Microparticles (MPs) are secreted by all cells, where they play a key role in intercellular communication, differentiation, inflammation, and cell energy transfer. P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) causes a large MP release and affects their contents in a cell-specific fashion. We investigated MP release and functional impact in microglial cells from P2X7R-WT or P2X7R-KO mice, as well as mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) P2X7R expression. P2X7R stimulation promoted release of a mixed MP population enriched with naked mitochondria. Released mitochondria were taken up and incorporated into the mitochondrial network of the recipient cells in a P2X7R-dependent fashion. NLRP3 and the P2X7R itself were also delivered to the recipient cells. Microparticle transfer increased the energy level of the recipient cells and conferred a pro-inflammatory phenotype. These data show that the P2X7R is a master regulator of intercellular organelle and MP trafficking in immune cells.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}