The Journal of Physiology最新文献

{"title":"Developing in a polluted atmosphere: A link between long-term exposure to elevated atmospheric CO₂ and hyperactivity.","authors":"Helen Stolp","doi":"10.1113/JP282577","DOIUrl":"https://doi.org/10.1113/JP282577","url":null,"abstract":"The World Health Organisation (WHO) estimates that 99% of people worldwide breathe polluted air on a day-to-day basis (i.e. air with pollutant levels higher than WHO guidelines) and that ambient air pollution causes more than 4 million premature deaths per year. These numbers reflect the effect of particulate matter on cardiovascular and respiratory disease (Cohen et al. 2017) and probably underestimate the importance of air pollution on health because the role of atmospheric carbon dioxide (CO2) has not been considered thus far. Furthermore, air pollution has neurotoxic effects that are increasingly recognised and elevated atmospheric CO2 has the potential to cause renal and bone disease, expanding the latent health impact of air pollution globally. In this issue of The Journal of Physiology, Wyrwoll et al. (2022) address this timely question, exploring both systemic and neurological outcomes of a life lived in a high CO2 environment. Comparing life-time exposure to current atmospheric CO2 (460 ppm) with the higher CO2 level of 890 ppm, a level predicted to occur by the year 2100, Wyrwoll et al. (2022) showed that mice exposed to elevated CO2 during gestation had a higher birth weight than their control counterparts. Abnormal birth weight can increase risk of later morbidity, although, in this case, weight normalised over the postnatal period and developmental milestones, such as righting reflex or eye opening, were not delayed. Dimorphism occurred between males and females at adulthood, with high CO2 exposed females having lower body weight compared to age-matched controls. It is well known that substantial acute increases in inspired, or decreases in expired, CO2 result in respiratory acidosis, where the pH of the blood falls below the normal physiological range. Short-term compensations include increased respiration or altered renal excretion of hydrogen and bicarbonate ions. Longer-term, excess hydrogen can be buffered by bicarbonate released from bone. This bicarbonate release may lead to osteoporosis, whereas the accompanying release of calcium and other ions can contribute to renal calcification. It has been unclear until now whether increased atmospheric CO2 could drive these pathologies. This question is pertinent given that the world is experiencing unprecedented increases in atmospheric CO2. Surprisingly, no pathological changes were observed in kidney structure at adulthood following exposure to the high CO2 environment for 3 months (i.e. from gestation to young adulthood) or using measures of renal function (Wyrwoll et al. 2022). Nor were differences in bone structural density identified, as would be expected if substantial physiological compensation was occurring. This may reflect the relatively short experimental period and the fact that blood pH was only borderline acidotic in this model, although it was sufficient to change the structure and function of the lungs, as detailed in a companion study (Larcombe et al. 2021). Particul","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1275-1276"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39663908","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":"Nasal epithelial cells as a gold-standard predictive model for personalized medicine in cystic fibrosis.","authors":"Nicoletta Pedemonte","doi":"10.1113/JP282586","DOIUrl":"https://doi.org/10.1113/JP282586","url":null,"abstract":"Cystic fibrosis (CF) is caused by mutations impairing CFTR channel function. Over the last decade, novel drugs, called modulators, have been developed to rescue the basic defect caused by specific mutations. Unprecedented clinical results have been achieved in patients with eligible genotypes. However, CF is characterized by a remarkable allelic heterogeneity. Many patients cannot benefit yet from these treatments as in the case of patients carrying rare biallelic mutations, potentially responsive to modulators, but unable to be included in clinical trials due to the rarity of their mutations (Castellani, 2020). The use of in vitro models can significantly contribute to personalized therapeutic approaches in CF. Rectal biopsy-derived cells can develop intestinal organoids having a fluid-filled lumen.CFTR activation causes organoid swelling, and thus modulator efficacy can be evaluated by assessing their ability to restore swelling in CF organoids (Dekkers et al. 2013), as an indirect measure of CFTR function. While these models may address gastrointestinal features of CF patients, their relevance with regards to the pulmonary phenotypes is not unanimously recognized and the most reliable model to predict efficacy of CF therapies remains the airway epithelium. Since the availability of human CF bronchial (hBE) cells relies on patients undergoing lung transplant, human nasal epithelial (hNE) cells have emerged as a surrogate of airway epithelial cells for ex vivo testing of CF modulators (Pranke et al. 2017; Brewington et al. 2018). Conditional reprogramming culture allows the amplification of hNE cell number to study the molecular mechanisms causing CFTR dysfunction and responsiveness to drugs. In their recent study, Noel and colleagues (2022) investigated the amplitude and characteristics of CFTR-mediated currents in freshly isolated vs. conditionally reprogrammed hNE cells and compared them to the results obtained using in vivo assays to assess CFTR function in nasal epithelium (nasal potential difference (NPD) assay) and sweat gland (sweat Cl− concentration measurements). The utility and validity of hNE cell testing is still debated since it is not clear whether reprogrammed cells maintain the same CFTR expression level and activity as compared to native cells. With this aim, the authors performed whole-cell Cl− current recordings on freshly isolated and cultured hNE cells from non-CF or CF subjects before and after conditional reprogramming culture and compared the results with short-circuit current recordings in reprogrammed cells. In this way, the authors clearly demonstrated that there is perfect agreement between the two measurements. Interestingly, the authors also found that the amount of CFTR-mediated whole-cell Cl− current recorded in hNE cells from non-CF subjects was variable, in agreement with previous reports on bronchial epithelia (Eckford et al. 2014). Differences in genetic background are the most plausible explanation for the o","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1285-1286"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39941483","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":"Nutrient timing and metabolic regulation.","authors":"Harry A Smith,&nbsp;James A Betts","doi":"10.1113/JP280756","DOIUrl":"https://doi.org/10.1113/JP280756","url":null,"abstract":"<p><p>Daily (circadian) rhythms coordinate our physiology and behaviour with regular environmental changes. Molecular clocks in peripheral tissues (e.g. liver, skeletal muscle and adipose) give rise to rhythms in macronutrient metabolism, appetite regulation and the components of energy balance such that our bodies can align the periodic delivery of nutrients with ongoing metabolic requirements. The timing of meals both in absolute terms (i.e. relative to clock time) and in relative terms (i.e. relative to other daily events) is therefore relevant to metabolism and health. Experimental manipulation of feeding-fasting cycles can advance understanding of the effect of absolute and relative timing of meals on metabolism and health. Such studies have extended the overnight fast by regular breakfast omission and revealed that morning fasting can alter the metabolic response to subsequent meals later in the day, whilst also eliciting compensatory behavioural responses (i.e. reduced physical activity). Similarly, restricting energy intake via alternate-day fasting also has the potential to elicit a compensatory reduction in physical activity, and so can undermine weight-loss efforts (i.e. to preserve body fat stores). Interrupting the usual overnight fast (and therefore also the usual sleep cycle) by nocturnal feeding has also been examined and further research is needed to understand the importance of this period for either nutritional intervention or nutritional withdrawal. In summary, it is important for dietary guidelines for human health to consider nutrient timing (i.e. when we eat) alongside the conventional focus on nutrient quantity and nutrient quality (i.e. how much we eat and what we eat).</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1299-1312"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39827637","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":"Increasing SR Ca uptake: a double-edged sword.","authors":"Carlos A Valverde,&nbsp;Alicia Mattiazzi","doi":"10.1113/JP282659","DOIUrl":"https://doi.org/10.1113/JP282659","url":null,"abstract":"We read with great attention the recently published article by Sato et al. titled ‘Increasing SERCA function promotes initiation of calcium sparks and breakup of calcium waves’ (Sato et al. 2021). We believe that the opposing effects of increasing SR Ca uptake described in the paper is very significant, not only from the physiological point of view, but also because of the possible therapeutic consequences. It is very well known that different attempts have been made and are in course, to treat cardiac failure by improving SR Ca uptake and increasing systolic and diastolic function (Greenberg et al. 2014; Hulot et al. 2017; Lyon et al. 2020; Wasala et al. 2020). As is clear from Sato’s results, this constitutes a double-edged sword, because the increase in SR Ca content may also increase SR Ca leak and cardiac arrhythmias. However, if the increase in SR Ca uptake is high enough, SR Ca load and contractility may be improved, whereas SR Ca waves are aborted. Still, several questions remain to be discussed. One of them refers to the effects of a persistent and exacerbated increase in SR Ca leak. Although the increase in SR Ca uptake may be less arrhythmogenic because of Ca wave abortion, which is the consequence of the chronic exacerbated SR Ca leak? In our previous study (Mazzocchi et al. 2016), also published in the Journal of Physiology, we showed that phospholamban (PLN) ablation increased SR Ca leak but prevented arrhythmogenic Ca waves, by breaking them up into mini waves. Interestingly we also showed that decreasing SERCA2a activity by addition of CPA, reinstalled the previous arrhythmogenic full-calcium wave pattern, in complete agreement with Sato et al.’s results. We further showed that ablation of PLN was able to abort SR Ca waves observed in myocytes that, in addition to PLN ablation present an increase in RyR2 open probability produced by constitutive pseudo-phosphorylation of RyR2 at the CaMKII-dependent phosphorylation site Ser2814/15 (van Oort et al. 2010). These double mutant mice were named SDKO mice. In a following study (Valverde et al. 2019), we examined the role of PLN ablation on arrhythmogenic Ca waves in hearts submitted to a protocol of ischaemia/reperfusion. Under these conditions, we had the chance to investigate the effects that the increased SR Ca leak produced by PLN ablation, both in the presence and absence of RyR2 pseudo-phosphorylation at the Ser2814 site. The results indicated that, although able to reduce arrhythmogenic Ca waves, even when SR Ca leak was greatly enhanced in SDKO hearts, ablation of PLN altered mitochondria function and exacerbates cardiac damage. These results fully agree with earlier experiments by Joan Heller Brown and Don Bers ́ groups (Zhang et al. 2010), in which it was shown that ablation of PLN exacerbated cardiac damage in CaMKII-overexpressing mice, with enhanced phosphorylation of the Ser2814 site. Although, Sato et al. (2021), did not mention or discuss neither our results nor Bers and","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1533-1534"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912249","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":"Selective stimulation with intraneural electrodes for bionic limb prostheses can contribute to shed light on human touch sensorimotor integration.","authors":"Calogero Maria Oddo","doi":"10.1113/JP282734","DOIUrl":"https://doi.org/10.1113/JP282734","url":null,"abstract":"Stimulus delivery is a major challenge in the investigation of sensory physiology and physiopathology, with translational implications while targeting bionic substitution of impaired sensorimotor functions by means of neuroprostheses. The complexity represented by stimulus administration is generally valid for all senses, and particularly for touch among physical senses because of the distributed positioning of receptors throughout the large area of the whole skin and the intrinsically interactive characteristics of somatosensation. In touch studies, the experimental protocols typically involve the delivery of mechanothermal or electrical stimuli and the collection and analysis of stimulus-induced responses, either at perceptual level bymeans of psychophysical methods or by investigating peripheral or central bioelectronic activity in humans or animals via techniques such as microneurography and microstimulation, patch clamp, electrode arrays, functional magnetic resonance imaging, or electroencephalography. When the stimulus is delivered mechanically directly to the epidermis of intact subjects, such as with vibrotactile probes, extended textures or shapes, the spatiotemporal interaction with the skin should be carefully controlled over multiple sessions, for example by using custom biorobotic tools. Such automatic mechatronic platforms should be developed to allow gathering of repeatable responses of the somatosensory pathways in order to enable modelling attempts based on brain imaging or electrophysiological recordings at higher stages with respect to the cutaneous haptic stimulation site. Another suitable approach involves accessing directly the nervous system in order to release electrical pulses to the afferent pathways. The electrical delivery of the stimuli is extremely challenging because of the complexity of guaranteeing mechanical, electrical and biological stability of the electrode-nerve interface, the high number of stimulation sites, and selectivity, both spatially and temporally. Among the possible methods for releasing electrical patterns to the nervous system, microstimulation with needle electrodes is a technique used by trained neurophysiologists for eliciting action potentials with excellent axonal selectivity within a microneurographic session (Vallbo, 2018). While being minimally invasive, and thus applicable in trials involving either intact or amputee humans, microstimulation has the inherent constraint of single-site electrode placement and stability limited to short term protocols in acute subjects. However, progress with neurotechnologies and neurosurgical techniques has enabled over the past decade a series of studies that are demonstrating the feasibility of chronically implanting electrodes in the peripheral nerves of human subjects for neuroprosthetic applications, such as perineural cuffs or intraneural filament electrodes that are being applied in pilot clinical trials with limb amputees to partially restore sen","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1279-1280"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39694212","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":"GLOBAL REACH 2018: intra-arterial vitamin C improves endothelial-dependent vasodilatory function in humans at high altitude.","authors":"Rachel M Stone,&nbsp;Philip N Ainslie,&nbsp;Joshua C Tremblay,&nbsp;John D Akins,&nbsp;David B MacLeod,&nbsp;Michael M Tymko,&nbsp;Christopher A DeSouza,&nbsp;Anthony R Bain","doi":"10.1113/JP282281","DOIUrl":"https://doi.org/10.1113/JP282281","url":null,"abstract":"<p><p>High altitude-induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude. Ten young healthy lowlanders were tested at sea level (344 m) and following 4-6 days at high altitude (4300 m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain-gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP) and a co-infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high altitude than at sea level (P = 0.048). There was no difference in the response to SNP at high altitude (P = 0.860). At sea level, the co-infusion of ACh+VitC had no influence on the FBF dose response (P = 0.268); however, at high altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% (P = 0.019). At high altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxaemia (R² = 0.60, P = 0.008 and R² = 0.63, P = 0.006, respectively). Collectively, these data support the hypothesis that impairments in vascular endothelial function at high altitude are in part attributable to oxidative stress, a consequence of the magnitude of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related vascular dysfunction. KEY POINTS: Vascular dysfunction has been demonstrated in lowlanders at high altitude (>4000 m). However, the extent of impairment and the delineation of contributing mechanisms have remained unclear. Using the gold-standard isolated perfused forearm model, we determined the extent of vasodilatory dysfunction and oxidative stress as a contributing mechanism in healthy lowlanders before and 4-6 days after rapid ascent to 4300 m. The total forearm blood flow response to acetylcholine at high altitude was decreased by ∼30%. Co-infusion of acetylcholine with the antioxidant vitamin C partially restored the total forearm blood flow by ∼20%. The magnitude of forearm blood flow reduction, as well as the impact of oxidative stress, was positively associated with the individual severity of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related changes in endothelial-mediated vasodilatory function.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1373-1383"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39684896","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":"Altered muscle mitochondrial, inflammatory and trophic markers, and reduced exercise training adaptations in type 1 diabetes.","authors":"Dean Minnock,&nbsp;Giosuè Annibalini,&nbsp;Giacomo Valli,&nbsp;Roberta Saltarelli,&nbsp;Mauricio Krause,&nbsp;Elena Barbieri,&nbsp;Giuseppe De Vito","doi":"10.1113/JP282433","DOIUrl":"https://doi.org/10.1113/JP282433","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Growing evidence of impaired skeletal muscle health in people with type 1 diabetes points toward the presence of a mild myopathy in this population. However, this myopathic condition is not yet well characterised and often overlooked, even though it might affect the whole-body glucose homeostasis and the development of comorbidities. This study aimed to compare skeletal muscle adaptations and changes in glycaemic control after 12 weeks of combined resistance and aerobic (COMB) training between people with type 1 diabetes and healthy controls, and to determine whether the impaired muscle health in type 1 diabetes can affect the exercise-induced adaptations. The COMB training intervention increased aerobic capacity and muscle strength in both healthy and type 1 diabetes sedentary participants, although these improvements were higher in the control group. Better glucose control, reduced glycaemic fluctuations and fewer hypoglycaemic events were recorded at post- compared to pre-intervention in type 1 diabetes. Analysis of muscle biopsies showed an alteration of muscle markers of mitochondrial functions, inflammation, ageing and growth/atrophy compared to the control group. These muscular molecular differences were only partially modified by the COMB training and might explain the reduced exercise adaptation observed in type 1 diabetes. In brief, type 1 diabetes impairs many aspects of skeletal muscle health and might affect the exercise-induced adaptations. Defining the magnitude of diabetic myopathy and the effect of exercise, including longer duration of the intervention, will drive the development of strategies to maximise muscle health in the type 1 diabetes population. KEY POINTS: Type 1 diabetes negatively affects skeletal muscle health; however, the effect of structured exercise training on markers of mitochondrial function, inflammation and regeneration is not known. Even though participants with type 1 diabetes and healthy control were comparable for cardiorespiratory fitness ( &lt;math&gt;&lt;semantics&gt;&lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt;&lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;O&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;mi&gt;max&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;annotation&gt;${dot{V}_{{{rm{O}}_{rm{2}}}{rm{max}}}}$&lt;/annotation&gt;&lt;/semantics&gt;&lt;/math&gt; ) and muscle strength at baseline, molecular markers related to muscle health were decreased in type 1 diabetes. After training, both groups increased &lt;math&gt;&lt;semantics&gt;&lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt;&lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;O&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;mi&gt;max&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;annotation&gt;${dot{V}_{{{rm{O}}_{rm{2}}}{rm{max}}}}$&lt;/annotation&gt;&lt;/semantics&gt;&lt;/math&gt; and muscle strength; however, a larger improvement was achieved by the control group. The training intervention decreased glucose fluctuations and occurrence of hypoglycaemic events in type 1 diabetes, while signs of mild myopathy found in the muscle of participants with type 1 diabetes only partially improved after training Improving muscle health by specific exercise protocols is of considerable clinical ","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1405-1418"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39793678","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":"The end of an era.","authors":"Kim E Barrett","doi":"10.1113/JP282905","DOIUrl":"https://doi.org/10.1113/JP282905","url":null,"abstract":"","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1267-1268"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39606929","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":"Current research: effect of time restricted eating on weight and cardiometabolic health.","authors":"Kelsey Gabel,&nbsp;Krista A Varady","doi":"10.1113/JP280542","DOIUrl":"https://doi.org/10.1113/JP280542","url":null,"abstract":"<p><p>Intermittent fasting has grown in popularity as a weight loss strategy in recent years. In particular, time restricted eating (TRE) has been popularized in the diet industry with dozens of books touting its ability to promote weight loss and improve glucose regulation. TRE involves confining the eating window to a specified number of hours per day (usually 4-10 h), and fasting (with zero-calorie beverages) for the remaining hours of the day. While several studies of TRE have been performed in rodent models, human studies are only now emerging. The goal of this review is to summarize the effects of TRE on body weight and cardiometabolic disease risk factors in human subjects. Accumulating evidence shows that TRE may spontaneously decrease energy intake by 20-30% under ad libitum conditions, producing small but statistically significant weight loss of 1-4%. In addition, TRE may significantly decrease systolic and diastolic blood pressure independent of weight loss. Further, improvements in fasting insulin and insulin resistance have also been reported. Taken together, these preliminary data suggest that TRE produces mild weight loss, and also may improve some aspects of cardiometabolic health by lowering blood pressure and insulin resistance.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"1313-1326"},"PeriodicalIF":5.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1113/JP280542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38538508","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":"Pulmonary hypertension associated with chronic hypoxia: just ASIC-ness?","authors":"Philip I Aaronson","doi":"10.1113/JP282325","DOIUrl":"https://doi.org/10.1113/JP282325","url":null,"abstract":"Chronic hypoxia (CH) associated with lung diseases such as chronic obstructive pulmonary disease often results in structural and functional changes in the pulmonary vasculature leading to pulmonary hypertension (PH). Studies in animal models have revealed that CH induces PH by causing an array of changes in the phenotype of pulmonary artery (PA) endothelial and smooth muscle cells (PASMCs) which promote arterial remodelling and vasoconstriction. One of these, an increased cytosolic [Ca2+] in PASMCs, is at least partly due to enhanced Ca2+ influx through L-type voltage-gated Ca2+ channels resulting from a depolarization of the resting membrane potential (Em), which has long been ascribed to the decreased expression and activity of voltage-gated K+ (KV) channels. The rise in PASMC [Ca2+]cyt is also associated with increased expression of TRPC6 and TRPV4 channels, which mediate vasoconstrictor-induced Ca2+ influx, and of STIM/Orai and TRPC1 channels, which cause store-operated Ca2+ entry (SOCE) (Reyes et al. 2018). Nikki Jernigan and colleagues at the University of New Mexico School of Medicine in Albuquerque have previously demonstrated that CH also acts on PASMC to promote the membrane localization and increased activity of ASIC1a, one of a family of homoor heterotrimeric acid-sensing ion channels formed from subunits encoded by four genes (ASIC1–4). ASICs are non-selective cation channels (NSCCs) which are gated by extracellular protons. Nitta et al. (2014) reported that activation of ASIC1a contributes to the increased SOCE and receptor-mediated Ca2+ influx evoked by CH in PASMCs. This is possible because some ASICs, including ASIC1a homomers and ASIC1a/2b heteromers are Ca2+-permeable. Since ASIC1 is a NSCC, it can be predicted that its increased activity should additionally cause Na+ influx and membrane depolarization. In an article in the current issue of The Journal of Physiology, Jernigan et al. (2021) report that enhanced ASIC1a activity does indeed contribute significantly to CH-induced PASMC depolarization. The authors used whole cell patch clamping to evaluate the contribution of ASIC1 to the NSCCs present in freshly dispersed PASMCs from rats and mice exposed to normoxia or sustained hypobaric hypoxia (CH) for 4 weeks. They also measured Em in isolated small PAs, which were cannulated to allow measurement of Em at different levels of internal pressure. As previously reported by many labs, the authors observed that the KV current was smaller in PASMCs from CH animals. In the absence of K+ and extracellular Ca2+, with Na+ and Cs+ as the predominant extracellular and intracellular cations, respectively, they observed a small quasi-linear non-inactivating currentwhich reversed at 0 mV. The current density was markedly increased by CH. This current was unaffected by Cl– channel antagonists but was greatly diminished by removal of extracellular Na+, especially in the CH cells, indicating that it was due to one or more types of NSCC. Applying","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4731-4732"},"PeriodicalIF":5.5,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39428066","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}