To study brain‐sparing physiological responses in a rodent model of birth asphyxia which reproduces the asphyxia‐defining systemic hypoxia and hypercapnia.

Within the current paradigm of the myonuclear domain theory, it is postulated that a linear relationship exists between muscle fibre size and myonuclear content. The myonuclear domain is kept (relatively) constant by adding additional nuclei (supplied by muscle satellite cells) during muscle fibre hypertrophy and nuclear loss (by apoptosis) during muscle fibre atrophy. However, data from recent animal

When low‐altitude people rapidly ascend to altitudes above 2500 m, they run a risk of developing high‐altitude pulmonary edema (HAPE)1. The first scientific report in an English‐written journal was published in 19602, and still in 1975 the article by Kleiner and Nelson in JAMA had a title: High‐altitude pulmonary edema: A rare disease?3 However, as tourism at high altitudes has become common and as

We aimed to assess the ability of natural and modified polyunsaturated fatty acids to shorten QT interval in ex‐vivo and in‐vivo guinea pig hearts.

The new coronavirus, classified as SARS‐CoV‐2 that emerged in Hubei province in China, causes a new coronavirus disease, which was termed COVID‐19 by WHO on February 11, 2020. COVID‐19 claimed almost 19000 lives around the world by March 25, 2020

We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID‐19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 manifests as dry cough, frequent fevers and in severe cases pneumonia. Older patients and patients with underlying

It is debated whether the inhibition of glucagon secretion by glucose results from direct effects of glucose on the α‐cell (intrinsic regulation) or by paracrine effects exerted by beta‐ or delta‐cell products.

Sir George W. Pickering was an astute, opinionated observer and highly gifted cardiovascular investigator. He considered the rich history of cardiovascular research, settled on the term “essential hypertension” (although he did not like it much), and left us with two challenges and then outlined three areas of investigation, namely animal models, human translational studies, and genetics to pursue

AIMS The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2 peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra-physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity

AIM Interventions that decrease atrophy during disuse are desperately needed to maintain muscle mass. We recently found that massage as a mechanotherapy can improve muscle regrowth following disuse atrophy. Therefore, we aimed to determine if massage has similar anabolic effects when applied during normal weight bearing conditions (WB) or during atrophy induced by hindlimb suspension (HS) in adult

AIM High altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that can occur during rapid ascent to a high-altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary edema rather than as a causative factor

The mitochondrial GTPase, OPA1 (Optic Atrophy 1) plays a major role in mitochondrial structure and function, regulating both the fusion of membranes and cristae ultrastructure 1. OPA1 is associated with a wide range of pathologies in which mitochondrial dysfunction occurs, including neurodegenerative and cardiac diseases, as well as primary mitochondrial diseases such as dominant optic atrophy, Behr

Diabetes mellitus had a global prevalence of 8.5 % in 2014; in other words 422 million people were affected. This chronic metabolic disease is not only common in wealthy countries, but it is also rising in those of middle and low income. The World Health Organization (WHO) declared diabetes as one of the leading causes of death in the world.

Sleep disordered breathing (SDB) is a common obesity-related co-morbidity with strong associations to cardiometabolic disease. The risk of SDB is increased during pregnancy, particularly amongst obese pregnant women. Accumulating evidence suggests that an association exists between maternal SDB and the development of adverse pregnancy outcomes, particularly gestational diabetes and hypertensive disorders

AIM Arginase 2 (ARG2) is a mitochondrial enzyme that catalyzes hydrolysis of L-arginine into urea and L-ornithine. In the kidney, ARG2 is localized to the S3 segment of the proximal tubule. It has been shown that expression and activity of this enzyme are upregulated in a variety of renal pathologies, including ischemia-reperfusion (IR) injury. However, the (patho)physiological role of ARG2 in the

Would beauty come with impact factors, the queen’s vain enquiry would probably have remained unanswered. Nonetheless, when it comes to physiology journals, we cannot resist asking the mirror, which of our periodicals is best.[2, 3] Yet, all attempts remain futile.

AIM During pregnancy, the maternal β-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent β-cell attachment and proliferation in vitro. The aim of this study was to identify adhesion molecules involved in expansion of the β-cell mass during pregnancy in the rat. METHODS Quantitative RT-PCR was used to evaluate the expression of

The voltage-gated sodium (NaV ) channel is required for cardiomyocyte function. In heart, its major, pore-forming, α-subunit is NaV 1.5, encoded by SCN5A, which maps to chromosome 3p21. The NaV channel plays a key role in myocardial excitability, since it is responsible for generating the rising phase of the cardiac action potential. NaV 1.5 often shows alterations in inherited channelopathies causing

AIM Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high-fat diet-induced increases in circulating lipids on microvascular remodelling are not established. Here

How to best measure journal performance remains a controversial issue. Routinely, the impact factor of the journal is taken, although this measure was never designed to reflect journal performance. The impact factor was developed as a tool for librarians in academia to sort out, which of the many very different journals may best suit the demands of their readers. As the annual impact factors are released

Computational models have made a major contribution to the field of physiology. As the complexity of our understanding of biological systems expands, the need for computational methods only increases. But collaboration between experimental physiologists and computational modellers (ie theoretical physiologists) is not easy. One of the major challenges is to break down the barriers created by differences

The annual Winter School of the Danish Diabetes Academy (DDA) in November 2019 challenged postdoctoral researchers with tough questions regarding research culture that scientists around the world are discussing. The complexity and competitiveness of modern research makes it increasingly difficult for junior researchers to navigate in the science community. This editorial reflects the voices of nearly

Cellular plasticity is a topical subject with interest spanning a wide range of fields from developmental biology to regenerative medicine. Even the nomenclature is a subject of debate, and the underlying mechanisms are still under investigation. On top of injury repair, cell plasticity is a constant physiological process in adult organisms and tissues, in response to homeostatic challenges. In this

AIM Sexual dimorphisms are evident along the nephron: Females (F) exhibit higher ratios of renal distal to proximal Na+ transporters' abundance, greater lithium clearance (CLi ) more rapid natriuresis in response to saline infusion and lower plasma [K+ ] vs. males (M). During angiotensin II infusion hypertension (AngII-HTN) M exhibit distal Na+ transporter activation, lower proximal and medullary loop

Much has been written on how various issues unrelated to science can affect acceptance or rejection of your manuscripts, for instance in Acta Physiologica.[1, 2] For many, journal rankings are becoming a matter of feast or famine as national funding agencies assess scientific output to efficiently distribute their limited resources. Yet, how do agencies objectively value scientific output? There are

Most organisms evolved endogenous, so called circadian clocks as internal timekeeping mechanisms allowing them to adapt to recurring changes in environmental demands brought about by 24-hour rhythms such as the light-dark cycle, temperature variations or changes in humidity. The mammalian circadian clock system is based on cellular oscillators found in all tissues of the body that are organized in

We thank Sandal et al. for taking an interest in our paper1 and the intriguing question on the determinants of mean arterial blood pressure (MAP) in mammals. Sandal et al. 2present a correlation between MAP and the vertical distance between the heart and the brain in 16 different species of (predominantly large) mammals.

Obesity and obesity‐related diseases have turned into a major global health risk. This is no longer restricted to highly developed countries [1] and has reached epidemic degrees in many regions. A diversity of metabolic and inflammatory pathophysiological phenotypes can be related to obesity, which represent a burden for healthcare and insurance systems, but particularly to affected people.

AIM Cardiovascular complications, including cardiac arrhythmias, result in high morbidity and mortality in patients with type-2 diabetes mellitus (T2DM). Clinical and experimental data suggest electrophysiological impairment of the natural pacemaker of the diabetic heart. The present study examined sinoatrial node (SAN) arrhythmias in a mouse model of T2DM and physiologically probed their underlying

AIM The cAMP-mediator Epac1 (RapGef3) has high renal expression. Preliminary observations revealed increased diuresis in Epac1-/- mice. We hypothesized that Epac1 could restrict diuresis by promoting transcellular collecting duct (CD) water and urea transport or by stabilizing CD paracellular junctions to reduce osmolyte loss from the renal papillary interstitium. METHODS In Epac1-/- and Wt C57BL/6J

Nitric oxide (NO), a highly reactive gasotransmitter, is critical for a number of cellular processes and has multiple biological functions. Due to its limited lifetime and diffusion distance, NO has been mainly believed to act in autocrine/paracrine fashion. The increasingly recognized effects of pharmacologically delivered and endogenous NO at a distant site have changed the conventional wisdom and

AIM Imbalanced mitochondrial dynamic including suppressed mitochondrial fusion has been observed in diabetic hearts. However, it is still unknown whether mitochondrial fusion promoter is an effective protection to diabetic hearts. This study was designed to explore the efficacy of mitochondrial fusion promoter on diabetic cardiomyopathy (DCM). METHODS Male Sprague-Dawley rats were injected with streptozotocin

AIMS Pathogenic variants of the SCN5A gene can cause Brugada syndrome (BrS) and long QT syndrome (LQTS), which predispose individuals to potentially fatal ventricular arrhythmias and sudden cardiac death. SCN5A encodes the NaV 1.5 protein, the pore forming α-subunit of the voltage-dependent cardiac Na+ channel. Using a WW domain, the E3 ubiquitin ligase Nedd4-2 binds to the PY-motif ([L/P]PxY) within

AIMS Burrowing mammals tend to be more hypoxia tolerant than non-burrowing mammals and rely less on increases in ventilation and more on decreases in metabolic rate to tolerate hypoxia. Naked mole-rats (Heterocephalus glaber, NMRs), eusocial mammals that live in large colonies, are among the most hypoxia-tolerant mammals, and rely almost solely on decreases in metabolism with little change in ventilation

AIM To explore the role of the histidine triad nucleotide-binding 2 (HINT2) protein in heart failure. METHODS Neonatal mouse ventricle myocytes (NMVMs) and myocardial infarction-induced heart failure mice were used for in vitro or in vivo experiments. Adenovirus (ADV) and adeno-associated virus serum type 9 (AAV9) vectors were used to regulate HINT2 expression. The expression of HINT2 was determined

Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective

The ancient Greek god Asclepius and his serpent‐entwined rod are well known among physicians and still associated with present‐day medicine and health care 1. Different origins and meanings are attributed to the snake rod symbol, and of particular significance is the belief that the snake symbol expresses the dual nature of the work of the physician, e.g. in the context of therapeutic drug use.

AIM Astroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the role of these proteins in response to currently available

AIM Neurons in the arcuate nucleus of the hypothalamus are involved in regulation of food intake and energy expenditure, and dysregulation of signalling in these neurons promotes development of obesity. The role of the rate-limiting enzyme in the NAD+ salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), for regulation energy homeostasis by the hypothalamus has not been extensively studied

Weightlessness in space induces a fluid shift from the dependent to the cephalad parts of the body leading to distension of the cardiac chambers and an accumulation of blood in the veins of the head and neck. Surprisingly, central venous pressure (CVP) during the initial hours of spaceflight decreases compared to being horizontal supine on the ground. The explanation is that the thorax is expanded

In the current issue of Acta Physiologica, Larsson and colleagues examined the effect of chaperone co‐inducer BGP‐15 on impaired contractile function of the slow‐twitch soleus muscles in a rat intensive care unit (ICU) model.1 They found that BGP‐15 improves myofibrillar function in the soleus muscle after 5 days exposure to the ICU condition, which is accompanied by improved mitochondrial morphology/biogenesis

AIM The loss of insulin-secreting β-cells, ultimately characterizing most diabetes forms, demands the development of cell replacement therapies. The common endpoint for all ex vivo strategies is transplantation into diabetic patients. However, the effects of hyperglycaemia environment on the transplanted cells were not yet properly assessed. Thus, the main goal of this study was to characterize global

Obesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function

Prolonged unloading of skeletal muscle, a common outcome of events such as spaceflight, bed rest and hindlimb unloading, can result in extensive metabolic, structural and functional changes in muscle fibres. With advancement in investigations of cellular and molecular mechanisms, understanding of disuse muscle atrophy has significantly increased. However, substantial gaps exist in our understanding

Heart failure (HF) is the end-stage syndrome for most cardiac diseases, and the 5-year morbidity and mortality of HF remain high. Malignant arrhythmia is the main cause of sudden death in the progression of HF. Recently, bridging integrator 1 (BIN1) was discovered as a regulator of transverse tubule function and calcium signalling in cardiomyocytes. BIN1 downregulation is linked to abnormal cardiac

AIM Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co-inducer BGP-15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive

There is a great interest in exploring the mechanisms of oedema in nephrotic syndrome (NS) as evidenced by 2 parallel studies published in Acta Physiologica (1, 2). This has generated an editorial comment (3) which we respond to by this rebuttal. The interest in the nephrotic edema reflects not only the significant negative impact this has on the quality of life, but also the difficulties associated

AIM It is widely accepted that the exocytosis of synaptic and secretory vesicles is triggered by Ca2+ entry through voltage-dependent Ca2+ channels. However, there is evidence of an alternative mode of exocytosis induced by membrane depolarization but lacking Ca2+ current and intracellular Ca2+ increase. In this work we investigated if such a mechanism contributes to secretory vesicle exocytosis in

In a letter to the editor by Figureiredo et al1, entitled “On the appropriateness of antibody selection to estimate mTORC1 activity”, the authors question our choice of mTORC1 biomarkers2. We much appreciate the input and the possibility to emphasize our conclusions.

We welcome the opportunity to reply to the elegant editorial of Prof. Ehmke 1 in which he highlights contradicting conclusions reached by Hinrichs et al. 2 and by us 3 in two recently published articles in Acta Physiologica. In our reply, we first comment on some technical aspects discussed by Prof. Ehmke as possible explanations for the discrepant conclusions reached in the two studies. In addition

Humans are obligate aerobic organisms that need air for life. The utmost importance of air for life has already been recognized thousands of years ago and is still evident in aspects of the ancient Greek medicine where blood was the humor associated with air. However, only a fraction, namely the ~20% of oxygen, constitutes the vital part from the air that we breeze. In the cell, oxygen is required

AIM Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals. METHODS Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high-fat/high-sucrose

AIM Type 2 diabetes and obesity are diseases related to surplus energy in the body. Abnormal interaction between the hypothalamus and adipose tissues is a key trigger of energy metabolism dysfunction. Extracellular vesicles (EVs) regulate intercellular communication by transporting intracellular cargo to recipient cells thereby altering the function of recipient cells. This study aimed to evaluate

AIM Cardiac hypertrophy and myocardial apoptosis are two major factors in heart failure. As a classical regulator of apoptosis, apoptosis repressor with caspase recruitment domain (ARC) has recently also been found to have a protective effect against hypertrophy. However, the mechanism underlying this effect is still not fully understood. METHODS In the present study, we established animal and cellular

AIM Claudin-15 is mainly expressed in the small intestine and indirectly involved in glucose absorption. Similar to claudin-2 and -10b, claudin-15 is known to form a paracellular channel for small cations. Claudin-2, but not claudin-10b, also forms water channels. Here we experimentally tested whether claudin-15 also mediates water transport and if yes, whether water transport is Na+ -coupled, as seen

The most important task of the olfactory system is to generate a precise representation of odour information under different brain and behavioural states. As the first processing stage in the olfactory system and a crucial hub, the olfactory bulb plays a key role in the neural representation of odours, encoding odour identity, intensity and timing. Although the neural circuits and coding strategies

P‐glycoprotein (Pgp/MDR1) plays a major role in intestinal homeostasis. Decrease in Pgp function and expression has been implicated in the pathogenesis of IBD. However, inhibitory mechanisms involved in the decrease of Pgp in inflammation are not fully understood. Angiotensin II (Ang II), a peptide hormone predominantly expressed in the epithelial cells of the crypt‐villus junction of the intestine

AIM Protein kinase (PK) A anchoring protein (AKAP) 12 is a scaffolding protein that anchors PKA to compartmentalize cyclic AMP signalling. This study assessed the consequences of the downregulation or deletion of AKAP12 on endothelial cell migration and angiogenesis. METHODS The consequences of siRNA-mediated downregulation AKAP12 were studied in primary cultures of human endothelial cells as well

Highly active cardiomyocytes need iron for their metabolic activity. In physiological conditions, iron turnover is a delicate process which is dependent on global iron supply and local autonomous regulatory mechanisms. Though less is known about the autonomous regulatory mechanisms, data suggest that these mechanisms can preserve cellular iron turnover even in the presence of systemic iron disturbance

Blood flow-restricted resistance exercise (BFRRE) has been shown to induce increases in muscle size and strength, and continues to generate interest from both clinical and basic research points of view. The low loads employed, typically 20%-50% of the one repetition maximum, make BFRRE an attractive training modality for individuals who may not tolerate high musculoskeletal forces (eg, selected clinical