Physiology is a wide spanning discipline, and it is interesting to follow its journey into the unknown in different organs, and with ever more sophisticated methods. This research is reflected by high quality publications in physiological journals. Have a look!
The results of this research as well as of comparative physiology and mathematical modelling, provide ever growing insight into the body’s functions, mechanisms of disease and new therapies, including gene therapy and development of vaccines. The close interaction between basic physiological research and clinical work, has improved human health and life span and holds even more promises for the future.
A most interesting aspect of current physiology is that, unlike in past centuries, novel models and techniques have reduced or replaced the need to destroy or dissect organs and tissues to improve understanding of function. Now we can learn from growing cells and stimulating them to form tissues and even “organs”. It has become almost routine for physiologists to manipulate gene expression to study function in the intact animal. We are obtaining novel and unique insights into the principles of self-organisation of cells and their mutual interactions. Exciting times, indeed!
Physiology is a wide spanning discipline, and it is interesting to follow its journey into the unknown in different organs, and with ever more sophisticated methods. This research is reflected by high quality publications in physiological journals. Have a look!
Stephen J Faulkes et al.
NEW & NOTEWORTHY This case study of a highly trained ultra-endurance athlete performing two world-record setting 12 and 24 h cycling bouts provides the most definitive illustration that a sufficiently intense and prolonged dose of exercise (in this case, 24 h of intense cycling) can result in acute heart failure. The absence of persistent myocardial injury highlights the remarkable resilience of the cardiovascular system to acute stress and reinforces the importance of adequate recovery following prolonged and intensive endurance exercise bouts.
Jennifer Nogueira-Coelho et al.
Empagliflozin targets a renal neuro-epithelial-immune axis in heart failure
NEW & NOTEWORTHY These findings identify a renal neuro-epithelial-immune axis that may, at least in part, underlie empagliflozin-mediated renoprotection in heart failure. Empagliflozin selectively attenuated surrogate markers of renal sympathetic activity, lowering cortical and urinary norepinephrine without detectable changes in intrarenal renin-angiotensin system components. These changes were accompanied by a shift toward a reparative macrophage phenotype. In vitro, empagliflozin blocked norepinephrine-induced SGLT2 upregulation and IL-6 production, linking sympathetic signaling to tubular inflammation.
et al.
Elevated Circulating Bile Acids Driven Erythrocyte Osmotic Resistance Marks Hepatobiliary Disease
NEW & NOTEWORTHY Elevated circulating bile acids are associated with increased red blood cell (RBC)
resistance to osmotic hemolysis in mice and humans. This phenotype reflects bile acid-driven
remodeling of RBC membranes and provides a basis for a whole-blood assay to assess cholemia
using small blood volumes.
Much more can be found in this month’s selection of articles from APS journals!
These new and engaging video feature from The Journal of Physiology aims to deliver short and informative research snapshots directly from the authors of research papers selected by the Editors of the journal!
You will find the “Science Topics” on the main page, scrolling down to “News” and clicking “Science Topics”.
The latest topic relates to an article published by Yoshifumi Takahata, Yuki Kasashima, Takuya Yoshioka et al in PNAS (A Period1 inducer specifically advances circadian clock in mice.)
Significance
The authors reveal that Mic-628 specifically and sufficiently induces Per1, provoking an abrupt phase advance in mouse behavioral rhythms, regardless of the timing of administration. Disruption of tandem E-boxes in the mPer1 promoter abolishes most of both mPer1 induction and phase-advancing activity, highlighting their role as unique binding sites for the CLOCK–BMAL1 complex. Mass spectrometry identified CRY1 as a potential target, with Mic-628 enhancing CRY1 binding to CLOCK-BMAL1, which tightly correlates with Per1 induction. Moreover, the autonomous PER1-mediated feedback repression likely explains the consistent phase-advancing profile. Overall, Mic-628 exerts its distinctive effect through precise molecular interactions that unveil an additional layer of transcriptional control within the circadian clock. This makes Mic-628 a promising therapeutic candidate for circadian disruptions.
PSJ celebrated its 100th anniversary in 2023. On this occasion the Journal of Physiology compiled a collection of some of the most influential research published by Japanese authors in this journal. Have a closer look here!
DPG’s latest paper of the month (Johanna K Freundt et al) was recently published in Nat Cardiovasc Res
Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis
From the abstract:Titin, the largest human protein, forms the elastic sarcomeric backbone, providing passive stiffness and length-dependent activation in cardiomyocytes. Whereas titin mutations cause inherited cardiomyopathies, ischemic and chemotherapy-induced injury also provoke proteolytic cleavage of titin’s elastic segment. However, the effects of acute titin stiffness loss remain unknown. Here we develop a knock-in mouse enabling in vivo cleavage of cardiac titin springs and use multimodal analysis (cardiac magnetic resonance imaging, echocardiography, microscopy, omics) to show that titin cleavage does not dilate the heart but reduces chamber size and impairs ventricular filling. Mechanical assays of isolated cardiomyocytes reveal diminished restoring forces causing a loss of elastic recoil. In vivo cleavage disrupts junctions, including integrin linkages and connexin 43 gap junctions, widens intermyocyte space without hypertrophy or hyperplasia and drives fibroblast activation, extracellular matrix remodeling and fibrosis. Compensatory mechanisms fail, leading to decompensated heart failure. These findings establish that proteolytic titin cleavage perturbs cardiac mechanical homeostasis, driving disease and matrix stiffening.