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!
Daniel G Spindola et al.
From the abstract: Sepsis survivors face a heightened risk of secondary infections following discharge, yet the underlying mechanisms remain poorly defined. This study identifies a novel mechanism of endothelial inflammatory memory, wherein inflammatory exposure induces durable chromatin remodeling in endothelial cells (ECs), priming them for exaggerated responses to a subsequent infection. This study provides an explanation why sepsis survivors face a heightened risk of secondary infections following discharge. Genome-wide ATAC-seq revealed that a subset of inflammatory gene loci in mouse endothelial cells retained increased chromatin accessibility even after cytokine withdrawal, demonstrating stable epigenetic remodeling consistent with transcriptional priming and inflammatory memory. In vitro, a critical role for the activator protein-1 transcription factor JunB in mediating this epigenetic remodeling was found. This discovery reveals a new mechanism of chronic endothelial dysfunction and identifies JunB as a potential therapeutic target in postsepsis care.
Suliana M Paula et al.
From the abstract: Gastroesophageal reflux disease (GERD) is defined as an effortless movement of stomach contents toward the esophagus. It may cause esophageal (recurrent and troublesome heartburn and regurgitation), supraesophageal symptoms, or complications (as peptic strictures and Barrett esophagus. Some forms of GERD are associated with crural diaphragm dysfunction, suggesting that GERD may be influenced by skeletal muscle deficiencies. Skeletal muscle atrophy has been strongly linked to alterations in the ubiquitin-proteasome system, the primary pathway for protein degradation. This study demonstrated, for the first time, an increased activation of the ubiquitin-proteasome pathway and elevated MuRF-1 expression in the crural diaphragm of humans with moderate reflux esophagitis. It showed a positive correlation between the supine reflux time and MuRF-1 expression, suggesting a molecular mechanism associated with diaphragm fiber atrophy and weakness. These findings highlight a potential link between diaphragm degradation and reflux esophagitis, which may modulate gastroesophageal reflux and symptoms.
Nathan T. Romberger et al.
Sex differences in central salt sensing in the human brain
From the abstract: In preclinical models, the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO) sense changes in serum sodium chloride (NaCl) concentration and mediate NaCl-induced changes in sympathetic nerve activity, vasopressin (AVP), thirst, and blood pressure (BP). In humans, brain imaging studies have shown that acute hypernatremia alters the activity or functional connectivity of the SFO and OVLT. However, no studies have investigated whether there are sex differences in central NaCl sensing in humans, which could underlie sex differences in neurohumoral responses to hypernatremia. e used resting-state fMRI to assess whether there are sex differences in the functional connectivity of salt sensing brain regions during acute hypernatremia in young healthy adults. Despite having similar increases in serum sodium, thirst, systolic BP, and plasma AVP, functional connectivity between the SFO and OVLT increased with acute hypernatremia in men but decreased in women when studied using resting-state fMRI . This suggests there may be sex differences in salt sensing in brain regions that regulate sympathoexcitation and BP.
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!
The latest topic relates to an article published by Shigetoshi Oiki
From the abstract : Single-molecule measurements of protein dynamics reveal discrete transitions between conformational states, providing critical kinetic information. However, recording signals often elicit flickering because rapid conformational transitions exceed the temporal recording resolution, making time-domain kinetic analysis challenging. We developed an amplitude-domain method to decipher the underlying rate of channel flickering. Experimental single-channel currents, when passed through a first-order filter, often yield two beta distributions (double-beta distributions) in the amplitude histogram. We revealed that these two components were projected from current traces comprising two aggregated Markov processes emerging alternatively (double-flicker gating). The underlying gating model of double flickering is related to the model topology, which exhibits mode switching. To estimate the underlying double-flickering rates, multiple amplitude histograms drawn from the filtered current data at different cut-off frequencies were simultaneously fitted with double-beta distributions. The simulated data for various models and rates verified the capability of the method for robust rate estimation.
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 (Constantin CE et al) was recently published in Nature communications.
The publication sheds a new light on the role of calcium ATPases in rapid clearing of intracellular calcium by extruding it from the cell. It is demonstrated that calcium ATPases consisting of PMCA2-NPTN complexes act as transporters with unanticipated high cycling rates which under cellular conditions may operate in the kHz-range.