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!
Jacob A. Herring et al.
From the abstract: Functional β-cell mass is the combination of the β-cell’s ability to secrete insulin, proliferate, and survive under damaging stress. The Nr4a family of transcription factors controls the expression of genes essential for fuel metabolism and cellular proliferation. We report the effects of β-cell specific Nr4a1 deletion in mice (Nr4a1β−/−). We determined that Nr4a1β−/− impairs glucose tolerance in female mice fed a high-fat diet. We found decreases in β-cell mass and glucose-stimulated insulin secretion. Nr4a1β−/− decreased mRNA and protein levels of key genes involved in glucose utilization and cell cycle progression. Estrogen treatment induces mRNA and protein expression of Nr4a1 in cell lines as well as primary mouse islets.
Jennifer C. Pryor et al.
From the publication: A growing proportion of the non-celiac population experiences adverse symptoms to gluten. The pathogenesis of non-celiac gluten sensitivity (NCGS) is unclear, but elevated duodenal eosinophils and altered mucosa-associated microbiota (MAM) populations have been reported. A mouse model examined how microbial modulation affects immune responses to gluten. Antibiotic treatment followed by gluten reintroduction reduced duodenal Staphylococcus and altered microbial carbohydrate and lipid metabolism pathways in the fecal microbiome. Antibiotics and gluten treatment resulted in increased abundance and activation of duodenal eosinophils and elevated γδ T-cells in the duodenal epithelium. These findings highlight the role the microbiome plays in gluten-induced immune responses, providing insights into mechanisms behind non-celiac gluten sensitivity.
Eden M. Gallegos et al.
From the abstract: Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease frequently co-occur, manifesting as MetALD. Understanding the hepatocyte-specific effects of alcohol and metabolic stressors is critical to uncovering mechanisms of synergistic injury. Ethanol and metabolic stressors synergize to dysregulate hepatocyte lipid homeostasis and oxidative stress while additively impairing mitochondrial bioenergetics. Gene expression results suggest that lipid accumulation may be driven by altered expression of triglyceride storage and lipid handling markers rather than de novo lipogenesis. These findings highlight the importance of metabolic contributions in alcohol-induced hepatocellular dysfunction and establish HepaRG spheroids as a robust model to elucidate hepatocyte-specific responses in MetALD.
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 (Karen Lahme et al) was recently published in Cell.
From the abstract: Chronic kidney disease affects 1 in 10 people worldwide, with damage to specialized blood filter cells of the kidney, called podocytes, playing a critical role. In membranous nephropathy (MN), a major cause of nephrotic syndrome, circulating autoantibodies attack proteins on podocyte foot processes (FPs), damaging the kidney’s filtration barrier. This study shows that these autoantibodies trigger the formation of antigen-autoantibody aggregates on the podocyte FP plasma membrane. These aggregates bud off as stalked vesicles, termed autoimmunoglobulin-triggered extracellular vesicles (AIT-EVs), which are released into the urine. AIT-EVs carry disease-causing autoantibodies, their target antigens, essential FP proteins, and disease-associated stressors representing a mechanism for removing immune complexes (ICs) and waste. However, their excessive release leads to FP effacement and podocyte dysfunction. In MN patients, urinary AIT-EVs correspond to glomerular urinary-space aggregates. Enriching AIT-EVs enables detection and monitoring of pathogenic autoantibodies, suggesting a non-invasive approach for autoimmune kidney disease diagnosis and therapy.