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!
David C.R. Michels et al.
Beyond cancer: breast cancer gene 2 emerges as a new player in atherosclerosis
Atherosclerosis is a chronic immunoinflammatory disease driven by endothelial dysfunction, oxidative stress, and DNA damage. Although breast cancer gene 2 (BRCA2) is a key regulator of homologous recombination-mediated DNA damage repair, its role in vascular biology remains unclear.
NEW & NOTEWORTHY
This study uncovers a novel role for endothelial BRCA2 in limiting atherosclerosis. Endothelial cell-specific loss of BRCA2 is dispensable at baseline, but under high-fat diet stress, it significantly worsens atherosclerosis and causes splenomegaly. BRCA2 also regulates pathways beyond DNA repair in endothelial cells. These findings identify a new potential therapeutic target for atherosclerosis and suggest that individuals with BRCA2 mutations may have increased cardiovascular risk, expanding the known impact of BRCA2 beyond cancer susceptibility.
Ronghao Zhang et al
NEW & NOTEWORTHY
This study identifies abnormal mineralocorticoid receptor (MR) activation as a driver of fructose-induced salt-sensitive hypertension. Despite unchanged serum aldosterone levels, increased renal 11β-HSD1 suggests MR activation by glucocorticoids. The blood pressure increase caused by fructose and salt was reversed by MR blockade with eplerenone and ENaC inhibition with amiloride. These findings reveal a novel mechanism linking fructose consumption to abnormal distal nephron regulation, providing new insights into the pathogenesis of diet-induced hypertension.
Jordan A. Rhymes et al.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that occurs more frequently in women and is associated with an increased risk of renal injury and hypertension. Studies have shown that obesity is associated with greater SLE disease activity and is a significant modifiable risk factor for hypertension
NEW & NOTEWORTHY
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that primarily affects women and is associated with high rates of hypertension and obesity. This study tested the hypothesis that caloric restriction would decrease disease activity and lower blood pressure in the NZBWF1 mouse, an obese and hypertensive model of SLE. Caloric restriction mice had decreased SLE disease activity, with lower anti-dsDNA IgG autoantibodies, albuminuria, renal B and T cell infiltration, and blood pressure.
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 Hirohito Kuno et al in Cell Reports: Intralaminar thalamus relays basal ganglia output to the insular cortex to drive tic generation
Significance
The authors have demonstrated that the basal ganglia-intralaminar thalamo-insular pathway plays an important role in the generation of tics, using a mouse model that exhibits prominent tic-like movements. Tic disorders are characterized by sudden, repetitive movements (“motor tics”) and vocalizations including inappropriate words or sounds (“vocal tics”). Many patients experience unpleasant sensations that precede tics, known as premonitory urges, and frequently have comorbid psychiatric conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). These clinical features suggest that tic disorders arise from dysfunction beyond motor brain regions. Instead, brain areas involved in uncomfortable internal sensations and emotional processing may also contribute to the pathophysiology of tics. However, the underlying neuronal mechanisms have remained unclear.
Our study revealed that the intralaminar thalamic nuclei connect motor domains of the basal ganglia to the insular cortex, a brain region involved in sensory and emotional processing. We further showed that chemogenetic inhibition of the intralaminar thalamo-insular pathway in the tic mouse model reduced tic-like movements and abnormal neuronal activities associated with tics. These findings provide new insight into the neuronal mechanisms underlying tic disorders and can contribute to the future development of novel therapeutic strategies
DPG’s latest paper of the month (D Derstroff et al) was recently published in Neuron
TMEM145 is a principal component of outer hair cell stereocilia
From the abstract:The exquisite acuity of mammalian hearing relies on cochlear amplification provided by sensory outer hair cells (OHCs), downstream of mechanoelectrical transduction of sound. In OHCs, transduction is initiated by deflection of stereocilia conveyed through tethering to the tectorial membrane (TM) via an incompletely characterized protein complex, the TM attachment crowns (TM-ACs). We identify Tmem145, a G protein-coupled receptor (GPCR)-related “Golgi-dynamics-domain-seven-transmembrane (GOST)” protein, as the core element of TM-ACs. Tmem145 localized to the tips of the tallest row of stereocilia, precisely matching the localization of previously known components of TM-ACs, tubby, and stereocilin. Genetic ablation in mice resulted in loss of tubby and stereocilin from OHC stereocilia, disconnection of the hair bundle from the TM, and profound hearing loss with a lack of cochlear amplification. Tmem145 binds cytosolic tubby and anchors secreted stereocilin, likely through its extracellular Golgi-like domain. This architecture suggests a general role of Tmem145-related proteins as organizers of transmembrane anchor complexes.