Mosley et al. investigate the role of cytosolic DNA structure in activation of cGAS/STING by MSI colorectal cancers. They find MSI cytosolic DNA is enriched in G-quadruplexes, leading to more effective cGAS/STING activation. Micronuclei are less effective at activating cytotoxic T cells through cGAS/STING but increase IL-10 and Treg activation.
Marko et al. show that elevated insulin in obese mice suppresses adipocyte IRF4, which governs fat versus muscle preservation during 5:2 intermittent fasting (IF) with or without caloric restriction. During an acute fast in humans, obesity and elevated insulin promoted lean mass loss in males but not females.
https://doi.org/10.1172/jci.insight.
Robert A. Fenton & team show that a diet low in potassium causes bone loss in mice, effects that are attributable to altered calcium absorption by the kidney.
The figure shows deep learning instance segmentation model to identify kidney tubules and indicates low dietary K+ intake alters the abundance of the calcium-sensing receptor.
1Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
2Department of Biomedicine, Aarhus University, Aarhus, Denmark.
3Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
GDF15 signals energetic stress to the brain, leading to unpleasant symptoms as the body conserves and reallocates energy. In conditions such as frailty and cancer, suppression of GDF15 signaling is expected to lead to an improvement in symptoms, but potentially at the cost of long-term health and survival.
Jamaluddin et al. investigated how the MRAP2 accessory protein enhances signaling by three appetite-regulating GPCRs. MRAP2 disrupts GPCR oligomerization to form interactions, and its cytoplasmic region is essential for signaling. MRAP2 variants modulate receptor constitutive activity, enhance internalization, and reduce signaling, contributing to weight gain and hyperglycemia observed in humans.
A new study has for the first time elucidated the gut-liver immune regulatory axis jointly maintained by intestinal commensal bacteria and the intestinal endocrine system, and uncovered the fundamental mechanism underlying the bodyâs nonspecific clearance of drug delivery carriers. It provides a universal solution to the core problem plaguing the delivery field for decades, significantly improves the delivery efficiency and therapeutic effect of tumor-targeted therapy, mRNA therapy, gene editing and other treatments, and blazes a new trail for the clinical translation of biomedical delivery technologies.
The research team led by Professors Wang Yucai, Zhu Shu and Jiang Wei from the University of Science and Technology of China (USTC) published their research paper titled âCommensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectorsâ in Science on March 19.
The researchers present the first integrative catalogue of 267 cullinâRING substrate receptors, of which 93 are linked to germline disorders.
The most frequent substrate receptor (SR)-related diseases are neurodevelopmental, neuromuscular, and congenital organ/skeletal syndromes.
Disease associations are shaped by substrate context rather than tissue enriched expression.
Pathogenicity arises through altered degron recognition, disrupted complex assembly, dosage imbalance, or ubiquitinâproteasome system-independent functions.
Distinct variants in the same SR can yield divergent phenotypes, reflecting dosage sensitivity and developmental context.
Patient alleles inform diagnosis and therapeutic strategies, positioning SRs as central nodes connecting proteostasis, rare-disease genetics, and targeted protein degradation. sciencenewshighlights ScienceMission https://sciencemission.com/Cullin%E2%80%93RING-receptors
No matter the size or severity, wounds on human skin are difficult to monitor while they heal. Biopsies disrupt the wound site and are too invasive for routine, repeated monitoring, and most medical imaging devices that could do the job are large, expensive, and booked up with more pressing diagnostics. Clinicians typically resort to visual inspection or quick measurements of the woundâs size over time.
Based on research completed as part of a multi-year collaboration with Nokia Bell Labs, biomedical engineers at Duke University are developing a solution. Using a custom-built optical coherence tomography (OCT) imaging system together with artificial intelligence (AI) models grounded in a deep understanding of tissue regeneration, researchers have shown they can accurately and objectively measure the progress of wounds healing over time.
Using their new approach, the researchers also show that a hydrogel under development to improve wound healing works better with stiffer mechanical properties. The results are a two-for-one boon in a challenging area for both clinicians and researchers.
Working memory is a cognitive function that is essential for carrying out everyday activities and temporarily retaining information. This process enables us to understand information, learn and manage responses in a controlled mannerâabilities that are often impaired in certain neurodegenerative diseases. Now, a study published in Cell Reports has identified a molecular pathway in the brain that is crucial for the proper functioning of working memory.
The study, conducted using animal models, is led by Francisco José López-Murcia, a professor at the Faculty of Medicine and Health Sciences and the Institute of Neurosciences of the University of Barcelona (UBneuro), and a member of the Bellvitge Biomedical Research Institute (IDIBELL). The team led by Professor Nils Brose at the Max Planck Institute for Multidisciplinary Sciences (MPI-NAT, Göttingen, Germany) is also participating in the project.