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 body’s 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 “Commensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectors” in Science on March 19.
The researchers present the first integrative catalogue of 267 cullin–RING 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 ubiquitin–proteasome 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 wound’s 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 manner—abilities 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.
Priti Agarwal, Ronen Zaidel-Bar et al. define the stage-specific gene expression programs of a leader cell that drives collective tissue invasion during organ development, identifying membrane trafficking as a central regulator of leader cell behavior.
Migration.
Collective cell invasion underlies organ development, epithelial repair, and cancer metastasis. “Leader cells” remodel ECM, sense guidance cues, reorganize their cytoskeleton, and coordinate follower cells, but the molecular programs enabling these functions remain unclear. Here, we present a stage-specific transcriptomic dataset of the Caenorhabditis elegans gonadal leader cell, the distal tip cell (DTC), which invades basement membrane and guides germ cells to form U-shaped gonadal arms. Comparing invasive larval-stage DTCs with noninvasive adult-stage DTCs defines the molecular signature of an actively invading leader cell in vivo. Our dataset recapitulates known regulators of gonad morphogenesis and reveals numerous uncharacterized genes with potential roles in leader cell activity. Demonstrating dataset utility, we identify vesicular trafficking proteins enriched in invading DTCs and demonstrate their importance for gonad development using endogenous tagging and DTC-specific RNAi. We also catalog diverse DTC-specific knockdown phenotypes. This resource establishes a molecular framework for leader cell activity and a platform to investigate conserved mechanisms of invasive migration.
Now online! A platform called MIST enables quantification and genotyping of infectious influenza in expelled respiratory particles, revealing diverse, individual-specific viral loads and aerosolized variants that correlate with saliva and nasopharyngeal viral loads and symptoms. Overall, the findings indicate heterogeneity in transmission potential.
A new form of in vivo CAR-T therapy kills leukemia, multiple myeloma, and sarcoma in mice, opening the door to a future off-the-shelf cancer treatment without chemotherapy.
For years, one of the most powerful weapons against certain blood cancers, called CAR-T therapy, has required an elaborate process: Doctors extract a patient’s immune cells, ship them to a specialized facility where they’re genetically reprogrammed to fight cancer, then ship them back for infusion into the patient’s bloodstream. This has revolutionized cancer treatment, but the time and expense place it out of reach for thousands of patients.
Now, scientists at UC San Francisco and UC Berkeley have developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating the barriers that have kept this life-saving therapy out of reach for many patients around the world.
https://doi.org/10.1172/jci.insight.
Here, Tobias B. Huber & team use a state-of-the-art, tour de force experimental design to show LSD1 regulates kidney development, and its dysfunction disrupts key kidney cells, leading to cyst formation in mouse and organoid models.
The image shows severe structural changes in the adult mouse kidney with loss of KDM1a. Nephrology.
4Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.
5Institute of Medical Bioinformatics and Systems Medicine and.
6Institute of Surgical Pathology, Faculty of Medicine, Medical Center — University of Freiburg, Freiburg, Germany.