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Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer
Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.
A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases
Abstract Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor...
Data gaps of international databases on HPAI H5 in wildlife in the Americas: implications for surveillance, research, and conservation
Global efforts to prevent and mitigate the impacts of high pathogenicity avian influenza (HPAI) H5 on domestic animals, humans, and wildlife rely on timely and transparent information that is both accurate and interpretable across countries and sectors. International epidemiological and genomic databases, such as the World Animal Health Information System (WAHIS), the Global Animal Disease Information System (EMPRES-i+), the Global Initiative on Sharing All Influenza Data (GISAID), and the...
Scientists discover inherited traits that break Mendel’s Laws of genetics
Scientists discover inherited traits that break Mendel’s Laws of genetics - Date: - June 1, 2026 - Source: - Johns Hopkins Medicine - Summary: - A major mouse study found that some inherited traits are passed down through epigenetic changes that break the classic rules of genetics. Researchers discovered hundreds of cases where these chemical DNA marks behaved unexpectedly, including some that seemed to emerge out of nowhere. They also identified the first known naturally occurring...
Mutation-dependent responses to sleep and exercise in clonal haematopoiesis
Abstract Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle.
SIRT7 regulates dosage compensation and safeguards the female X chromosome
Abstract Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3,4,5,6,7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan.
Mitochondria directly interact with the nuclear pore complex
Abstract Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5.
How do you stop Ebola at the World Cup?
LOS ANGELES — When the United States, Canada and Mexico formally submitted their co-hosting bid to soccer governing body FIFA in 2018, they touted the safety of the region, noting “no major endemic infectious diseases across any of our Host Countries.” Now, as the three countries prepare to welcome one of the largest international gatherings around the globe since the Covid-19 pandemic, infectious diseases are front of mind. Of particular concern is an outbreak of...
How do you stop Ebola at the World Cup?
LOS ANGELES — When the United States, Canada and Mexico formally submitted their co-hosting bid to soccer governing body FIFA in 2018, they touted the safety of the region, noting “no major endemic infectious diseases across any of our Host Countries.” Now, as the three countries prepare to welcome one of the largest international gatherings around the globe since the Covid-19 pandemic, infectious diseases are front of mind. Of particular concern is an outbreak of Ebola that is...
Research project provides new estimates of greater amberjack abundance in U.S. South Atlantic, Gulf of America
Research project provides new estimates of greater amberjack abundance in U.S. South Atlantic, Gulf of America Sadie Harley Scientific Editor Andrew Zinin Lead Editor A multi-year research project has provided new insight into greater amberjack. The Greater Amberjack Count was led by Sean P. Powers, Ph.D., fisheries ecology professor and Director of the Stokes School of Marine and Environmental Sciences of the University of South Alabama. A team of 20 scientists from more than a dozen...