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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.

Nature 19h ago

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.

Nature 19h ago

Modi surpasses Nehru as longest-serving elected PM: Tracing the road to 4,399 days in 12 charts

'Modi hai to Mumkin hai', a popular catchphrase that has become synonymous with the BJP-led NDA government over the years. Indeed, this idea of "achieving the impossible" has often been projected as a hallmark of Prime Minister Narendra Modi's 12-year-long tenure at the helm. But even many of his supporters may not have imagined that one day their leader would make 'mumkin' what had remained impossible for other leaders for decades.

Times of India 13h ago

Teen sues McDonald’s franchise over harassment by accused murderer on their kitchen crew

Teen sues McDonald’s franchise over harassment by accused murderer on their kitchen crew Exclusive: For Chakota Nelson, 16, ‘the message from management wasn't 'I'm Lovin' It.' It was, 'We're Ignoring It,’ attorney David Keesling told The Independent - Bookmark An Oklahoma man accused nearly three decades ago of bludgeoning his former foster mother to death and setting her home ablaze found work at an area McDonald’s following his release from state custody, but “almost immediately” began...

The Independent World 6d ago

Taiwan’s Top Diplomat Opens Up About Trump’s Maneuvering

With President Donald Trump eyeing a $14 billion weapons sale to Taiwan as a “negotiating chip” with China, Alexander Tah-ray Yui is on the front lines of the effort to ensure the administration doesn’t buckle to Beijing. Yui serves as Taiwan’s top diplomat in the U.S., a role he’s held for the last two and a half years. But after spending much of that time behind the scenes to promote bipartisan support for the Asian democracy, he’s now been thrust into the role of...

Politico EU 4d ago

A prognostic human brain network for diffuse midline glioma

Abstract Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3,4,5,6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3,4,5,6,7,8,9 and other glial malignancies10,11,12 through paracrine mechanisms and direct neuron-to-glioma synapses.

Nature 19h ago

Blow to Trump as his LA mayor pick and former reality TV star Spencer Pratt knocked out of race

Blow to Trump as his LA mayor pick and former reality TV star Spencer Pratt knocked out of race Ex-reality TV star beaten into third place by leftist city council member Nithya Raman, according to latest projections - Bookmark - CommentsGo to comments Former reality TV star Spencer Pratt has been knocked out of the Los Angeles mayor’s race, according to the latest projections, a blow to Donald Trump after the president championed his candidacy. Democrat Karen Bass, the city’s incumbent...

The Independent World 1d ago

CNN star loses it on air over Trump gold phone and other branded merch: ‘Where does he find the time?’

CNN star loses it on air over Trump gold phone and other branded merch: ‘Where does he find the time?’ Anderson Cooper cracks up at the claim that the Trump Mobile is ‘made with American values in mind’ - Bookmark - CommentsGo to comments CNN anchor Anderson Cooper was unable to keep it together as he discussed President Donald Trump’s long-delayed gold smartphone and ever-expanding merchandise range. “Today, June 9, is not only primary day across a number of states where millions of...

The Independent World 5h ago

Iowa Is Back on the Map

You could be forgiven for ignoring the recent political goings-on in Iowa. The state, which was once a violet-hued hub of unpredictability, has lately elected and reelected Republicans. In last night’s primaries, though, Iowa Democrats nominated the kind of candidates the national party has struggled to find.

The Atlantic 6d ago