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Whole-genome duplication shaped cell-type evolution in the vertebrate brain
Abstract The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show...
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.
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.
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.
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.
Structural basis for chaperone-guided assembly of RNA-induced silencing complex
Abstract The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1,2,3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC).
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.
Human-Like Neural Nets by Catapulting
Human-like Neural Nets by Catapulting Speculative proposal to create artificial neural nets with human-like performance by high-learning-rate/regularization training of overparameterized NNs to trigger catapulting/grokking. Over-parameterization as a route to true generalization would resolve many outstanding mysteries of artificial versus natural intelligence. There are many mysteries about deep learning and human intelligence, but we could describe the biggest anomaly this way: why are...
The year in review: Influential people who have died in 2026
The year in review: Influential people who have died in 2026 He was a brash and outspoken media mogul who gave the world the 24-hour news cycle when he launched CNN - Bookmark He was a brash and outspoken media mogul who gave the world the 24-hour news cycle when he launched CNN. Ted Turner, who died in May, built a media empire that also included TNT, the Cartoon Network and Turner Classic Movies. In addition, he was a philanthropist, conservationist and owner of the Atlanta Braves baseball...