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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.
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).
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.
A 5.3-million-year-old deep-sea whale necropolis in the Diamantina Zone
Abstract Whale falls are biodiversity oases at seabeds1,2,3,4,5,6, yet their record from the oceans has remained sparse and fragmentary6,7. Here we report the discovery of a vast whale necropolis in the Diamantina Zone (4,616- to 7,001-m depth), extending about 1,200 km along the sea floor of the southeastern Indian Ocean. This area has a deep and extensive accumulation comprising five modern natural whale-fall communities and 476 fossil cetaceans recorded.
Empirical Approximation of $L_p$ Norms
arXiv:2606.00347v1 Announce Type: cross Abstract: We study empirical $L_p$ moments of a random vector $\pmb\varphi$ based on its i.i.d.\ copies $\pmb\varphi^1,\ldots,\pmb\varphi^m$, that is, $\frac1m\sum_{j=1}^m |\langle \pmb\varphi^j,y\rangle|^p$. Our main result is a new estimate for the expected uniform deviation \[ \mathbb{E}\sup_{y\in D}\biggl| \frac1m\sum_{j=1}^m |\langle \pmb\varphi^j,y\rangle|^p -\mathbb{E}|\langle \pmb\varphi,y\rangle|^p \biggr| \] over an arbitrary index set $D$....
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...
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.
Ultrafast machine learning on FPGAs via Kolmogorov-Arnold Networks
Ultrafast machine learning on FPGAs via Kolmogorov-Arnold Networks This post is a high-level explainer for my Master’s thesis, which involves designing hardware architectures for ultrafast inference and online learning using the Kolmogorov-Arnold Network (KAN) architecture. I’ll assume familiarity with standard machine learning concepts, as well as some understanding of hardware and digital circuits; read my previous post here for the latter. Please read the two papers below for more...
Diverse binding poses of agonistic neurotoxins on human Na<sub>v</sub>1.6
Abstract Voltage-gated sodium (Nav) channels are key targets of various venomous toxins. Deciphering the binding poses and mechanisms of action of representative toxins will help to dissect the functional mechanism of the channels and facilitate therapeutic development targeting Nav channels1,2. Here we present cryo-electron microscopy (cryo-EM) structures of distinct binding poses of three agonistic peptide toxins on the human Nav1.6–β1 channel complex.
Two-component exciton condensates in an electron–hole bilayer
Abstract Macroscopic quantum coherence emerges when bosons condense into a Bose–Einstein condensate (BEC)1,2,3,4,5. Excitons are a long-sought solid-state route to high-temperature BECs with strong interactions, electrical tunability and potentially multicomponent spinor order, but conclusive evidence for equilibrium condensation has remained elusive. Here we report evidence for two-component exciton BECs in MoSe2/hBN/WSe2 electron–hole bilayers6,7,8,9 by probing the spin–valley...