Preferential insertion into the late-replicating inactive X explains L1 accumulation in this chromosome.

Changes in lysosomal metabolites are associated with both aging organs and lysosomal storage diseases.

The Great American Biotic Interchange informs the dynamics of modern species invasions.

Calcareous marine plankton can indicate past and present ocean acidification.

Heme biosynthesis is tightly coordinated to support essential functions without accumulating toxic porphyrins and depleting cellular iron. Heme induces degradation of the heme biosynthetic enzyme, 5-aminolevulinate synthase (ALAS), by the mitochondrial caseinolytic protease complex CLPX-CLPP (CLPXP), but the mechanism for heme-triggered degradation had not been elucidated. We found that polymerase delta-interacting protein 2 (POLDIP2) is a heme-sensing adaptor protein sufficient to reconstitute negative feedback degradation of ALAS by CLPXP. POLDIP2 was necessary to support ALAS turnover in cells and regulate heme production during erythropoiesis. POLDIP2 directly recognized and recruited heme-bound ALAS to CLPXP. Degradation initiation required a carboxyl-terminal element of ALAS, truncations of which cause an erythropoietic protoporphyria. Our findings establish a mechanism for conditional degradation by CLPXP that underlies erythropoietic protoporphyrias linked to CLPX and ALAS.

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Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age, preceding organismal decline. Caloric restriction, a lifespan-extending intervention, mitigated these changes in the heart and muscle but not the brain. Our findings link lysosomal storage disorders to aging-related dysfunction and open avenues for the mechanistic investigation of how lysosomal functions deteriorate during aging and in age-associated diseases.

The Kondo effect is a prototypical quantum phenomenon arising from the interaction between localized electrons in a magnetic impurity and itinerant electrons in a metallic host. Although this phenomenon has served as the testing ground for quantum many-body methods for decades, the precise description of Kondo physics with material specificity remains challenging. Here, we present a systematic ab initio approach to converge toward an exact zero-temperature electronic treatment of Kondo correlations. Across a series of 3d transition metals, we extracted Kondo temperatures matching subtle experimental trends, with accuracy exceeding that of standard models. We further obtained microscopic insight into the origin of these trends. More broadly, we demonstrate the possibility to start from fully ab initio many-body simulations and push toward the realm of converged predictions.

Appel halogenation reactions are widely used to convert alcohols to alkyl halides but are not suitable to prepare alkyl fluorides because fluoride is sequestered as a difluorophosphorane. In this work, we introduce bench-stable neopentoxyphosphonium salts to solve this enduring challenge. With these reagents, various alcohols undergo fluorination with potassium fluoride under hydrogen bonding phase-transfer catalysis, a manifold offering a pathway to enantioselective fluorination of alcohols. Mechanistically, a neopentoxyfluorophosphorane is formed, which undergoes reversible exchange with the alcohol substrate in preference to difluorophosphorane formation. The catalyst assists with potassium fluoride solubilization and with phosphorus-fluorine bond dissociation, leading to the alkoxyphosphonium fluoride ion pair undergoing stereoinvertive fluorination. Turnover results from stronger binding of the catalyst to fluoride than phosphine oxide, the by-product of the reaction, which is recyclable as starting material for the synthesis of the phosphonium reagents.

Policy Evidence Readiness Levels help decision-makers assess evidence maturity and uncertainty.

" Landmark" paper finds European contact introduced the disease.

Collagen, a fundamental constituent of the extracellular matrix, has long remained elusive to high-resolution structural characterization. Using a tailored system and optimized cryo-electron microscopy processing for long-period filaments, we determined the structure of native collagen fibrils from the porcine vitreous body, with local resolutions extending from 2.6 to 7 angstroms. Each 67-nanometer periodic unit contains type II, V/XI, and IX collagen triple helices together with opticin, at a stoichiometry of 8:4:4:4, which reveals their detailed higher-order molecular packing. Abundant galactose-glucose disaccharides modify hydroxylysine residues in conserved -glycine-X-hydroxylysine- motifs, mediating fibril packing and structural stability. Our structure uncovers the glycan-mediated assembly principle of collagen fibrils and clarifies the structure-function basis of collagens in the vitreous body.

More than half of AI "unicorns" have never published a paper or preprint.

Fullerene-based electron transport layers (ETLs) used in inverted (p-i-n) perovskite solar cells face issues regarding cost, scalability, and instability, whereas highly stable inorganic oxides feature unfavorable energy alignment and enhance hysteresis, which reduce power conversion efficiency (PCE). We report a nonfullerene conjugated polymer, 2PB-T, that incorporates coplanar and electron-withdrawing perylene bisimide (PBI) units into its backbone. The PBI polymeric backbone and side-chain engineering address the instability of small-molecule ETLs by optimizing electron transport properties, film uniformity, and interfacial binding. Small-area devices achieved a champion PCE of 27.8%, with a certified maximum power point tracking (MPPT) efficiency of 27.3%. Perovskite modules with areas of 20.6 and 625 square centimeters reached PCEs of 24.4 and 22.5%, respectively. Small-area devices retained more than 98.6% of their initial PCE after 1752 hours of continuous MPPT at 85°C in air, and the 625-square-centimeter module maintained 96.9% of its initial PCE after 5900 hours of outdoor operation.