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Genomic integration of an adeno-associated virus vector in a mouse model of Angelman syndrome unsilences paternal Ube3a and rescues anatomical and behavioural phenotypes, suggesting a pathway towards the treatment of this neurodevelopmental disorder.
Scalable optics co-fabricated with a cryogenic surface-electrode ion trap are used to drive high-fidelity multi-ion quantum logic gates, demonstrating a route to simultaneously scale and reduce errors in quantum processors.
Mother cells recycle parental MCMs and simultaneously synthesize nascent MCMs, both of which are inherited by daughter cells, in which the former are preferentially used to form active replisomes and the latter adjust the pace of replisome movement to minimize errors during DNA replication.
Depletion of transforming growth factor-β receptor 2 (TGFBR2) in CD4+ T cells results in IL-4-dependent vascular remodelling, stopping tumour growth in a transgenic mouse model of breast cancer, suggesting that type 2 immunity could be targeted for cancer treatments.
A high-throughput assay that introduces mismatched base pairs into the DNA sequence shows that mismatches can increase transcription factor binding affinity by prepaying some of the energetic cost of distorting the DNA.
4T-Trap, a bispecific molecule designed to recognize CD4 and bind TGF-β, blocks TGF-β signalling in T helper cells, causing interleukin-4-dependent vascular reorganization and cancer cell death in a mouse model of breast cancer.
The architecture of planetary systems is shown to be strongly affected by stellar clustering in position-velocity phase space; hot Jupiters occur preferentially at high density, suggesting that their extreme orbits originate from environmental perturbations.
Inverted-repeat Alu elements are the main source of drug-induced immunogenic double-stranded RNAs, which are destabilized by the RNA deaminase ADAR1, thereby limiting activation of the immune response.
A jigsaw-style configuration of interlocking structures identified in the elytra of the remarkably tough diabolical ironclad beetle, Phloeodes diabolicus, is used to inspire crush-resistant multilayer composites for engineering joints.
Analysis of global three-dimensional shear attenuation and velocity models implies that partial melting in the seismic low-velocity zone enables motion of oceanic plates by reducing the viscosity of the asthenosphere.
A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution.
Multicriteria optimization identifies global priority areas for ecosystem restoration and estimates their benefits for biodiversity and climate, providing cost–benefit analyses that highlight the importance of optimizing spatial planning and incorporating several biomes in restoration strategies.
High oxidation resistance, without degradation of thermal or electrical conductivity, is achieved in copper using surface modification by a solvothermal or electrochemical treatment with sodium formate and formation of a thin surface coordination layer.
Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.
The authors uncover the diverse transcriptomic cell types of thirst-driving neurons in the lamina terminalis and show that unique combinations of neuron types respond to and mediate distinct thirst states.
Deep learning was used to map the crown sizes of each tree in the West African Sahara, Sahel and sub-humid zone using submetre-resolution satellite imagery, revealing a relatively high density of trees in arid areas.
Telomeric-repeat-containing RNA is recruited to telomeres by a mechanism that involves the DNA recombinase RAD51 and the formation of DNA–RNA hybrids, or R-loops—a process similar to that involved in homology-directed DNA repair.
The concept of neuromorphic completeness and a system hierarchy for neuromorphic computing are presented, which could improve programming-language portability, hardware completeness and compilation feasibility of brain-inspired computing systems
Single-cell analysis of blood vessels in the alveolus, the site of chronic disease and virus-induced lung injury, reveals two intermingled endothelial cell types with specialized gas exchange and stem cell functions.
A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.
Modelling reveals how thick diamondiferous continental mantle ‘keels’ were formed only at increased mantle temperatures when the melt-depleted, hot, ductile mantle located under subducting oceanic plates flowed backwards, underplating the continents.
Analysis of cis-regulatory chromatin interactions, open chromatin and transcriptomes for different cell types isolated from mid-gestational human cortex samples provides insights into gene regulation during development.
By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.
Cryo-electron microscopy structures of the bacterial recombination protein RecA with DNA, and of RecA–D-loop complexes, provide insights into the double-stranded DNA opening, homology search and strand-exchange processes of homologous recombination.
The long-term success of area-based conservation—including both protected areas and other effective area-based conservation measures—after 2020 will depend on governments securing adequate funding and prioritizing biodiversity in land, water and sea management.
The current state of programmable photonic integrated circuits is discussed, including recent developments in their building blocks, circuit architectures, electronic control and programming strategies, as well as different application spaces.
Stable isotope data for Southeast Asian mammals across the Quaternary period shed light on environmental change from the Early Pleistocene to the Holocene epoch, contextualizing hominin evolution and megafauna extinction in the region.