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Two sequence-verified, clonal, publicly available collections of human open reading frames are reported. One collection is in a lentiviral vector for expression in mammalian cells; the other is in the Gateway vector system.

Researchers describe a mechanism capable of compressing fast and intense X-ray pulses through the rapid loss of crystalline periodicity. It is hoped that this concept, combined with X-ray free-electron laser technology, will allow scientists to obtain structural information at atomic resolutions.

Here, using cryogenic electron microscopy and cryoDRGN, the authors delineate how the anaphase-promoting complex/cyclosome is reconfigurated to interact with its cognate E2s and thus polyubiquitinate its target. Unexpectedly, multiple ubiquitin moieties are shown to interact with the anaphase-promoting complex/cyclosome machinery, including its activator Cdh1.

Air-based acousto-optic modulation is shown to be able to efficiently control gigawatt-scale, ultrashort laser pulses.

Integrating independent large-scale pharmacogenomic screens can enable unprecedented characterization of genetic vulnerabilities in cancers. Here, the authors show that the two largest independent CRISPR-Cas9 gene-dependency screens are concordant, paving the way for joint analysis of the data sets.

Analysis of genomic and clinical features of acute erythroid leukemia in comparison to other myeloid disorders supports its distinct classification, defines subgroups and suggests therapeutic vulnerabilities.

Mutations of the SWI/SNF chromatin-remodeling complex member SMARCB1 can cause malignant rhaboid tumors. Here the authors report a BRD9-containing SWI/SNF subcomplex that lacks SMARCB1 and its requirement for the survival of rhaboid tumors.

A highly selective inhibitor of the DCLK1/2 kinases is used to uncover the consequences of DCLK1 inhibition on viability, phosphosignaling and the transcriptome in patient-derived organoid models of pancreatic ductal adenocarcinoma.

The X-ray crystal structure of the potassium channel TASK-1 reveals the presence of an X-gate, which traps small-molecule inhibitors in the intramembrane vestibule and explains their low washout rates from the channel.

SMNDC1 is a splicing factor that binds arginine methylation with its Tudor domain. Here, the authors study the protein’s phase-separating behavior and develop small-molecule Tudor domain inhibitors that perturb SMNDC1 function.

Persistent activity can mediate working memory during behavior. Here, the authors report persistent activity during sleep, occurring spontaneously in medial entorhinal cortex layer III (MECIII) neurons' membrane potential. This persistent activity excited hippocampal CA1 neurons. Thus, persistent activity in MECIII contributes to cortico-hippocampal interaction, which could serve several important mnemonic functions.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

A copper oxide high-temperature superconductor magnet generates a direct-current magnetic field of 45.5 tesla—the highest value reported so far—using a design that enables operation at high current densities.

Understanding the drivers of forest losses and their economic implications is key to designing efficient climate policies. This study simulates market-driven land-use decisions to identify the factors contributing to forest losses, revealing such losses, their trends, temporal variation and social value.

Albena Jordanova and colleagues report mutations in HINT1 in autosomal recessive axonal neuropathy with neuromyotonia. Using linkage analysis and whole-genome sequencing, they identify 8 mutations in 33 affected families.

Recent improvements in the indirect-drive inertial confinement fusion experiments include the achievement of burning plasma state. Here the authors report the scaling of neutron yield in a burning plasma of Deuterium-Tritium fusion reaction by including the mode-2 asymmetry.

A pediatric cancer dependency map generated with genome-scale CRISPR–Cas9 loss-of-function screens in 82 pediatric cancer cell lines highlights genetic dependencies across a range of tumor types.

It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation.

Golub and colleagues identify the phosphate exporter XPR1 as a therapeutic vulnerability in ovarian and uterine cancers, and show that phosphate efflux inhibition reduces tumor cell viability through accumulation of intracellular phosphate.

Changes in intracellular GTP levels are not considered as a regulatory event in RAC1 activation in live cells since total GTP levels are substantially higher than the RAC1 GTP dissociation constant determined in vitro. Here, the authors demonstrate that the availability of free GTP in live cells controls the activity of RAC1 and cell invasion.

Girdhar et al. constructed chromosomal domains from prefrontal histone acetylation and methylation maps and discovered, in a large cohort of schizophrenia and bipolar brains, converging alignment by genetic risk, neuronal function and three-dimensional genomics.

Electrocatalyst development is key to improving the performance and viability of many electrochemical energy technologies. Here, the authors design Ag-Pd alloys with specifically tuned electronic structures to have enhanced oxygen reduction electrocatalysis and decreased precious metal content.

Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.

Breen et al. map RNA editing profiles in cortical samples from individuals with schizophrenia and controls, and find links between altered RNA editing in glutamatergic and postsynaptic density genes and schizophrenia genetic risk architecture.

A future carbon-free energy economy requires an efficient photocatalytic route to hydrogen generation. Here, the authors employ surface modification techniques to raise the performance of an unassisted solar water splitting device to achieve exceptional performances.

This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.

Electrochemical CO₂ reduction is a potential route to the sustainable production of valuable fuels and chemicals. In this joint experimental-theoretical work, the authors address the issue of the rate-limiting step on Gold and present insights from multi-scale simulations into the importance of the electric double layer on reaction kinetics and mass transport.

Microglia in the aging hippocampus accumulate lipid droplets, and are functionally impaired and inflamed. Lipid droplet formation in microglia is regulated by genes linked to neurodegeneration such as progranulin.

iNOS-driven dysregulation of the IRE1α–XBP1 pathway leads to cardiomyocyte dysfunction in mice and recapitulates the systemic and cardiovascular features of human heart failure with preserved ejection fraction.

Whole-genome sequencing and comparative genomic analysis of immune-related genes of Cercocebus atys and Macaca mulatta identify candidate genes, such as ICAM2 and TLR4, that may explain the AIDS resistance of C. atys.

The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

Sirtuins are involved in the regulation of responses to diverse types of cellular stress. Here the authors describe the SirT6-dependent cysteine monoubiquitination of the histone methyltransferase Suv39h1 as part of a regulatory circuit for the NF-κB pathway.

Achieving higher efficiencies for thin-film solar cells always requires identification of the limiting factors. Here Krause et al. show that inhomogeneously distributed net doping or lifetime have little impact while recombination at grain boundaries is one of the main loss mechanisms for high performance Cu(In,Ga)Se₂ solar cells.