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Transcription termination or pausing during DNA replication in bacteria and humans results in DNA damage with exposed 3′ single-stranded DNA ends and mutations.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

As the sample size goes down to the nanoscale, the surface-related mechanism plays an important role in the deformation of nanoscale crystals. Here, the authors report breakdown of the traditional Hall-Petch-like relation in nanoscale Ag attributed to diffusion-involved nucleation behaviors.

Tibetan adaptation to the high-altitude environment represents a case of natural selection during recent human evolution. Here the authors investigated the chromatin and transcriptional landscape of umbilical endothelial cells from Tibetan and Han Chinese donors and provide genome-wide characterization of the hypoxia regulatory network associated high-altitude adaptation.

Perovskite photovoltaics are the fastest-advancing solar technology but the mechanisms responsible for their performance are not clear. The observation of magnetic field effects in hybrid perovskites may help to explain their high efficiencies.

Cobalt(II) complexes of porphyrins have dominated the development of metalloradical catalysts. Now it has been shown that five-coordinate iron(III) complexes of porphyrins with an axial ligand are also potent metalloradical catalysts for olefin cyclopropanation. They are shown to react with different classes of diazo compounds via a stepwise radical mechanism.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Memory augmented neural network for lifelong on-device learning is bottlenecked by limited bandwidth in conventional hardware. Here, the authors demonstrate its efficient in-memristor realization with a close-software accuracy, supported by hashing and similarity search in crossbars.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Treg cells can be functionally altered by epigenetic modulators. Here the authors show that the histone H3K36 methyltransferase Setd2 is important for the survival of Treg cells and for the regulation of IL-33 mediated Th2 responses in mice and SETD2 expression is increased in Treg cells from human colorectal cancer tissue.

Despite their efficiency advantages, the performance of photonic neural networks is hampered by the accumulation of inherent systematic errors. Zheng et al. propose a dual backpropagation training approach, which allows the network to adapt to systematic errors, thus outperforming state-of-the-art in situ training approaches.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Unraveling the structural origin of liquid anomalies remains a challenging topic. Xu et al. propose a folded-network structural model for molten tin and provide insights into the observed second-order-like structural transition.

Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

Controlling and improving electron beam parameters are crucial for their application in free electron laser and X-ray sources. Here the authors generate quality electron beams with reduced energy spread from plasma accelerators by using a tailored escort electron bunch with the main accelerating bunch.

Understanding the short- and medium-range structure of metallic glasses remains a difficult challenge. The observation that the medium-range order has the characteristics of a fractal network may have broader implications in the understanding of the relation between structure and mechanical properties in metallic glasses.

Controlling various selectivities in radical reactions presents both formidable challenges and great opportunities. Now, Co(II)-based metalloradical catalysis has enabled the concurrent control of multiple convergences and selectivities in intermolecular radical allylic C−H amination. The reaction provides access to valuable chiral α-tertiary amines directly from an isomeric mixture of alkenes.

Zirconium phosphonate based metal-organic frameworks often exhibit superior chemical stabilities, but typically exist as poorly crystalline or amorphous materials. Here the authors exploit an ionothermal method to obtain highly porous and remarkably stable single crystalline zirconium phosphonate frameworks that can efficiently remove uranyl ions from aqueous solutions.

Pseudotyping messenger RNA-packaging virus-like particles with a glycoprotein recognizing a surface protein on dendritic cells led to higher humoral and adaptive immune responses in mice.

Understanding how cells discriminate between stimuli is an ongoing challenge. Here, the authors propose a mathematical framework for inferring the mutual information encoded in temporal signaling dynamics and use it to study how information is transmitted over time in response to different stimuli in NFκB, MAPK and p53 signaling pathways.

The competition between the formation of different phases and their kinetics need to be clearly understood to make materials with on-demand and multifaceted properties. Here, the authors reveal, by a combination of complementary in situ techniques, the mechanism of a Cu-Zr-Al metallic glass’s high propensity for metastable phase formation, which is partially through a kinetic mechanism of Al partitioning.

Deep-blue emitters and corresponding light-emitting devices are still in the progress to meet industrial standards. Here, the authors report catalytic interconversion of isomeric iridium(III) complexes and achieve true-blue emission and operational half-lifetime of over 10,000 h for tandem devices.

The repertoire of adaptive immune receptor is generated by V(D)J recombination, somatic rearrangements of V, D and J gene segments, in the respective loci. Here the authors show that the deficiency of Setd2, a histone methyl transfer, impairs V(D)J recombination and induces severe developmental blocks in both T and B lineages.

Detailed analysis of DNase-seq protocols reveals the importance of choosing the right enzyme concentration and fragment length and cautions that many transcription factor footprints may represent cutting bias.

The molecular and cellular underpinnings of cribriform prostate cancer aggressiveness remain to be explored. Here, the authors perform single-cell RNA-sequencing, TCR sequencing and histology and reveal cancer cell intrinsic pathways and an immunosuppressive tumour microenvironment.

While metallic glasses are expected to have tunable structures, these have rarely been demonstrated. Here, the authors combine temperature and pressure to show a two-way structural tuning in rare earth-based metallic glasses beyond the nearest-neighbor atomic shells.

The rational design of efficient water oxidation electrocatalysts is paramount to the development of electrochemical devices. Now, a Co-TiO₂ single-site catalyst is presented for alkaline water oxidation with high intrinsic activity, and its mechanism has been studied by grand canonical quantum mechanics calculations and in situ techniques.

Wood and colleagues report that the XPO1 inhibitor selinexor activates PI3Ky-dependent AKT signaling in AML via upregulation of P2RY2 and demonstrate a synergistic effect of combining selinexor with inhibition of prosurvival AKT signaling.

Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.

Analyses of data from high-throughput genomic technologies are challenging given large data dimensionality. Here, Liu and colleagues describe a method called MANCIE (Matrix Analysis and Normalization by Concordant Information Enhancement) that can conduct genomic data normalization and bias correction to detect biologically relevant information.

Whether a polymorphic transition exists in high entropy alloys or not remains unclear since discovery of these alloys more than a decade ago. Here authors report an irreversible polymorphic transition fromfcc to hcp in the prototype FeCoCrMnNi high entropy alloy and provide evidence for fccphase being more stable than hcp phase only at high temperatures.

Lithium-rich cathode materials in which manganese undergoes double redox could point the way for lithium-ion batteries to meet the capacity and energy density needs of portable electronics and electric vehicles.

The authors show that the deletion of ultraconserved TAD boundaries affects gene expression and phenotype, highlighting TAD evolution’s function. Human-specific TAD boundaries reveal a role in brain development and disease.

Lipophorin receptors (LpRs) regulate structural and functional development of neurons in Drosophila. Here authors demonstrate how short isoforms of LpR1 mediates astrocyte lipid shuttling to neuron through interacting with glia lipoprotein GLaz and the role of this pathway in dendritic morphogenesis in the fly brain.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Fungal infection induces signaling downstream C-type lectin receptors through the activation of the tyrosine kinase Syk. Xiao and colleagues show that the phosphatase SHP-2 recruits Syk to dectin-1.

Raised serum urate levels are a risk factor for gout, a common form of inflammatory arthritis. Here Li et al.conduct a multistage genome-wide association study in a Han Chinese population and identify three novel loci likely associated with the progression from hyperuricemia to gout.

FeCo nanoparticles with a graphitic carbon shell decorated with poly(ethylene glycol) have photothermal and magnetothermal properties and are sensitive tracers for magnetic particle imaging, magnetic resonance imaging and photoacoustic imaging.

Materials that show twinning-induced plasticity can offer unusual combinations of strength and ductility. Here, authors study deformation twinning and dislocation behaviour in a medium-entropy alloy CrCoNi and find a three-dimensional (3D) hierarchical twin network that forms from the activation of three twinning systems.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

A stable zinc-based metal–organic framework known to retain its porosity and crystallinity after exposure to moisture has been shown to undergo structural changes at the molecular level on adsorbing water. This dynamic and reversible response to the presence of water, including the rearrangement of bonds, is suggested to be the reason for the hydrolytic stability of this particular metal–organic framework.

Structural view of a dynamic molecular switch mechanism that governs repression and activation of the jasmonate plant hormone pathway.

The widely prescribed beta blocker carvedilol has strong antiarrhythmic effects on the heart, but the underlying mechanisms have been unclear. Qiang Zhou et al. now show that carvedilol, unlike other beta blockers, is also able to block proarrhythmogenic spontaneous calcium waves by directly inhibiting the calcium release channel RyR2. By generating new carvedilol analogs that inhibit RyR2 but not β-adrenergic receptors, the authors provide evidence that antiarrhythmic therapy might be optimized by combining agents that are individually selective for these two targets.

The dynamics of protein acetylation during infection remains unexplored. Here, Murray et al. characterize spatio-temporal acetylations of both cellular and viral proteins during HCMV infection, providing new functional insights into the host-virus acetylome that might help identify new antiviral targets.

Yeast-based screening identifies the benzodiazepine drug lorazepam as a non-selective positive allosteric modulator of the G-protein-coupled receptor (GPCR) GPR68; homology modelling and molecular docking of 3.1 million molecules found a new compound, ‘ogerin’, as a potent GPR68 modulator, which suppressed recall in fear conditioning in wild-type mice, and the general method of combining physical and structure-based screening may lead to the discovery of selective ligands for other GPCRs.