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The ATR inhibitor ceralasertib has shown clinical activity in combination with immune-checkpoint inhibitors in several cancer types. Here the authors report the anti-tumor activity and the immunomodulatory changes, dependent on up-regulation of type I interferon pathway, following intermittent ATR inhibition in preclinical cancer models.

Sample processing for biological imaging experiments involves elaborate protocols with low reproducibility and throughput. Here the authors develop an open-source system called NanoJ-Fluidics, composed of off-the-shelf Lego components and an ImageJ-based controller to achieve automated fixation, labelling and imaging of cells.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

In the absence of recombination, the number of transposable elements (TEs) increases, but their accumulation dynamics are not well characterized. This study shows that TEs rapidly accumulated in non-recombining fungal mating-type chromosomes before reaching a plateau, possibly forming a TE reservoir.

Using scanning tunnelling microscopy and spectroscopy, fractional edge excitations are observed in nanographene spin chains, enabling the potential to study strongly correlated phases in purely organic materials.

BNT162b1 and BNT162b2 are two candidate mRNA vaccines against COVID-19 that elicit high virus-entry inhibition titres in mice, elicit high virus-neutralizing titres in rhesus macaques and protect macaques from SARS-CoV-2 challenge.

Transcriptional changes during prostate cancer progression are not yet fully understood. Here, the authors integrate a transcriptomics atlas of prostate cancer and validate it with preclinical models and single-cell RNA-seq, revealing the role of EZH2 and macrophage polarisation in tumour progression.

Lerma-Martin et al. generated a paired single-nucleus RNA sequencing and spatial transcriptomics dataset from subcortical multiple sclerosis lesions, identifying spatial niches and key cell interactions driving inflammation and disease progression at the lesion rim.

“Out of one, many”. The authors show that, despite binding to a common network of genes, two transcription factors each have their own set of direct targets (also known as their ‘regulon’). Thus, out of one bound network, many regulons are possible.

This study shows that tonically active, delta subunit–containing presynaptic GABA_A receptors facilitate excitatory synaptic transmission at hippocampal mossy fiber synapses. Presynaptic GABA_A receptors depolarize presynaptic boutons, enhance calcium entry evoked by action potentials and facilitate LTP induction in mossy fiber–CA3 synapses.

The combination of deep chromatin immunoprecipitation–sequencing with a statistical test that scores the correlation of peak height and allelic imbalance allows de novo discovery of histone acetylation quantitative trait loci without prior genotyping or genome sequencing.

Nanographenes, as their name suggests, are small sections of graphene. They offer a diverse array of magnetic behaviors; for example, sublattice imbalances in the nanographene lead to unpaired spins. Here, Du et al uncover a large variation in the exchange energy in nanographenes, due to changes in the frontier orbital symmetries.

Modelling a planktonic ecosystem in the ocean is challenging as it is embedded in a patch of water that is continuously moving, stretching, and diluting. This study introduces a new theoretical framework to account for such aspects, tracking a patch of water hosting a drifting ecosystem, along with its physical, environmental and biochemical features.

The availability of pervasive data has opened up possibilities for quantitative approaches to many phenomena, but extracting useful information from huge datasets is difficult. Here, Louail et al. propose a method to extract a coarse-grained signature of large weighted networks and apply it to mobility networks.

Cryoelectron microscopy, cryoelectron tomography and proteomics are used to resolve the 96-nm modular repeat of axonemal doublet microtubules from both sperm flagella and epithelial cilia of the oviduct, brain ventricles and respiratory tract.

Comprehensive profiling of a circumventricular organ with leaky blood vessels, and comparison to cortex vasculature reveal that blood–brain barrier heterogeneity reflects differences in endothelial cells and their interactions with perivascular cells.

Contact-dependent growth inhibition (CDI) is an important mechanism of bacterial competition. Here, Bartelli et al. show that proteolytic processing of a CDI toxin induces a conformational switch required for translocation into target bacteria.

Bathymetric surveys of the submarine Congo Canyon show damming by canyon-flank landslides led to the temporary storage of substantial masses of sediment and organic carbon, interrupting their transport to the deep sea.

Genomic, transcriptomic and epigenetic analyses of malignant pleural mesothelioma identify molecular axes and specialized tumor profiles underlying intertumoral heterogeneity.

Giant cell lesions of the jaw (GCLJ) are debilitating benign tumors of unclear origin. The authors identify driver recurrent somatic mutations in TRPV4, KRAS and FGFR1 and show they converge on aberrant activation of the MAPK pathway. Their findings extend the spectrum of TRPV4 channelopathies and provide rationale for targeted therapies at the bedside in GCLJ.

Genome-wide histone acetylation profiling in cohorts of patients with active and latent tuberculosis reveals acetylation changes in host immune cells modulating potassium channel expression and apoptosis response.

Following instruction by a morphogen secreting centre, aggregates of mouse embryonic stem cells develop into embryo-like structures organized around an axial mesoderm, which show extensive characteristics of a neurula-stage mouse embryo, with antero-posterior and dorso-ventral patterning of germ layer derivatives.

The E3 ubiquitin ligase TRIM7 polyubiquitinates the envelope protein of Zika virus, adding Lys63-linked polyubiquitin chains that interact with the TIM1 receptor of host cells to enhance virus entry and replication.

Analysis of genomic networks from 430 modern individuals across 21 Pacific island populations reveals the human settlement history of Polynesia.

The reasons why malaria manifests with a variety of well-recognized clinical phenotypes remain poorly understood. Here, using distinct rodent models, the authors reveal that the microbiota colonizing the lung promotes respiratory distress syndrome and mortality during malaria infections.

Screening of hundreds of nanoparticle polymers identifies an effective and low-toxicity formulation for the functional delivery of RNA to the lungs of distinct animal species.

Deletions of chromosome 22q13.3 cause Phelan–McDermid syndrome (PMDS), a neurodevelopmental disorder associated with autism; here induced pluripotent stem cells from PMDS patients with autism are used to produce neurons, they are shown to have reduced SHANK3 expression and a defect in excitatory synaptic transmission which can be restored either by increasing SHANK3 or with insulin-like growth factor 1.

Bischof and colleagues report that AP-1 bookmarks prospective senescence enhancers for future activation to achieve a timely execution of the senescence programme.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Brinton, Uauy and colleagues utilize genomic data from the 10+ Wheat Genome Project to develop a useful tool for studying and generating new wheat cultivars. This framework uses advanced exploitation of wheat haplotypes to bring newfound precision and efficiency to wheat breeding.

Mouse models of muscle injuries and ageing characterized by low levels of intra-tissue glutamine are ameliorated by macrophage-specific deletion or systemic pharmacological inhibition of glutamate dehydrogenase 1, which results in constitutively high activity of glutamine synthetase.

Analysis of ancient proteins suggests that Early Bronze Age dairying and horse domestication catalysed eastern Yamnaya migrations.

Here the authors show that a Newcastle disease virus based COVID-19 vaccine expressing a stabilized spike protein induces protective immunity in small animal models and reduces replication of variants of concerns. This vaccine candidate can be produced by influenza virus vaccine manufactures around the world.

A ‘triangulation’ approach combining linguistics, archaeology and genetics suggests that the origin and spread of Transeurasian family of languages can be traced back to early millet farmers in Neolithic North East Asia.

Analysis of individual-level patient records from Brazil reveals that the extensive shocks in COVID-19 mortality rates are associated with pre-pandemic geographic inequities as well as shortages in healthcare capacity during the pandemic.

In patients with high-grade serous ovarian cancer, robust and protective humoral responses are dominated by B-cell-derived polyclonal IgA that binds to polymeric IgA receptors that are universally expressed on ovarian cancer cells.

Wherry and colleagues define the kinetics of vaccine-primed recall immune responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection, highlighting rapid activation of memory T cells and broadly enhanced immune responses in previously vaccinated individuals.

Here the authors demonstrate that the SARS-CoV-2 main protease (Mpro) is subject to redox regulation in vitro, reversibly switching between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues.

The authors test expansion microscopy protocols for investigation of the molecular organisation of mammalian synaptonemal complexes (SCs) with structured illumination microscopy. They show that the molecular structure is preserved during expansion and ultrastructural details of SCs can be revealed.

Pasare and colleagues describe an inflammasome-independent, TNFR–Fas–caspase-8-dependent pathway of IL-1β production triggered by cognate interactions between effector CD4⁺ T cells and mononuclear phagocytes.

Currently available Raman scanners are limited in speed to acquire images of clinically relevant sizes in cancer imaging. Here, the authors developed a DNA based design principle for Raman-Fluorescence bimodal nanoparticles and demonstrate real-time, high precision image-guided tumor resections and photothermal ablation of cancer.

2D crystals of the MloK1 potassium channel diffract to only 10 Å. Here the authors present a method, where they apply cryo-EM single-particle image processing to recorded 2D crystal images, which reveals conformational conformational variability of MloK1 within the crystals and enabled them to determine the structure at 4 Å resolution.

Comparison of multiple genome assemblies from wheat reveals extensive diversity that results from the complex breeding history of wheat and provides a basis for further potential improvements to this important food crop.

Stress relaxation in cell monolayers shows remarkable similarities with that of single cells, suggesting the rheology of epithelial tissues is mediated by the actomyosin cortex—with dynamics reminiscent of those on a cellular level.