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The role of the cerebral cortex in cognitive and behavioral tasks is not fully understood.In this study, widefield imaging in freely moving mice navigating an 8-maze reveals global patterns of cortical activity. These cortical states represent multiple aspects of spatial decision making. Anterior and posterior state propagation is common and occurs throughout the maze, consistent with sensorimotor transformation and top-down control, respectively.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

Response to immune therapy varies among cancer types and individual cancer patients; thus, predictive biomarkers of success are urgently needed. Here, the authors present a computational framework that integrates tumor clonality and neoantigen characterization data to predict patient outcomes upon immune checkpoint inhibitor treatment.

Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Although the hedgehog (HH) pathway is known to be deregulated in medulloblastoma, inhibitors of the pathway have shown disappointing clinical benefit. Using single-cell sequencing in a mouse model of the disease, the authors show that the response to the HH pathway inhibitor vismodegib is cell-type specific.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Using a long-lived quantum-dot spin qubit coupled to a GaAs-based photonic crystal cavity, researchers demonstrate complete quantum control of an electron spin qubit. By cleverly controlling the charge state of the InAs quantum dot using laser pulses, optical initialization, control and readout of an electron spin are achieved.

Cavity-stimulated Raman spin-flip emission is demonstrated by coupling a negatively charged InAs/GaAs quantum dot to a photonic crystal defect cavity. The emission is spectrally narrow and tunable over a range of about 125 GHz. The process can be made spin selective by tuning the scattered photons to be in resonance with the cavity.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

Impacts from a climate event can cascade through natural, anthropogenic and socio-economic systems. Here the authors assess cascading climate impacts on the EU and identify intervention points for adaptation related to water, livelihoods, agriculture, infrastructure and economy, and violent conflict.

Roy et al. describe a generalized method for computationally designing miniproteins selective for a single integrin heterodimer and conformational state. The designed αvβ6 inhibitor remains monomeric and maintains biological activity following aerosolization and shows excellent efficacy in bleomycin induced lung fibrosis.

Intermediate-depth waters in the Atlantic and Pacific Oceans were well equilibrated with the atmosphere through the last deglaciation, according to radiocarbon data from deep-sea corals.

National implementation of a computed tomographic angiography and AI-diagnostic tool, CT-derived fractional flow reserve (FFR-CT), did not provide significant benefits in reducing mortality but led to fewer invasive coronary angiograms and downstream cardiac tests.

The 2.7 Å structure of the tetanus neurotoxin receptor binding fragment H_C reveals a jelly-roll domain and a β-trefoil domain. H_C retains the unique transport properties of the holotoxin and is capable of eliciting a protective immunological response against the full length holotoxin.

Whole-genome sequencing of 25 metastatic melanomas and matched germline DNA in humans reveals that the highest mutation load is associated with chronic sun exposure, and that the PREX2 gene is mutated in approximately 14 per cent of cases

Choby et al. show that dynamic increases in the copy number of preexisting β-lactamase genes in heteroresistance enables resistance of continua of cellular subpopulations, flexibly overcoming enhanced β-lactams without new evolution and threatening the β-lactam pipeline.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Spontaneous parthenogenesis in sunflower has been used to develop a scalable doubled haploid breeding system.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Hydrocephalus is a neurological disorder characterized by expansion of the ventricles. In a mouse model, the authors identified a role for neural progenitors and for platelet-derived growth factor signaling in the pathogenesis of neonatal hydrocephalus. Targeting this pathway reduced ventricular volume, pointing to a new therapeutic target for this condition.

A phase 2 randomized controlled trial of ustekinumab in 72 adolescents with recent-onset type 1 diabetes showed that treatment was well tolerated and β-cell function was 49% higher in the intervention group compared to the placebo arm after 12 months.

Here, the authors show that neutralization of human sera from both BNT162b2 vaccine recipients and from convalescent COVID-19 patients is less efficient against SARS- CoV-2 variants B.1.1.7 and B.1.351 and negatively associated with patient age.

The contribution of genetic factors to the tumour immune microenvironment (TIME) remains to be investigated. Here, the authors suggest the role of TIME eQTLs for target genes involved in reversing immune suppressive features.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

SPI1 fusion genes in T-cell acute lymphoblastic leukemia (T-ALL) are commonly found with co-occurring NRAS mutations. Here, the authors show that the combination of these oncogenes is necessary to drive T-ALL in a murine model and that the oncogenic activity of the SPI1 fusion is dependent on β-catenin.

A comparison of the evolutionary history and geographical spread of the antimicrobial-resistant pathogen Staphylococcus capitis in neonatal intensive care units indicates that acquisition of antibiotic resistance and increased competitiveness have led to the success of the NRCS-A S. capitis clone.