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An automated perfusable microfluidic bioreactor can generate clinical doses of viable CAR T cells that are functionally comparable to cells produced in standard open-culture systems.

The authors present a fluorescent probe that tracks glutamine in live cells. They demonstrate the capabilities of the probe by providing direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions.

In 2022, the zoonotic Langya virus caused cases of severe pneumonia in humans. Here, the authors determine the structure of the fusion glycoprotein of Langya virus and demonstrate antigenic but not structural divergence from bat-borne henipaviruses, yielding insights for future vaccine designs.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

In the LUMINA-1 trial for fibrodysplasia ossificans progressiva, garetosmab, an activin A monoclonal antibody, did not lead to significant changes in heterotopic ossification lesion activity in pre-existing lesions in period 1. Garetosmab prevented the formation of new lesions in both periods 1 and 2.

ALS-linked mutations in FUS trigger defects within the nucleocytoplasmic transport pathway in human neurons and Drosophila. Aberrant interactions between FUS and nucleoporins are thought to underlie these defects.

Behaviorally relevant neural rhythms have been mainly studied at the neural population level. Here, the authors show that subthreshold membrane voltage delta-frequency oscillations in individual striatal cholinergic neurons modulate spike timing, striatal network beta rhythmicity, and track patterned stepping movement.

B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive.

IgE antibodies targeting cancer antigens can be used for immunotherapy. Here the authors present an IgE antibody targeting the melanoma-associated antigen, chondroitin sulphate proteoglycan 4, that recognises human melanoma, stimulates tumour cell cytotoxicity, and restricts tumour growth in humanised mouse models.

Aperiodic structure imaging suffers limitations when utilizing Fourier analysis. The authors report an algorithm that quantitatively overcomes these limitations based on nonconvex optimization, demonstrated by studying aperiodic structures via the phase sensitive interference in STM images.

Walsh and colleagues use prospective sequencing in a large cohort of pediatric patients with solid tumors to detect mutations in cancer predisposition genes and guide downstream clinical care.

Rapid ocean deoxygenation during the Early Cretaceous OAE1a is shown to provide evidence for a strong link between volcanic CO₂ emissions, weathering and ocean oxygen content that is characterized by a climate threshold.

Increased risk of premature cardiovascular disease in systemic lupus erythematosus (SLE) is not well understood, but in animal models, the Janus kinase inhibitor tofacitinib improves related phenotypes. Here the authors report a Phase 1 double-blind randomized trial that shows tofacitinib is safe and well tolerated in in patients with SLE.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Tumor cell in the peritoneum are often exposed to shear forces generated by ascitic flow during metastasis. Here, the authors show that metastatic cancer stem cells tether more and roll slower than the non-metastatic counterparts, and that sialyl-Lewis^x -P-selectin axis mediates peritoneal metastasis.

HiFi genome sequencing accesses DNA methylation and nucleotide variation in long sequence reads. Here, the authors apply this approach in a rare disease cohort to identify DNA hypermethylation linked to genetic variants including rare disease alleles.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Jeffrey Weiser and his colleagues provide a mechanism for a beneficial effect from commensal bacteria that colonize the gut. They show that peptidoglycan from gut microbiota traverses the gut mucosa and boosts the systemic innate immune response by priming neutrophils in the bone marrow. Such priming requires the recognition of peptidoglycan by the intracellular receptor Nod-1 (pages 160–161).

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

Some patients present with multiple lung tumours but it is unclear whether these are metastases or individual lesions. Here, the authors use genomics techniques to demonstrate in six patients that multiple tumours have individual genetic profiles and represent separate tumours.

Carbon isotopic analysis reveals global biogeographic traits in shark trophic interactions, and sheds light on the diverse foraging behaviour of sharks.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Short stature is a hallmark of Werner Syndrome, but the underlying mechanisms are not well studied. Here they report that WRN regulates bone development and growth by opening SHOX-G-quadruplexes via its helicase activity both in vitro and in vivo.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Infection with SARS-CoV2 and the development of Coronavirus disease 2019 (COVID-19) has been linked to induction of autoimmunity and autoantibody production. Here the authors characterise the new-onset IgG autoantibody response in hospitalised patients with COVID-19 which they correlate to the magnitude of the SARS-CoV2 response.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Surface proteins are shown to be routed to the outer Gram-positive cell-wall surface by entropy.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Single-cell RNA sequencing and T cell receptor sequencing are combined to identify transcriptional programs specific to mutation-associated neoantigen-specific T cells in non-small cell lung cancers treated with anti-PD-1, providing insights into resistance to PD-1 blockade.

The incidence of type 1 diabetes is increasing, potentially implicating non-genetic factors. Here the authors conduct an epigenome-wide association study in disease-discordant twins and find increased DNA methylation variability at genes associated with immune cell metabolism and the cell cycle.