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Potent allogeneic CD8αβ⁺ CAR T cells devoid of alloreactive potential can be generated from human T-cell-derived induced pluripotent stem cells via the timed and calibrated expression of a CAR that substitutes for the T-cell receptor.

Targeted spatial transcriptomics mapped olfactory receptor mRNAs to sections of the murine olfactory bulb to generate an interactive, statistical, 3D model of glomeruli locations and identify an ultra-sensitive receptor-odorant relationship.

Boyer et al. created genetic mouse models of muscular dystrophy in which satellite cells were selectively depleted. The depletion of satellite cells at select times was protective. Myofibers no longer had plasma membrane instability leading to tissue wasting in the muscular dystrophies.

Retinal pigment epithelial cells are identified as a local source of insulin in the retina, which is stimulated by phagocytosis of photoreceptor outer segments and starvation and has the potential to influence retinal physiology and disease.

Synthetic health data have the potential to mitigate privacy concerns when sharing data to support biomedical research and the development of innovative healthcare applications. In this work, the authors introduce a use case oriented benchmarking framework to evaluate data synthesis models through a set of utility and privacy metrics.

An approach to design proteins that can capture amyloidogenic protein regions present in, for example, tau and Aβ42 has now been developed. These designer proteins can inhibit the formation of pathogenic amyloid fibrils and protect cells from toxic species.

The cellular levels of the critical coenzyme nicotinamide adenine dinucleotide (NAD)⁺ depend on its salvage pathway. Here, the authors show that the NAD⁺ salvage pathway in hypothalamic astrocytes is activated to promote obesity in high fat diet-fed mice.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

XXXMicrotubules are nucleated in vivo by γ-tubulin complexes and comprise 13 protofilaments. How this precise geometry is controlled remains unclear. These authors report the cryo-electron microscopic structure of the universally conserved, core microtubule nucleating complex, _γ-tubulin small complex. The structure provides insight into how this complex establishes thirteen-fold tubulin symmetry.

Fankhauser et al. provide an in-depth review of preclinical mouse models used to study immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). They discuss potential improvements to the field that could, in the future, strengthen our understanding of ICI-myocarditis.

Minakuchi et al. find that separable inhibitory inputs to a critical hypothalamic aggression-control node can influence the evolution of an aggressive state by independently modulating either the motivational phase or the action phase.

Mutations in profilin 1 (PFN1), which modulates actin dynamics, are associated with ALS. Here the authors show that expression of ALS-PFN1 is sufficient to induce deficits in human microglia-like cells, including impaired phagocytosis and lipid metabolism, and that gain-of-function interactions between ALS-PFN1 and PI3P may underlie these deficits.

Limited tumor cell delivery is a major challenge for the efficacious delivery of siRNAs to silence traditionally undruggable oncogenes. Here the authors optimize siRNAs for in situ binding to albumin through C18 lipid modifications and show the application of the lead conjugate structure for targeting MCL1 in orthotopic breast tumors in mice.

Macrophages coordinate the disposal of apoptotic cells. Ajay Chawla and his colleagues show that PPAR-δ, a sensor of fatty acids, is involved in this process. Ingestion of apoptotic cells by macrophages prompts the upregulation of PPAR-δ, which then responds by enhancing the expression of opsonins. Lack of PPAR-δ reduces apoptotic cell clearance and predisposes to autoimmunity (pages 1246–1248).

Chun et al. find that a severe model of reactive astrocytes overproduces hydrogen peroxide, leading to the development of Alzheimer’s disease-like pathologies, including neurodegeneration, tauopathy and memory impairment.

Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

A comparative analysis of Cryptosporidium genome sequences elucidates the evolutionary history of these parasites and highlights changes associated with its human adaptation.

Co-administration of a whole-inactivated influenza virus (IAV) vaccine (γ-Flu) with a whole-inactivated Streptococcus pneumoniae vaccine (γ-PN) enhances IAV-specific immune responses due to the ability of γ-PN to directly interact with γ-Flu, thus increasing viral uptake by macrophages.

Defects affect the performance of photovoltaic devices, but their exact role is still under scrutiny. Luria et al. use 3D imaging of current pathways in a working CdTe solar cell with nanoscale resolution and observe electrically active defects, which contribute to conduction.

Profiling of over 38,000 CD34⁺ cells from patients with CALR-mutated myeloproliferative neoplasms, using the ‘Genotyping of Transcriptomes’ procedure, reveals that the transcriptional output of these mutations depends upon native cell identity.

Rationally designed polymer vesicles increase cytosolic delivery of cGAMP, activating the STING pathway and increasing the immunogenicity of the tumour microenvironment in in vivo murine models of melanoma and in human metastatic melanoma tissues.

A study developed genomic resources and efficient transformation in the orphan crop groundcherry, and managed to improve productivity traits by editing the orthologues of tomato domestication and improvement genes using CRISPR–Cas9.

Assembly of phased human genomes is achieved by combining long reads and long-range conformational data.

Translation Together, a transnational consortium of translational research organizations, reflects on successes and challenges in regional COVID-19 pandemic responses and proposes five priorities to improve preparedness for future global public health crises and improve the global approach to translational research and science.

Osteoporosis and bone fractures affect millions of patients worldwide and are often due to increased bone resorption. Here the authors identify the cytoplasmic protein ELMO1 as an important ‘signaling node’ promoting the bone resorption function of osteoclasts.

Despite, and perhaps because of, extensive data regarding agricultural variables and plant traits, finding connections to crop yields can be difficult to compile. Machine learning models detailed here can provide accurate predictions to tease out behaviours.

CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.

CTLA-4 is an important co-inhibitory receptor for T cells. Here, the authors show that CTLA-4 also has a function on B-1a cells, as conditional deletion results in activation of these cells and knockout mice develop an autoimmune profile.

Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.

Genetic variation can impact protein complexes and interaction networks, but reconciling genetic and proteomic information remains challenging. To address this need, the authors develop Genoppi —a computational tool for integrating genetics and cell-type-specific proteomics data.

CD11c⁺T-bet⁺ B cells have been linked with different autoimmune diseases, but targeting these cells has been challenging. Here the authors use an adenosine 2A receptor agonist to deplete these B cells and to inhibit or reverse autoimmune symptoms and pathology in mice.

Intergenerational preconditions and historical conferment of opportunity play a role in social mobility. This study considers the geography of relative deprivation to show how different family groups across Great Britain experience different intergenerational outcomes.

The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking Aβ fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.

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.

A new cryo-EM structure of the ~1 MDa Escherichia coli cellulose synthase macrocomplex reveals how cellulose biosynthesis and phosphoethanolamine (pEtN) modification are coupled to promote host-tissue adhesion.

RNA-sequencing experiments determine that sorbitol, a metabolite produced by the host enzyme aldose reductase, is exploited by Clostridium difficile in its adaptation to inflammatory conditions in the gut.

The extent of antibody protection against SARS-CoV-2 remains unclear. Here, using a cohort of 120 seroconverted individuals, the authors longitudinally characterize neutralization, Fc-function, and SARS-CoV-2 specific T cell responses, which they show to be prominent only in those subjects that elicited receptor-binding domain (RBD)-specific antibody titers above a certain threshold, suggesting that development of T cell responses to be related to anti-RBD Ab production.

Septoria tritici blotch (STB) is a devastating foliar disease affecting worldwide wheat production. Here, the authors report a cysteine-rich receptor-like kinase that can confer resistance to Zymoseptoria tritici, the pathogen that causes STB, and slow penetration and intercellular growth of the pathogen.

Pair correlation microscopy is used to show that the shape of a nanoparticle can affect the way it crosses various barriers inside a cell, and this ultimately determines the site at which the nanoparticle releases its drug payload.

The effect of plants on future extreme heat events under elevated carbon dioxide (CO₂) is unclear. Here, the authors show that CO₂ plant physiological effects lead to increases in heat waves within a suite of climate model simulations, suggesting that vegetated areas are at risk of increased heat extremes.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

The tidal disruption event AT2019dsg is probably associated with a high-energy neutrino, suggesting that such events can contribute to the cosmic neutrino flux. The electromagnetic emission is explained in terms of a central engine, a photosphere and an extended synchrotron-emitting outflow.

Triple negative breast cancer can be divided into additional subtypes. Here, using omics analyses, the authors show that in the mesenchymal subtype expression of MHC-1 is repressed and that this can be restored by using drugs that target subunits of the epigenetic modifier PRC2.

The weakest interactions of protein complexes are thought to be lost when such assemblies are removed from their natural, watery environments. Not so, reveals a study in the vacuum chamber of a mass spectrometer.

McCarthy, Kaeding et al. identify H3K9me3-heterochromatin proteins that repress heterochromatic genes with implications in hepatic reprogramming and show that ERH is key to global H3K9me3 maintenance in human cells.

Pyrochlore iridates lie at a tuning-free magnetic quantum critical point hosting several complex exotic phenomena. Here, the authors discover an electronic phase separation in single crystalline Pr₂Ir₂O₇, where well-defined Kondo resonances are interweaved with a non-magnetic metallic phase with Kondo-destruction.

In the cerebral cortex, information is processed by multiple hierarchically organized areas, reciprocally connected via feedforward and feedback circuits. Here the authors show that in primate visual cortex, feedforward projection neurons receive monosynaptic feedback contacts selectively from the area to which they project.