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Here, Hachfi et al show how spores of the enteropathogenic Bacillus cereus bacteria escape host innate immune responses in the intestine to favour bacterial persistence.

Prostaglandin E2 from the tumour microenvironment impairs interleukin-2 sensing by tumour-infiltrating lymphocytes, restricting proliferative response and promoting T cell death via metabolic impairment and ferroptosis. 

Carcinoma subtypes are normally linked to specific genetic alterations, but tissue mechanical changes also play a role. Now, aberrant morphologies resembling bladder carcinoma are shown to emerge from stiffness changes during epithelial overgrowth.

As part of the SWEETSTONE trial, the authors report the ability of the sodium-glucose cotransporter 2 inhibitor empagliflozin to reduce the likelihood of kidney stone formation in individuals without diabetes.

How diffusible signals determine cell fate is a vital and still unresolved developmental biology issue. Using the Drosophilaegg chamber as a model system, here the authors apply novel imaging and mathematical approaches to show that cell differentiation depends on irregular tissue domains that lead to asymmetric distributions of morphogens.

Resonant absorption of light in atoms can lead to autoionization, whose probability exhibits a Fano intensity profile. Here, the authors use attosecond pulses and weak infrared radiation to study the phase variation of the photoionization amplitude across an autoionization resonance in argon.

A study describes the molecular basis of sexual development of Toxoplasma gondii entirely in vitro, demonstrating the role and interaction of AP2XII-1 and AP2XI-2 in the developmental program of this protozoan parasite.

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.

EGFRvIII-targeted CAR T cells have been proposed as a therapeutic option for patients with glioblastoma (GBM), however, clinical responses remain suboptimal. Here the authors engineer anti-EGFRvIII CAR T cells to secrete an optimized SIRPγ-derived CD47 blocker, showing that combining CAR T cell effector functions with enhanced macrophage-mediated tumor cell phagocytosis improves anti-tumor efficacy in preclinical models.

A paramutation occurs between two alleles in the same locus, when one allele induces a heritable mutation in another allele without modifying the DNA sequence; now, in Drosophila, a paramutation is shown to be transmissible over generations.

Jean-Pierre Bourquin, Martin Stanulla and colleagues report whole genome, whole exome and transcriptome sequencing of TCF3-HLF fusion–positive acute lymphoblastic leukemia. Drug response profiling in patient-derived xenografts identified sensitivity to the BCL2-specific inhibitor ABT-199 (venetoclax) as a new option for treating this fatal disease.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

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.

Here the authors describe a fluorescent lipid droplet reporter mouse, which allows the staining-free detection of these important lipid-storing organelles. Using this model, they show that LDs are highly abundant in the developing and adult brain.

Current treatments for age-related neovascular macular degeneration (nAMD) suffer from limited efficacy. Here, Zhao et al. show that pharmacological inhibition or genetic deletion of the mineralocorticoid receptor (MR) limits choroidal neovascularisation in rodents, and show in a pilot clinical study that targeting the MR pathway may provide clinical benefits in nAMD patiens.

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.

Wearable smart devices often have green light diodes to monitor health. Here the authors use this to control a light-activated genetic switch for GLP1 production in diabetic mice.

Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.

The mechanism by which ingested material accesses the cytosol for cross-presentation is unclear. Caetano Reis e Sousa and colleagues demonstrate that signaling via the lectin receptor DNGR-1 ruptures the phagosome and releases its contents to the cytosol for cross-presentation.

GLP-1 is an incretin hormone and neuromodulator produced by gut enterocytes and CNS neurons. Brierley et al. find that GLP-1 from peripheral and central sources acts independently through distinct gut–brain circuits to suppress eating.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

How hormonal signaling in the mammary epithelium controls the surrounding extracellular matrix is unclear. Here, the authors show that a secreted protease, Adamts18, induced by upstream estrogen-progesterone activated Wnt4 in myoepithelial cells, remodels the basement membrane and contributes to mammary epithelial stemness.

Microtubules carry patterns of post-translational modifications that are important for the regulation of key cellular processes. Now a semi-synthetic method facilitates the production of tubulins with defined post-translational modifications. Using these designer tubulins, polyglutamylation of α-tubulin is found to promote its detyrosination by enhancing the activity of the carboxypeptidase vasohibin/small vasohibin-binding protein.

In vertebrate vision, the two types of photoreceptors, rods and cones, operate under low and bright light intensities, respectively. Here the authors show that under bright light conditions, when rods are not sensing light, they act as relay cells for cone-driven surround inhibition.

The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K.

In mouse models of breast cancer, anti-CCL2 therapy—thought to be potentially useful in treating cancer—is shown to accelerate the growth of lung metastases on discontinuation due to a surge of recruitment of bone marrow monocytes and increased interleukin-6-dependent vascularization of the lung metastatic environment.

Microtubules are acetylated on the inside of their hollow lumen, a modification linked to their lifespan. Here, the authors show that damage holes act as entry points for a deacetylase to access the lumen, thereby locally counteracting acetylation.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

Steroid-refractory acute graft-versus-host disease (aGVHD) is associated with a low one-year survival rate. Here, the authors show that ROCK1 is upregulated in leukocytes from patients with steroid-refractory aGVHD and that ROCK1/2 inhibition reduces the severity of aGVHD in mice by interfering with activation of multiple immune cell types.

MRI data from over 1000 participants between the ages of 46 and 87 reveals that cardiovascular risk factors are associated with myelin loss and neuroinflammation in the brain

Restoring oxygenation in hypoxic tumors might lead to favorable oncological outcome of patients if combined with standard multimodal therapy regimens. Here the authors report a phase Ib clinical trial of anti-hypoxic myo-inositol trispyrophosphate (ITPP) in hepato-pancreato-biliary neoplasms.

The DR isotype of the human leukocyte antigen of the MHC class II—or its homologues in bats, pigs, mice and chickens—is an essential cell entry determinant for bat influenza A viruses.

The molecular mechanisms underlying cardiac chamber formation are not well understood. Here, the authors show that planar cell polarity signalling through Wnt5b and Wnt11 coordinates localised and tissue-scale polarised actomyosin contractility in the zebrafish heart, regulating cardiac chamber formation and looping.

Analysis of sedimentary DNA from ten European lakes reveals that over the past 100 years cyanobacterial communities have become compositionally and phylogenetically more similar, in line with homogenization of lake environmental conditions.