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Imc is a midbrain inhibitory nucleus essential for stimulus selection across space. Here, the authors show in the barn owl that global inhibitory surrounds of Imc neurons are constructed within Imc, but their classical inhibitory surrounds are inherited from inputs.

Chiolo and colleagues find that, in a SUMOylation-dependent manner, heterochromatic double-strand breaks move to the nuclear periphery where Rad51 is recruited to continue repair.

Broken chromosomes are lethal to cells with breaks ends often containing complex DNA damage. Here, the authors reveal a key role for the SNM1A enzyme in cleaning up break ends. Key anticancer drugs, and therapeutic radiation produce complex DNA breaks, making SNM1A an appealing therapeutic target.

The cell wall of Gram-positive bacteria consists of peptidoglycan modified with other polymers, such as the capsular polysaccharide. Here, the authors reconstitute the biosynthesis of capsular polysaccharide and elucidate its interplay with the cell wall biosynthetic machinery.

Cao et al. find that the mesenteric lymphatic system becomes dysfunctional during obesity in mice and humans, leading to visceral adipose tissue accumulation and insulin resistance.

Numerous proteins interact with the actin cytoskeleton, convoluting their influence on cellular behaviour. Here the authors engineer actin-binding switch tools that can be activated with external stimuli to control the activity of just one protein.

Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.

There is a need for potent and non-toxic estrogen receptor (ER) antagonists to overcome the limitations of existing endocrine therapies. Here the authors report the results from Arm 1 of the Phase 1/2 study (AMEERA-1) among postmenopausal women with ER+/HER2− advanced breast cancer, which evaluates the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of amcenestrant administered as monotherapy.

Reactive oxygen species (ROS) production by reverse electron transfer (RET) through complex I is thought to cause tissue damage from heart attacks. Here, the authors combine in vivo work with biochemical and cryo-EM analyses to characterize the effects of a P25L mutation in the ND6 subunit of mitochondrial complex I. They observe that this mutation does not affect oxidative phosphorylation but renders complex I unable to generate ROS by RET: ND6-P25L mice are protected against cardiac ischaemia–reperfusion injury, thus providing evidence for the proposed role of ROS production in myocardial infarction.

Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.

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.

CYP5122A1 is a sterol C4-methyl oxidase that catalyzes the sequential oxidation of lanosterol, is essential for both Leishmania donovani promastigotes in culture and intracellular amastigotes in infected mice, and provides a new target for antileishmanial drug discovery.

A structural look at the interaction between the SH3b domain of the peptidoglycan endopeptidase lysostaphin and the target for its antistaphylococcal activity, peptidoglycan, reveals a mechanism of bacterial cell wall binding.

Deep clinical phenotyping at 28–60 days post-discharge of patients who had been hospitalized with COVID-19 and subsequent long-term follow-up with electronic health records reveal evidence of persistent cardio-renal involvement.

RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.

Checkpoint blocking therapies are used to treat metastatic melanoma, but can have adverse immune-mediated effects, including liver pathology. Here the authors identify an expanded pool of CD4⁺ effector memory T cells resulting from prior CMV exposure as a risk factor for this adverse effect in these patients.

The tumour microenvironment provides signals to support leukaemic stem cells (LSC) maintenance and chemoresistance. Here, the authors show that disrupting niche-associated signalling by inhibiting receptor-mediated endocytosis with a dynamin GTPase inhibitor overcomes chemoresistance of LSC.

The pro-apoptotic BAX protein is a monomer under homeostatic conditions and, in response to stress, transforms into oligomers that induce apoptosis. Here, the authors characterize structural features of BAX that individually stabilize the monomer while collectively contributing to oligomerization.

The bacterial periplasmic predator Bdellovibrio bacteriovorus deacetylates the peptidoglycan of the prey bacterium early upon invasion. Here, the authors identify and characterize a Bdellovibrio lysozyme that acts specifically on deacetylated peptidoglycan and is important for periplasmic exit.

Placental inflammation is sometimes associated with health outcomes later in life. Here, the authors find that expression of genes associated with the homeostatic function of Hofbauer cells, a placenta-specific macrophage, are associated with protection from adult cardiovascular and depressive disorders

C-type lectins and SIGLEC1 function as attachment receptors for SARS-CoV-2 and enhance ACE2-mediated infection.

Small nucleolar ribonucleoprotein complexes (snoRNP) are fundamental for ribosome biogenesis. Here the authors provide insight into the 5ʹend processing of S. cerevisiae snoRNA and its important role in downstream nuclear events.

Tuz et al. report that stroke and myocardial infarction induce the release of neutrophil extracellular traps (NETs), triggering the loss of B cells and a decrease in immunoglobulin A secretion, and that inhibition of NETs prevents the loss of immunoglobulin A in mice and in patients with stroke.

Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.

Androgen receptor can promote tumour progression in desmoplastic small round cell tumour (DSRCT), an aggressive paediatric malignancy that predominantly affects young males. Here, the authors show that DSRCT is an AR-driven malignancy and sensitive to androgen deprivation therapy

The authors identify an impaired myelination signature from the brains of mouse models of Pitt–Hopkins syndrome and show that it is shared in the postmortem brains of people with autism.

mRNA therapeutics delivered via lipid nanoparticles are being developed for the treatment of metabolic diseases caused by protein deficiency. Here, the authors use preclinical data to develop translational PK/PD models, which scaled allometrically to humans to predict starting doses for first-in-human clinical studies for in propionic acidemia, methylmalonic acidemia, and phenylketonuria.

This study describes a method to insert large stretches of exogenous DNA into mammalian genomes, which is used to insert human ACE2 loci into mouse to produce a model of human SARS-CoV-2 infection.

An amplicon-based sequencing protocol that includes synthetic DNA spike-ins improves the quality and efficiency of SARS-CoV-2 high-throughput sequencing and detects common errors in genomic data.

The regulatory role of calcitonin in bone homeostasis is well studied, yet its molecular activity is poorly understood. The authors show that calcitonin regulates bone cells function by inhibiting the osteoclast secretion of sphingosine 1-phosphate, a lipid mediator of osteoclast–osteoblast crosstalk.

Studies of cell heterogeneity in white matter in primates have been limited to date. Here the authors describe a marmoset brain cell atlas that bridges rodent and human data, revealing strong gray-white matter glial segregation.

Grant Stewart, Andrew Jackson, Christopher Mathew, Fowzan Alkuraya and colleagues identify a novel replication fork protein, DONSON, which is important for maintaining genome stability. Mutations in DONSON cause microcephalic dwarfism and lead to stalled replication forks and DNA damage.

Authors present a comparative immunological characterisation of Chlamydia vaccine, CTH522/CAF®01, in mice and humans. Findings suggest the mouse to be a good predictor of human immunity to the Chlamydia vaccine CTH522/CAF®01, and long-lasting protection in the mouse further supports the development of this promising vaccine candidate.

Oligodendrocyte (OL) injury and loss is a pathologic hallmark of multiple sclerosis. Here, the authors show the presence of stress granules in OLs in multiple sclerosis lesions, and their in vitro studies in human OLs indicate that stress granules formation is a response to a combination of metabolic stress and pro-inflammatory conditions.

The microbiome in the uropygial gland and feathers of the bird Pachycephala schlegii has protective properties. Here, the authors report an Amycolatopsis species in this microbiome that produces antimicrobials including two novel compound families.

Fernández-Chacón et al. use imaging and scRNA-seq after targeting multiple Notch genes and angiogenic signaling pathways to find that the function of these pathways in vascular pathophysiology cannot be predicted by assessing transcriptional states.

The Aegilops tauschii-derived leaf rust resistance gene Lr42 has been widely used for breeding resistance wheat cultivars, but the molecular basis is unknown. Here, the authors show that Lr42 encodes an NLR-type of disease resistance gene by bulked segregant mapping in Ae. tauschii and confirm its function in common wheat.

In animal groups, the degree of alignment of individuals could have different benefits and costs for individuals depending on their reliance on private or social information. Here the authors show that in shoals of three-spined sticklebacks, some individuals reach resources faster when groups are disordered, a state which favours reliance on privately acquired information, while other individuals reach resources faster when groups are ordered, allowing them to exploit social information more effectively.

The process of protein crystallization is poorly understood and difficult to program through the primary sequence. Here the authors develop a computational approach to designing three-dimensional protein crystals with prespecified lattice architectures with high accuracy.

Deep learning models were used to design synthetic cell-type-specific enhancers that work in fruit fly brains and human cell lines, an approach that also provides insights into these gene regulatory elements.

ATRX inactivation occurs often in IDH-mutant gliomas and has been associated with immune dysfunction. Here, using preclinical models of glioma, the authors show that ATRX inactivation promotes innate immune signalling in response to double stranded RNA-based innate immune agonists, an effect that is masked in IDH-mutant tumours, presenting a therapeutic vulnerability.

Here the authors use positron emission tomography to visualize fibroblasts in patients with arthritis and combined with spatial transcriptomic data show that these cells undergo a phenotypic shift upon resolution of inflammation. A CD200⁺DKK3⁺ fibroblast subset promotes this resolution by inhibiting tumor necrosis factor and interleukin-17A.

Homotrimeric DARPin molecules neutralize SARS-CoV-2 variants of concern by targeting a critical ACE2-binding interface.

Antibiotics targeting cell wall synthesis display an unexplained gap between in vivo efficacy and in vitro binding affinity for their target. Here, Piepenbreier et al. develop a model for bacterial cell wall biosynthesis, show how it is affected by antibiotics, and use it to predict in vivo efficacy of antibiotics.

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.

Two Prevotella copri metagenome-assembled genomes that are positively associated with ponderal growth are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2—a microbiome-directed complementary food.

This work reveals a mechanism of cGAS- and STING-dependent type I IFN induction in response to biofilm-associated Candida albicans DNA packaged in extracellular vesicles.

Heterologous vaccination regimens for COVID-19 could be useful for example if there is a shortage of one vaccine type. Here, Spencer et al. show that heterologous vaccination with a self-amplifying RNA vaccine and an adenoviral vectored vaccine performs at least as well as the homologous vaccinations in mice.