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Curved cell shapes are common among bacteria, but the underlying morphogenetic mechanisms are incompletely understood. Here, the authors identify an outer-membrane protein complex that promotes cell curvature in Rhodospirillum rubrum by forming helical ribbon structures that modulate the dynamics of cell wall biosynthesis, biasing cell growth towards the cell’s outer curve.

Retinal vein occlusion can cause blindness, and features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here the authors report a non-apoptotic role of endothelial caspase-9 in regulating blood-retina barrier integrity and neuronal survival, which can be therapeutically targeted in a mouse model of retinal vein occlusion.

Life-threatening vascular tumors can be associated with uncontrolled activity of the guanine nucleotide-binding protein subunit alpha (Gαq). Here, the authors develop a murine model for these tumors and show that MEK inhibition prevents formation of vascular lesions and improves survival.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

Neutrophils infiltrate glioblastomas with the capacity to engage pro/anti tumoural responses. Here the authors developed proteomic workflows to stratify neutrophil heterogeneity by function. This work provides a platform to study neutrophil proteomes with single cell resolution in glioblastoma.

Sarcolipin is an inhibitor of the ATP dependent calcium pump SERCA, and is abnormally elevated in Duchenne muscular dystrophy. The authors show that reducing sarcolipin expression ameliorates skeletal muscle pathology and cardiomyopathy and extends life span in mouse models of DMD.

Allosteric modulation is crucial in metabolic regulation but unexplored in gut microbehost interactions. Here the authors show gut microbe-derived phenylacetylglutamine acts as a negative allosteric modulator of β2-adrenergic receptors, impacting heart function.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

Roy et al. quantify the impact of a high-fat diet across genetically diverse strains of mice, revealing a generally negative effect on lifespan but also a wide variability.

Human activities affect marine predators in complex ways, yet we lack spatial understanding of cumulative impacts across key habitats. Here the authors analyse distribution and movements of eight marine predators, and find that species and human impacts vary across space and overlap within marine sanctuaries.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Triple negative breast cancers (TNBC) disseminate and metastasise, but the clonal relationship of metastases to primary tumours is poorly understood. Here, the authors use cellular barcoding of TNBC patient-derived xenografts and track the fate of barcoded clones in primary tumours and their metastases, including after resection or chemotherapy.

Yang and colleagues report that increased extracellular matrix stiffness promotes nuclear localization of Twist1 to drive epithelial–mesenchymal transition, cancer cell invasion and metastasis.

By comparing the genome-wide profile of H4K16ac in AD with younger and elder controls, the authors propose a mechanism for how age is a risk factor for AD: a histone modification, whose accumulation is associated with aging, is dysregulated in AD.

Magnetic palaeointensity data from the Barberton Greenstone Belt (South Africa) as well as the Jack Hills (Western Australia) show nearly constant palaeofield values between 3.9 Ga and 3.4 Ga, providing evidence for stagnant-lid mantle convection.

Sick heart and vessels skew hematopoiesis toward inflammatory myeloid cells. Rhode et al. show that hypertension, atherosclerosis and myocardial infarction cause endothelial dysfunction in bone marrow (BM), which in return causes overproduction of inflammatory myeloid cells and systemic leukocytosis in mice. This process is mediated by VEGF signaling, IL-6 and versican production by the BM endothelium.

Gene signatures that predict response to immune checkpoint blockade (ICB) therapies in melanoma have been based on preclinical models and pre-treatment samples. Here the authors develop pathway-based signatures to predict ICB response in melanoma using on-treatment samples, leading to improved performance.

Though endocytosed dietary cholesterol is transferred to the endoplasmic reticulum (ER), how this is regulated is unclear. Here, the authors report a role for Niemann-Pick Type C Protein 1 (NPC1) in tethering endocytic organelles to the ER, which may contribute to interorganelle cholesterol transport.

Biosynthesis of all androgens from cholesterol first requires cytochrome P450 (CYP) 11A1 for generation of pregnanes and then CYP17A1 for biosynthesis of androgens, but CYP17A1 inhibition cannot completely inhibit androgen biosynthesis in prostate cancer. Here, the authors identify a role for CYP51A1 in the biosynthesis of androgens that completely bypasses the requirement for CYP17A1 and demonstrate that CYP51A1 is essential for the biosynthesis of ¹³C-testosterone from ¹³C-cholesterol in prostate cancer cells.

Francis et al. used cryo-electron microscopy to show how a SPIN90 dimer activates the metazoan Arp2/3 complex to nucleate linear actin filaments for unidirectional and bidirectional growth, forming potential scaffolds for rapid assembly of dynamic actin networks.

The outflow pathway of cerebrospinal fluid into lymph nodes in the neck and how non-invasive mechanical stimulation can enhance drainage and restore impaired outflow in aged mice are explored.

A recombinant antivenom composed of eight nanobodies provides broad protection against venom-induced lethality and dermonecrosis in mice challenged with venoms from cobras, mambas and rinkhals snakes.

Multimodal nanosensors have been developed to target and respond to hallmarks in the tumour microenvironment and provide both a non-invasive urinary monitoring tool and an on-demand positron emission tomography imaging agent to localize tumour metastasis and assess response to therapy.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Methyl-CpG-binding protein 2 (MeCP2) is phosphorylated in neurons in response to neuronal activity. Here, Li et al.show that it is also phosphorylated by aurora kinase B in neural progenitor cells, and cell cycle-dependent phosphorylation of MeCP2 regulates the balance between proliferation and differentiation via Notch signalling.

The neural mechanisms driving seizure development in peritumoral brain regions remain incompletely defined. Here, using patient tissue, glioma mouse model, and computational simulation, the authors identify early pathological activities that are predictive of tumor-associated seizures.

A new strategy that uses prime editing to convert an endogenous tRNA into a suppressor tRNA shows therapeutic potential for multiple genetic diseases that are caused by premature stop codons.

Childhood neuroblastoma can be separated into high and low risk groups, with prognosis depending on age at diagnosis. Here, the authors show that low and high risk neuroblastoma tumours are composed of different cell types with different malignancy potential.

The existence of phosphatases specialized in regulating the axon initial segment (AIS) was unclear. Here, the authors show that a PP2A-B55 subunit is selectively enriched at the AIS and contributes to its local phospho-regulation.

Targetable delivery vectors for genetic cargo are needed. Here the authors report a modular platform with separate fusion and targeting components—Delivery to Intended REcipient Cells Through Envelope Design (DIRECTED)—and show cell type-specific delivery.

Here, Fry and colleagues examine the impact of antigen experience on subsequent CD8⁺ CAR T cell activity during the antileukemia response and show that RUNX2 overexpression enhances antitumor activity of these cells.

Cancer cells rely on macropinocytosis to survive in a nutrient-deprived environment. Here, Lambies et al. identified various members of the cell polarity protein network as essential regulators of macropinocytosis in a context of metabolic stress.

By increasing NAD⁺ consumption in various organelles, mitochondria are revealed to act as buffers that help maintain subcellular NAD⁺ levels. At the same time, cells are found to be particularly sensitive to a decline in NAD⁺ levels originating from mitochondria themselves.

Adjuvants are an important component of modern vaccines. Here, the authors employ a phenotypic screen of ~200k compounds and identify PVP-057, a TLR3 agonist with a simple scalable 3-step synthesis, as an adjuvant that induces durable humoral and cellular immunity to varicella-zoster virus (VZV) gE in mice.

Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 or TSC2 genes, which negatively regulate mTORC1 signalling. Here the authors selectively delete Tsc1 from dopamine neurons in mice and find impairments in striatal dopamine release that are sufficient to reduce cognitive flexibility.

During the Last Glacial Maximum, the deep Northwest Atlantic was only about 2 °C colder than today, suggesting sustained production of relatively warm North Atlantic Deep Water during the Last Glacial Maximum.

The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

Fungi produce oxygenated fatty acids, or oxylipins, of unclear function. Here, Niu et al. show that an Aspergillus oxylipin induces various developmental processes in several fungi, including lateral branching in human pathogenic Aspergillus species, and appressorium formation in the plant pathogen Magnaporthe grisea.

Whilst estrogen is known to be tumorigenic in some breast cancer, in some contexts it can be protective against invasion and dissemination. Here, the authors show estrogen can promote generation of Suppressive Cortical Actin Bundles that can inhibit motility dynamics through EVL-mediated actin cytoskeletal remodeling.

Tan et al. identify PRDM16 as a key repressor of fibrotic switching in smooth muscle cells and show that its downregulation in atherosclerosis drives smooth muscle cells toward a synthetic fate, promoting fibrous plaques.

Self-renewing cells play an important role in initiation, progression, and therapy resistance in glioblastoma. Here, the authors identify histone variant macroH2A2 as a regulator of chromatin organisation resulting in the suppression of transcriptional programs of self-renewal in glioblastoma.

Human mutations in PCYT2 result in severe pathology with failure to thrive and progressive degenerative disease. Cikes et al. demonstrate that loss of PCYT2-synthesized phosphatidylethanolamines in muscle impairs sarcolemmal lipid bilayer stability and mitochondrial homeostasis, leading to muscle degeneration and premature ageing in mice.

Using differences among strains as a model for inter-individual variation, this paper identifies a conserved metabolicadaptation in C. elegans that compensates for genetic variation.