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RAS-driven cancers depend on SHOC2–PP1C. Here, the authors reveal that KRAS forms a low-affinity SHOC2–PP1C complex with fewer contacts than MRAS and show that dual inhibition of KRAS- and MRAS-dependent assemblies strengthens SHOC2 suppression and may overcome resistance.

Peripartum cardiomyopathy (PPCM) is a potentially fatal heart condition with poorly understood molecular causes. Here, the authors show that loss of the protein PTRH2 in female mice leads to postpartum heart failure, identifying it as a potential therapeutic target.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

In this work, authors demonstrate programmable nanostructures using two-dimensional materials for nanoscale liquid manipulation. The nanoswitches and capsules can hold zeptoliter liquid volumes, enabling active nanofluidics circuits and confined reactors.

How changes in brain blood vessels lead to a chronic reduction in blood flow and, consequently, to vascular dementia is poorly understood. Here, the authors show that venous endothelial dysfunction driven by EPAS1 promotes abnormal vascular remodeling and contributes to cognitive decline.

This study shows that maternal and perinatal obesity cause bronchial and vascular smooth muscle cell proliferation through an IL-6-FoxO1 axis, and favor thereby the emergence of bronchial obstruction and pulmonary hypertension later in life.

Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are efficacious in the context of colorectal cancer.

Maier et al. show that metacognitive learning from consequences can shape moral decision-making.

The authors demonstrate nano-engineered thin film thermoelectric materials are attractive for practical solid-state refrigeration with semiconductor manufacturing and ultra-low 0.003-cc materials usage.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Haematopoietic stem/progenitor cells (HSPCs) transform from aortic endothelium into migratory cells that move through stroma and enter circulation to colonize haematopoietic tissues. Here the authors show that HSPCs' passage is facilitated by primitive macrophages that secrete extracellular matrix-degrading enzymes.

A retrainable deep learning software allows to segment hearts and diagnose congenital heart disease in micro-computed tomography images of mouse models.

Using in vivo two-photon imaging, Berthiaume et al. demonstrate how pericyte loss during aging could contribute to deterioration of cerebral blood flow. They also show how pericyte remodeling reduces the deleterious effects of pericyte loss.

Male offspring of pregnant mice infected with a low dose of Zika virus infection have increased testosterone levels, an increased number of immature neurons in apical hippocampal dendrites and are less likely to survive in utero infection than female littermates.

CRISPR-Cas9 is an adaptive immune system that protects bacteria against invading DNA. Here, the authors show that the master virulence regulator CovR controls the CRISPR-Cas9 system in Streptococcus agalactiae, allowing transient increases in Cas9 off-target activity to overcome escape mutations in the target DNA, boost immune memory recall, and promote new memory acquisition.

This study presents an experimental system to conditionally immortalize murine megakaryocyte-erythroid progenitor cells, providing a versatile system for investigation of red blood cell and platelet biology in vitro and in vivo.

Alzheimer’s Disease (AD) is commonly preceded by a prodromal period. Here, the authors report the presence of large plasma Aβ aggregates from patients with mild cognitive impairment, which associate with low level AD-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes.

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.

Zuhra and Petrosino et al. report evidence that cyanide acts as a regulatory gasotransmitter in mammalian cells, where it is shown to affect cellular bioenergetics, most likely via protein S-cyanylation.

Glacierized regions that are projected to become ice-free in this century could provide substantial water storage and hydroelectric power, according to this worldwide theoretical assessment.

Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets

The median eminence (ME) at the base of the brain controls body homeostasis. Here, the authors describe a functional tanycyte subpopulation at the ME which tastes the surrounding milieu, responds to metabolic signals and regulates glucose homeostasis.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

The beneficial effects of exercise on cardiovascular disease are linked to decreased inflammation through crosstalk between adipose tissue and hematopoietic progenitor cells in the bone marrow.

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.

The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

Arterial macrophages develop from either yolk sac or bone marrow progenitors. Here, the author show that ageing-induced reduction of arterial macrophages is not replenished by bone marrow-derived cells, but under inflammatory conditions circulating monocytes are recruited to maintain homeostasis, while arterial macrophages of yolk sac origin carry out tissue repair.

In-person and online conferences each have their benefits, with hybrid conferences intended to blend the best of both worlds. But do hybrid conferences fulfil the promise? Fifteen attendees across three global conferences share their collective experiences.

The authors show that in the halophyte Salicornia the sodium transporter SOS1 localizes to the tonoplast, likely storing sodium in the vacuole. The intrinsically disordered protein SALTY, increases yeast salt tolerance possibly stabilizing ribosomes in the ER.

Yvernogeau, Gautier, Petit et al. demonstrate the existence of a haemogenic endothelium capable of de novo haematopoietic stem and progenitor cell generation in the forming bone marrow of chicken and mouse fetuses and newborns.

Exercise has beneficial effects on cognition. Here, authors utilize an exercise model to show ACVR1C to be an essential bidirectional regulator of memory and synaptic plasticity in adult, aging and 5xFAD mice beyond the context of exercise.

Phenotypic and functional plasticity of macrophages is implicated in the pathophysiology of numerous autoimmune rheumatic diseases. In this Review, the authors discuss the latest insights into this complex and dynamic process and the potential implications for the treatment of these diseases.

Batlle and colleagues develop an organoid platform for functional antibody screening and identify a therapeutic bispecific antibody that binds EGFR and LGR5 and that shows efficacy across epithelial tumor patient-derived xenograft models in vivo.

Beta II protein kinase C (βIIPKC) activation contributes to heart failure. Here the authors show, in a rat model of myocardial infarction, that heart failure outcome can be improved by selectively inhibiting the interaction between βIIPKC and its downstream mitochondrial target Mitofusin-1, and that this strategy is superior to global βIIPKC inhibition.

The retrosplenial cortex and superior colliculus of mouse form a neural circuit that specifically encodes shelter location, facilitating rapid escape from predatory threats.

The extrusion of large extracellular vesicles is an important mechanism that facilitates cell-to-cell communication and maintains homoeostasis. Here, Atkin-Smith et al. use intravital microscopy to directly visualize the formation of large extracellular vesicles in bone marrow.

GABA is an important neurotransmitter in animals, and while it accumulates in plants under stress, its potential role in plant signalling was poorly understood. Here, Rameshet al. show that GABA rapidly alters the activity of plant ALMT anion channels modifying root growth and stress tolerance.

Assessing tumour microenvironment-targeted drug candidates remains challenging. Here, the authors develop a comprehensive screening platform that allows for monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumour spheroids.

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. Here, Li et al. reveal a morphological cell expansion wave behaviour that coordinates epithelial flattening and tissue elongation during Drosophila oogenesis.

Dopamine in the ventral striatum conveys a complex reward-associated signal. This study demonstrates how dopamine reflects sustained reward availability, and rapidly signals unexpected changes in availability.

Gq proteins are one of four major classes of G proteins; optogenetic receptors for selective and repetitive activation of Gq proteins with fast kinetics are lacking. Here the authors report UV light-dependent Gq signalling using human Neuropsin (hOPN5) and demonstrate its potential as an optogenetic tool.

Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.