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Cell surface receptors perceive immunogenic elicitors, triggering downstream signalling via receptor-like cytoplasmic kinases such as BIK1. Here the authors define and use the phosphorylation motif of BIK1 to find novel substrate candidates.

MultiCell is a deep learning method to capture complex cell dynamics during multicellular development.

Through next-generation spectral analysis, scientists have uncovered an evolutionary path for Wolf–Rayet stars in metal-poor environments. Characterized by hard ionizing radiation, these stars challenge current assumptions about massive star evolution.

COVID-19 has caused many healthcare systems to become overwhelmed, potentially impacting patient care. Here, the authors show that COVID-19-related in-hospital mortality rates in Israel increased in periods of moderate or high hospital load, independent of patient characteristics.

The mechanisms of pathological astrocyte responses during multiple sclerosis remain unclear. Kadowaki et al. found in MS mouse models that CLEC16A suppresses astrocyte pathogenic activities related to mitochondria by boosting mitophagy.

Squidiff is a diffusion-based model to predict transcriptomic changes in response to perturbations.

Longevity research aims to extend lifespan and reduce sickspan in aging. Here, the authors show that only interventions that steepen survival curves can compress the sickspan relative to lifespan.

A first-in-class fluorescence lifetime-based FRET sensor for phosphatase and tensin homolog (PTEN) enables the dynamic monitoring of PTEN activity in cultured cells and in vivo with high spatiotemporal resolution.

Notch signalling in endothelial cells of the bone induces change in the capillaries and mesenchymal stem cells of the environment to support haematopoietic stem cell amplification.

Protein imaging is multiplexed using combinatorial staining and deep learning decompression.

Advances in 3D neuronal cultures have allowed unprecedented access to the mechanisms underlying brain diseases. This work describes the novel Modular Neuronal Network (MoNNet) system, which enables more complex studies of cortical neuronal ensemble dynamics.

The direct contribution of aberrant epithelial cells to lung fibrosis is largely unknown. The authors use murine and human systems to identify how these cells activate fibroblasts, and how reciprocal signals cause them to enter a profibrotic state.

Majewska et al. show that p16-expressing senescent cells enhance the stability of the immune checkpoint PD-L1 by downregulating its proteasome-mediated ubiquitin-dependent degradation, leading to their accumulation in ageing and chronic inflammation.

A light-sheet fluorescence microscope leveraging consumer-grade components as well as optimized optics and software facilitates the high-resolution imaging of cleared and living samples at scale with lower costs.

Itkin et al. identify a role for Fli-1 in hematopoietic stem cell activation during regenerative hematopoiesis. They show that Fli-1 coordinates hematopoietic stem cells to stimulate niche-derived Notch1 feedback signals for demand-needed hematopoietic cell output.

The tumor microenvironment (TME) is complex and heterogenous, with cancer cells and diverse non-malignant cells interacting with each other. Here the authors define the network of interactions between different cell types in the TME of breast cancer, identifying and characterizing a two-cell circuit of cancer associated fibroblasts and macrophages.

A retrospective analysis of data from the Israeli Ministry of Health collected between 28 August 2020 and 24 February 2021 documents the real-life effect of a national vaccination campaign on the pandemic dynamics.

The two zygote centrioles are paternally inherited; however, their development is incompletely understood. Here, the authors show that the distal centriole is remodeled into an atypical centriole which functions as the zygote’s second centriole.

PIC-seq characterizes cellular crosstalk by sorting and sequencing physically interacting cells.

Zhang et al. uncover different dynamics underlying the maintenance and regulation of H3K9me3-enriched heterochromatin domains in mouse embryonic stem cells and propose that loss of H3K9me3 occurs through two distinct dynamic modes: passive dilution and active removal.

Maladaptive immunity negatively impacts Alzheimer’s disease (AD). Here, the authors show dysfunctional CD38-expressing CD4⁺ T cells in individuals with familial AD before symptom onset. Targeting CD38 in an AD mouse model restored metabolic fitness, improved cognition, and modified meningeal immunity.

Young children frequently encounter respiratory pathogens that elicit immune responses in developing lungs. Farber and colleagues examine rare lung tissue samples obtained from pediatric organ donors and find age-dependent formation of bronchus-associated lymphoid tissue (BALT), which peaks at 3 years of age and dissipates thereafter. Profiling of BALT lymphocytes indicates that repertoire and functional differences exist between the lung, draining lymph nodes and circulating cells.

Brachyurans, or crabs, are of commercial and ecological importance, but limited genomic resources exist. Here the authors present a chromosome-level genome and expression data for the Chinese mitten crab, to shed light on the biology of this group.

AlphaFold2 has originally been developed to provide highly accurate predictions of protein monomer structures. Here, the authors present a simple adaptation of AlphaFold2 that enables structural modeling of peptide–protein complexes, and explore the underlying mechanisms and limitations of this approach.

Phosphoproteomics data analysis is limited by poor phosphosite annotation. Here, the authors use machine learning with pan-cancer data to build a co-regulation network of phosphosites and a model for predicting kinase-substrate associations, providing a framework for systematic data interpretation.

People can track a limited number of moving items in perception, but it is unknown if similar limits apply to the imagination. The authors show the mental simulation of moving objects is a serial process, which advances only one object at a time.

Measuring metabolic fluxes in cellular compartments is a challenge. Here, the authors introduce an approach to infer fluxes in mitochondria and cytosol, and find that IDH1 is the major producer of cytosolic citrate in HeLa cells and that in SDH- deficient cells citrate synthase functions in reverse.

Gannot et al. show that Tac1 neurons in the NTS mediate an airway–vagal–brain pathway that is crucial for coughing in mice. These neurons receive direct vagal sensory inputs and coordinate downstream circuits to control coughing.

Centrioles are ancient organelles with a conserved architecture and their rigidity is thought to restrict microtubule sliding. Here authors show that, in mammalian sperm, the atypical distal centriole and its surrounding atypical pericentriolar matrix form a dynamic basal complex that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking.

Here, the authors identify a novel regulator of autophagy, skeletal muscle mass and integrity named MYTHO. Silencing MYTHO protects against muscle atrophy in a wide range of acute catabolic conditions, while prolonged silencing causes a severe myopathy.

Vaccination with multiple doses has been proven effective against severe COVID-19, but protection levels widely vary among individuals. This study examines the serological and immunological profiles in recipients of multiple doses of Pfizer BNT162b2 vaccine for immune markers that correlate with protection against and susceptibility for SARS-CoV-2 infection.

The authors use a series of self-finding games—wherein players must identify themselves when there are multiple potential candidates—to show that humans are near optimal at self-orienting, whereas popular reinforcement learning algorithms are not.

Shen et al. show that FMRP promotes mitochondrial fusion through HTT. FMRP loss caused fragmented mitochondria and oxidative stress in immature neurons, and enhancing mitochondrial fusion rescued neuronal and behavioral deficits in Fmr1-mutant mice.

Here, the authors generate a replication-competent VSV based vaccine expressing SARS-CoV-2 spike protein and show protection in the hamster model with one dose. Analysis of the antibody response in mice shows induction of neutralizing antibodies and suggests a desirable Th1-biased response to the vaccine.

Optimizing approach-avoidance behavior calls for neural encoding of related motivation outcomes. Here, the authors show that behavioral choice under conflict relies on differential neuronal firing patterns after punishment, in which mPFC neurons decode the outcome’s value and MTL neurons follow by reducing subsequent approach.

A computational pipeline identifies tumor antigen post-translational modifications guiding immune responses.

The use of lung and colonic organoid systems to assess the susceptibility of lung and gut cells to SARS-CoV-2 and to screen FDA-approved drugs that have antiviral activity against SARS-CoV-2 is demonstrated.

Gomez-Salinero, Itkin et al. demonstrate the cooperative role of two ETS transcriptor factors, ERG and Fli1, in the active maintenance of endothelial cell homeostatic function. Loss of these two genes in adult mice leads to multi-organ failure, hyperinflammation, systemic thrombosis and death. In vitro, expression of both ERG and FLI1 induces human adult non-vascular mesenchymal stromal cells to acquire endothelial-like properties. In humans, several cardiovascular disorders and inflammatory-related diseases are linked to mutations in both genes.

Bone marrow endothelial cells have dual roles in the regulation of haematopoietic stem cell maintenance and in the trafficking of blood cells between the bone marrow and the blood circulatory system; this study shows that these different functions are regulated by distinct types of endothelial blood vessels with different permeability properties, affecting the metabolic state of their neighbouring stem cells.

Zeta inhibitory peptide (ZIP) impairs the maintenance of acquired memories. ZIP is known as an inhibitor of PKMζ. Here, the authors unveil how ZIP impairs memory maintenance acting as an arginine donor, facilitating NO-dependent down-regulation of AMPARs, independently of its action on PKMζ.

Flow-injection mass spectrometry (FI-MS) enables high-throughput metabolomic profiling, but ion overload typically limits its sensitivity. Here, the authors show rapid and highly sensitive FI-MS overcoming an overload of the Orbitrap by analyzing sample-specific ion distributions.

A first-in-class covalent inhibitor of creatine phosphagen energetics was developed that induced toxicity in creatine kinase-dependent AML cell lines and regulated proinflammatory cytokine production in macrophages.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

Carbon-containing particulates accumulate with age in a subset of macrophages in human lung-associated lymph nodes, decrease macrophage phagocytic capacity and turnover and disrupt lymphoid tissue structure, potentially compromising adaptive immune responses.

In an experimental autoimmune encephalomyelitis model in mice, a subset of astrocytes retains an epigenetically regulated memory of past inflammation, causing exacerbated inflammation upon subsequent rechallenge.

Natural killer cells infiltrate the pancreas during type 1 diabetes. Mandelboim and co-workers find that the natural killer receptor NKp46 recognizes ligands on pancreatic beta cells and is essential for full diabetes development.

The mitochondrial network expands to accommodate cell growth, but how scaling occurs is unclear. Here, the authors show in C. elegans that ATFS-1 mitochondrial import is reduced when mitochondrial proteins are highly expressed, activating the unfolded protein response and causing expansion.

Alzheimer’s disease is characterized by progressive dementia and amyloid beta plaque deposition. Here the authors show in three relevant transgenic animal models that accumulation of activated B cells is central to AD pathology and depletion of B cells interferes with both histological and behavioural manifestations of the disease.