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How neurons form synapses is central to brain development. Here, the authors show that astrocytes can limit neuronal morphogenesis by secreting S100A6, which reduces protein turnover in neurons through calcyclin-binding protein mediated signaling.

The function of transient neuropeptides in developmental roles in the nervous system remains elusive. Here, authors demonstrate that galanin shapes synaptic wiring in the whisker pathway, a fundamental sensory modality for infant rodents before eye opening.

Póti et al developed cyclic, tuneable and chiral warheads against the protein-protein interaction surface of mitogen-activated protein kinases, which form a reversible covalent bond with nucleophilic surface residues to modulate cellular signaling networks.

Asymmetric hydrophosphorylation of unsaturated compounds is a straightforward and atom-economic approach to obtaining chiral organophosphorus compounds. Herein, the authors describe a Pd-catalzyed ligand controlled regiodivergent and enantioselective hydrophosphorylation of styrenes.

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during cancer progression.

Species’ range shifts projections are usually based on climate and land cover variables. Here, the authors use long-term records for bird species to show that species distribution models accounting for climate and land cover often fail to predict observed range shifts.

Inflammatory cell recruitment to injured tissues is needed for repair, but an excessive inflammatory response can exacerbate injury. Tibor Kempf et al. now identify the cytokine GDF-15 as a new anti-inflammatory factor that dampens leukocyte recruitment in the setting of myocardial infarction in mice, thereby preventing cardiac rupture. GDF-15 blocks leukocyte extravasation from the blood into injured tissue by inhibiting the activation of cell surface integrin receptors.

Single-cell RNA sequencing reveals molecular determinants of the developmental programs that orchestrate the intermingling of neuronal subtypes in the hypothalamus.

The authors show that brain inflammation in COVID-19 correlates with viral load, systemic inflammation and virus-sensing pattern recognition receptors. Microglial dysfunction occurs at sites of vascular inflammation with myelin injury and synapse loss.

Heart failure with preserved ejection fraction (HFpEF), which can be driven by obesity and hypertension, has a high prevalence but limited treatment options. Here, the authors show that nitro-oleic acid restores mitochondrial function and improves heart failure symptoms in a mouse model of HFpEF.

Patch-seq reveals new neuronal subtypes by combining electrophysiological and RNA-seq data on single neurons in situ.

Early life stress can induce lasting changes in brain function and behavior. Here, authors show that glutamatergic FKBP51 specifically in females mediates adaptive stress effects on anxiety and cognition via TCF4.

E. coli phage SU10 has a short non-contractile tail. Here, the authors show that after cell binding, nozzle proteins and tail fibers of SU10 change conformation to form a nozzle that enables the delivery of the phage DNA into the bacterial cytoplasm.

LSD1-CoREST-HDAC1/2 complexes are degraded by both the drug UM171 and cancer-associated mutations in the E3 ligase KBTBD4. Here, the authors use cryo-EM to demonstrate how these mutations and UM171 similarly alter KBTBD4 to recruit HDAC1/2, illustrating a natural example of a molecular glue.

Endocannabinoids affect neuronal differentiation, including directional axonal growth during brain development. Here the authors show that endocannabinoids can regulate Slit/Robo interactions during the establishment of forebrain axonal tracts by studying both mouse and human fetal brains.

Gene transfer agents (GTAs) are phage-like particles that mediate lateral gene exchange. Here, the authors provide the structure of the GTA of Rhodobacter capsulatus (RcGTA), which resembles a tailed phage, and describe the conformational changes required for DNA ejection.

Long-chain acyl-Coenzyme-A is a metabolic intermediate with important signaling functions. Here the authors show that it activates the Ca²⁺ selective ion channels TRPV5 and TRPV6 and elucidate the structural basis of TRPV5 activation using CryoEM.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

The higher acceleration gradients of laser ion accelerators opens the way to more compact laser-driven accelerator facilities than the existing conventional ones. The authors find that the acceleration performance is doubled with the use of temporally shaped laser pulses showing that the shaping parameters, easy to introduce in modern lasers, depend on the target characteristics.

In response to acute thermal challenge, thermosensing glutamatergic neurons of the parabrachial nucleus in mouse brain activate tanycytes, which reduce the excitability of Flt1-expressing dopamine and agouti-related peptide-containing neurons, thus suppressing appetite.

The human genome still contains numerous uncharacterized genes. Here, the authors identify a fast evolving Factor associated with Metabolism and Energy (FAME) that is associated with altered body weight, energy expenditure, and metabolism and study its function in knockout mouse models.

The hypothalamus is a brain region rich in functionally segregated neurons. Here Romanov and colleagues use single-cell RNA sequencing to distinguish 62 neuronal subtypes and define their neuropeptide and neurotransmitter makeup. They then show that onecut-3-containing dopamine neurons populate the periventricular area and are wired into the circadian circuitry.

Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.

Pseudomonas putida is becoming a host of choice for the valorization of lignocellulosic substrates. Here, the authors provide insight into the adaptation of this bacterium to the non-native substrate D-xylose, enabled by metabolic engineering and adaptive laboratory evolution.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

The safety and efficacy of ribonucleoproteins for genome editing can be enhanced by formulations of lipid nanoparticles optimized for enhanced stability, delivery efficiency and editing potency of the protein complexes.

Epoxide ring opening reactions are important in both biological processes and synthetic applications. Here, the authors show that flavin cofactors can catalyze reductive and oxidative epoxide ring opening reactions and propose the underlying mechanisms.

Tabular Prior-data Fitted Network, a tabular foundation model, provides accurate predictions on small data and outperforms all previous methods on datasets with up to 10,000 samples by a wide margin.

Ronald Duman and colleagues report that synapse number is reduced in subjects with major depressive disorder. This is associated with decreased expression of synapse-related genes and increased expression of the transcriptional repressor, GATA1. Expression of GATA1 in prefrontal cortex neurons decreases the expression of synapse-related genes, reduces dendrite branching and produces depressive behavior in a rat model of depression.

Interdisciplinary collaboration is essential to understanding and addressing complex public health challenges. On the basis of complex systems science, we suggest actions that public health funders, institutions and researchers can take to fully engage in interdisciplinary work.

Cells can tailor their growth to current conditions by sensing nutrients. The protein complex mTORC1 enables cell growth to be coordinated with the level of certain amino acids, and how it senses the amino acid leucine has now become clearer.

Mechanosensitive channel PIEZO2, but not PIEZO1, can be inhibited by the protein TMEM120A (TACAN), but the mechanism was unclear. Here, the authors show that TMEM120A increases the levels of phosphatidic acid, which is shown to be a selective inhibitor of PIEZO2.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

In mitosis, genome integrity is maintained by DNA polymerase theta-dependent repair of DNA double-strand breaks, which is regulated by Polo-like kinase 1 activity.

As the number of atoms involved in a reaction increases, so do the experimental and theoretical challenges faced when studying their dynamics. Now, using ion-imaging experiments and quasi-classical trajectory simulations, the dynamics of the polyatomic reaction F^– + CH₃CH₂Cl have been studied and the competition between bimolecular nucleophilic substitution and base-induced elimination has been disentangled.