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Resolvins are endogenous lipids with pro-resolving activity. Here the authors find that rats overexpressing human α-synuclein show defects in dopamine signalling before dopamine cell loss, and that this is associated with low Resolvin D1 levels and neuroinflammation.

The MICrONS mouse visual cortex dataset shows that neurons with similar response properties preferentially connect, a pattern that emerges within and across brain areas and layers, and independently emerges in artificial neural networks where these ‘like-to-like’ connections prove important for task performance.

How the ensemble encoding of social and anxiety-related behaviors interacts with encoding of context in the prefrontal cortex of mice is not fully understood. Here authors examine how prefrontal neurons encode socioemotional behaviors in different contexts and reveal that the prefrontal cortex encodes context-invariant representations of these behaviors in parallel with representations of context.

The efficacy of epidural electrical stimulation (EES) to engage arm muscles and improve movement after spinal cord injury is still unclear. Here, the authors investigated how EES can recruit upper-limb motor neurons by combining computational modelling with experiments in non-human primates.

Long-term synaptic potentiation in engram cells of the basolateral amygdala underlies the formation of context fear memory.

The neural circuits in the hindbrain that link satiety and aversion are shown to be separate, raising the possibility of developing obesity drugs without the common side effects of nausea and vomiting.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

Jung et al. show that shelter experience boosts dopamine release in the nucleus accumbens, generating a goal-___location memory. Reactivating a neuronal ensemble developed from shelter experience enables memory-guided navigation to the goal during escape.

The drug daclatasvir (DCV), which inhibits the hepatitis C virus (HCV) non-structural protein 5A (NS5A), can successfully reduce viral load in patients; here, a combination of DCV and an NS5A analogue is shown to enhance DCV potency on multiple genotypes and overcome resistance in vitro and in a mouse model.

The local mutation rate in Escherichia coli has evolved to reduce the risk of deleterious mutations, leading to a non-random occurrence of mutations and suggesting that DNA protection and repair mechanisms preferentially target more important genes.

Chemical synthesis of secondary metabolites isolated from nature, and derivatives thereof, is still a paradigm of significance to drug development. Here the authors instead use bioinformatics to analyze a biosynthetic gene cluster found in the soil metagenome, and chemical synthesis of its predict product to produce lapcin, a dual topoisomerase I/II inhibitor with promising activity against cancer cell lines.

Laramide flat-slab subduction releases fluids into the overlying crust that mediate water-fluxed melting of precursor arc lower crust, ultimately forming porphyry copper deposits, according to a geochronology and thermobarometry study.

Rabies-virus-based tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has limited its applications. Here Jin et al. present a second-generation system with minimal toxicity, using double-deletion-mutant rabies viruses.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

Californium is difficult to prepare in its divalent state. Now, crystals of a Cf(II) crown–ether complex have been synthesized by reduction of a Cf(III) precursor with an Al/Hg amalgam. They exhibit 5f→6d transitions in the visible region and near-infrared emission that are highly sensitive to changes in the coordination environment.

Type III CRISPR-Cas RNases from the Csm and Csx families are activated by cyclic oligoadenylates (cOA). Here the authors present the cOA bound Sulfolobus islandicus Csx1 structure, which forms a hexamer and reveal an allosteric mechanism for the activation of Csx1 RNase.

Designing efficient Bayesian neural networks remains a challenge. Here, the authors use the cycle variation in the programming of the 2D memtransistors to achieve Gaussian random number generator-based synapses, and combine it with the complementary 2D memtransistors-based tanh function to implement a Bayesian neural network.

A continuum spanning from 300 and 3000 nm is used to synthesize a single-cycle field transient and measure its waveform through electro-optic sampling, speeding up this sensitive technique so that it can access the electric field of visible light.

Cognitive deficits are long-lasting consequences of drug use, yet the convergent mechanism by which classes of drugs with different pharmacological properties cause similar deficits is unclear. Here authors show that phencyclidine and methamphetamine both cause glutamatergic neurons in the medial prefrontal cortex to gain a GABAergic phenotype and decrease expression of their glutamatergic phenotype, and further that suppression of drug-induced gain of GABA prevents memory deficits.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Trace metals have been an important ingredient for life throughout Earth’s history. Here, the authors show that a member of an elusive archaeal lineage (Caldarchaeales or Aigarchaeota) requires tungsten for growth, and provide evidence that tungsten-dependent metabolism played a role in the origin and evolution of this lineage.

Our brains constantly detect discrepancies between predicted and observed events to update our knowledge of the world. Here the authors identify a neural signal driving this cognitive update and an inhibitory circuit involved in computing the prediction mismatch.

Aromatic amines can form covalent DNA adducts, in which the damaged base can cause mutations in the vicinity of the lesion. A mechanism for such semi-targeted mutagenesis is now proposed, based on structural and functional data on Dpo4: the bulky lesion-bypass polymerase interaction leads to a conformation of Dpo4 that stabilizes misaligned intermediates.

Quartz emits a piezoelectric charge during deformation that may promote the formation of gold nuggets within veins in orogenic settings that experience earthquakes, according to a study using quartz deformation experiments and piezoelectric modelling.

The medial prefrontal cortex (mPFC) has been implicated in both social and nonsocial reward-related behaviors, yet it is unclear if the same mPFC neurons represent both types of rewards. Combining a social-sucrose operant assay with calcium imaging and optogenetics, the authors show that largely non-overlapping neurons represent social and sucrose rewards in the mPFC.

Striatal hyperactivity has been linked to compulsive behavior, but cell-type and pathway specific mechanisms are unclear. Here, the authors show excessive grooming in Sapap3-KO mice is associated with indirect pathway hyperactivity and suppression of hyperactivity normalizes grooming.

The aggregation of the neuronal protein α-Synuclein is associated with the onset of Parkinson’s disease. Here the authors report a two-dimensional Fragment Assisted Structure-based technique to find antagonists of α-Synuclein aggregation and show its promise for identifying lead therapeutics for Parkinson’s disease.

ONIX is a data acquisition system for recording freely behaving mice. It can accommodate a variety of recording technologies, while maintaining minimal impact on animal behavior.

Activity in anterior deep cerebellar nuclei reduces food consumption in mice without reducing metabolic rate, potentially identifying a therapeutic target for disorders involving excessive eating.

Transcriptomic analysis following epidural electrical stimulation of the lumbar spinal cord during neurorehabilitation in mice identifies a population of neurons that orchestrates the restoration of walking following paralysis.

The preference of cells in mouse primary visual cortex are thought to be randomly distributed in a salt-and-pepper map, in contrast to the smooth cortical maps observed in higher mammals. Here the authors show that excitatory cells in mouse primary visual cortex are spatially clustered, resembling a degraded version of the organization seen in higher mammals.

Using cryo-electron microscopy, the structural mechanism by which non-coding bridge RNA confers target and donor DNA specificity to IS110 recombinases for programmable DNA recombination is explored.

Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

It is demonstrated that the brain circuitry involved in regulating the motivation for physical activity is not strictly central nervous system autonomous but is shaped by peripheral influences that originate in the intestinal microbial community.

A short segment of α-synuclein called NACore (residues 68–78) is responsible for the formation of amyloid aggregates responsible for cytotoxicity in Parkinson disease; here the nanocrystal structure of this invisible-to-optical-microscopy segment is determined using micro-electron diffraction, offering insight into its function and simultaneously demonstrating the first use of micro-electron diffraction to solve a previously unknown protein structure.

A genome-wide CRISPR screen for suppressors and enhancers of C9ORF72 dipeptide-repeat protein toxicity identifies candidate genes involved in nucleocytoplasmic transport and other pathways including RNA processing and chromatin modification.

The mechanisms underlying adaptive response to the stress elicited by radiotherapy in glioma cells remains unclear. Here, the authors show that therapeutic ionizing radiation induces rapid genome-wide chromatin reorganization to facilitate P-TEFb-mediated nascent transcriptional induction, which could be targeted to sensitize radiotherapy response in glioma.

By tracking the activity of CA1 neurons during associative learning, Biane, Ladow et al. reveal the distinct contribution of neurons along the dorsoventral axis of CA1 in the encoding and updating of task-related representations throughout learning.