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Here, the authors show that reactivating motor memories during sleep at moments of high (vs. low) neuronal excitability (up vs. down phases of slow oscillations) enhances their consolidation. Up-reactivation strengthens sleep markers of plasticity and the neural responses supporting memory consolidation.

In an analysis of long-term safety events in 783 patients treated with T cell therapy in 38 trials, 2.3% of patients developed second primary malignancies, and vector integration analyses revealed no pathological insertions.

Heterostructures formed by the magnetic topological insulator Cr-doped (Bi,Sb)₂Te and the antiferromagnet CrSb are shown to exhibit emergent interfacial magnetic phenomena that can be tuned with the heterostructure geometry.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Using data from the Tara Pacific expedition, this study reports the biogeography and the diversity of microbiomes collected from corals, fish and plankton in 99 reefs across the Pacific Ocean. The large richness of Pacific Ocean reef microorganisms, when extrapolated to all fish and corals of the Pacific, represents the current estimated total prokaryotic diversity for the entire Earth.

Analysis of the genomes of 50 species of Lemuriformes shows high levels of genomic diversity, likely due to allele sharing, as well as population declines and inbreeding patterns resulting from ecological factors and human impacts in Madagascar.

Energy homeostasis requires brain sensing of peripheral metabolic signals. Here, the authors show that energy-state-dependent aggrecan deposits by hypothalamic neurons at a key interface gate brain entry of blood-borne signals and thus food intake.

The Southern Annular Mode (SAM) has shifted towards its positive phase owing to ozone depletion and increasing greenhouse gas concentrations. This Review discusses the dynamics, trends and projections of the SAM and how these will affect southern high-latitude climate, including Southern Ocean circulation, carbon cycling and the Antarctic cryosphere.

The role of TRPV1 in the CNS is not fully understood. Here the authors show that TRPV1 is expressed specifically in somatostatin-positive OLM interneurons of the hippocampus, where it promotes excitatory innervation of these cells.

Zikherman and colleagues uncover a new mechanism by which B cells recognize virus-like antigen display as a stand-alone danger signal (independent of nucleic acid cargo) that does not rely exclusively on avidity and BCR cross-linking.

The tumour immune microenvironment is known to be suppressive to immune cells, but the causal functional and metabolic cues are not fully known. Here authors show that tumour cells skew the metabolism of multiple types of intra-tumour dendritic cells via their own altered carbohydrate pattern, which could be mitigated by the inhibition of lactate transport.

Approaches for temporal analysis and quantitative characterisation of single cell morphology and dynamics remain in high demand. Here authors present CellPhe, a pattern recognition toolkit for the unbiased characterisation of cellular phenotypes within time-lapse videos.

Isolated human and mouse enteric nervous system stem cells (ENSCs) are capable of integrating and promoting innervation of the mouse colon. Here the authors show that transplantation of mouse ENSCs into a mouse model of human enteric neuropathy restores colon motility.

Aortic aneurysm and dissection, the major problem linked to Marfan syndrome (MFS), lacks effective pharmacological treatment. Here, the authors show that the NO pathway is overactivated in MFS and that inhibition of guanylate cyclase and cGMP-dependent protein kinase reverts MFS aortopathy in mice.

Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. In this work, authors develop a bacteriocin secretion platform, and test, in a proof-of-concept study, antimicrobial efficacy against Enterococcus faecalis and Enterococcus faecium.

Microtubule-destabilizing drugs and oncolytic viruses are two unrelated approaches to battle cancer. Here the authors show that microtubule-destabilizing drugs potentiate the efficiency of oncolytic rhabdoviruses by altering the cytokine production and response of the tumour cells.

Genome-wide association studies of individuals from an isolated population (data from the Finnish biobank study FinnGen) and consequent meta-analyses facilitate the identification of previously unknown coding variant associations for both rare and common diseases.

Some bacterial toxin-antitoxin systems consist of a labile antitoxin that inhibits a toxin, and a chaperone that stabilizes the antitoxin. Here, Bordes et al. identify a sequence within the antitoxin to which the chaperone binds and which can be transferred to other proteins to make them chaperone-dependent.

Combining in situ nanoprobe techniques paves the way for gaining insights into structure-selectivity relations for electrocatalysts. Herein, the dynamic evolution of lattice strain in individual nanoparticles is directly visualized with nanoscale resolution in Cu-Ag tandem catalysts during the electrocatalytic conversion of CO2 into value-added chemicals.

Simultaneous mapping of activity across the cortex and dorsal striatum in mice shows that activity in each part of the striatum precisely mirrors that in topographically associated cortical regions, consistently across behavioural contexts.

Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.

Despite a wealth of knowledge on astrocytes, their contribution to cerebrovascular maturation is less known. Here, the authors identify a molecule produced by astrocytes which controls astrocyte morphology and their placement on brain blood vessels.

The current use of immune checkpoint inhibitors without chemotherapy on patients with metastatic breast cancer (MBC) has not proven useful. Here this group reports a phase 2 NIMBUS trial evaluating the efficacy/safety of nivolumab + low dose ipilimumab in 30 patients with hypermutated HER2-negative MBC.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Biotech firms are vying to harness the potential of RNA interference. But will its impact be in finding new disease targets, or in RNA-based drugs? Julie Clayton investigates.

Although neutral and anionic low-valent aluminium complexes are widespread, their cationic counterparts have remained rare. Now, a salt of [Al(AlCp*)₃]⁺ featuring a formal low-valent Al⁺ cation has been isolated that dimerizes in concentrated solutions and the solid state, and also forms Al₄ clusters on coordinating with Lewis bases.

Quantitative multimodal 3D reconstruction of human pancreatic tissue at single-cell resolution reveals a high burden of multifocal, genetically heterogeneous pancreatic intraepithelial neoplasias in the normal adult pancreas.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

During mitosis, kinesin-5 motors are thought to crosslink microtubules in a muscle-like sliding filament mechanism. By combining electron microscopy with other structural tools, the authors reveal how four kinesin-5 polypeptides are organized into bipolar minifilaments.

Using a battery of statistical tools, Alagöz et al. examine the genetic overlap between dyslexia and rhythm impairment and shed light on how the genome influences the neural bases of human language and musicality.

Patient drug regime compliance is a major issue; sustained release implants could address this. Here, the authors report on a phase inverted in situ forming implant of PLGA for the sustained release of antiretroviral drugs and optimize and demonstrate the release of 6 different drugs over a period of up to a year.

Sensitisation of dorsal root ganglia neurons contributes to neuropathic pain. Here the authors demonstrate the cytokine FL contributes to sensitisation of DRGs via its receptor FLT3 expressed on neurons, and identify a novel FLT3 inhibitor that attenuates neuropathic pain in mice.

Insulin therapies for patients with diabetes have challenges, including diminished hepatic preference of insulin action compared with endogenous insulin. Here the authors characterize insulin dimers that function as insulin receptor partial agonists, and exhibit hepatic and adipose tissue preference of insulin action and metabolic benefits in preclinical models.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

In this non-comparative trial, patients with BRAF^V600-mutant resectable melanoma received either pembrolizumab alone, a sequential combination of pembrolizumab, dabrafenib and trametinib, or a concurrent combination thereof, showing encouraging clinical response rates in the concurrent therapy arm and awaiting longer follow-up.

Maternal immune activation during pregnancy can negatively impact the developing fetus. Here, applying multi-omics (RNA-seq, phosphoproteomics and lipidomics) and imaging, the authors show that while maternal immune activation induces strong innate response in maternal organs it does not extend through the placenta but leads to fetal metabolic changes.

During epileptic seizures, neural activity across the brain switches into a hyperactive and hypersynchronized state. Here, the authors report on the role of glia-glia and glia-neuron interactions in mediating the changes that result in the ictal state in a zebrafish model of epilepsy.

Many behaviours depend on predictions about the environment. Here the authors find neural populations in primary visual cortex to straighten the temporal trajectories of natural video clips, facilitating the extrapolation of past observations.

Treatment with anti-PDL1 and anti-CTLA4 in combination with mFOLFOX6 chemotherapy for patients with treatment-naive microsatellite stable metastatic colorectal cancer is safe, shows encouraging progression-free survival and induces a tumor-specific immune response.

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 small ubiquitin-like modifier SUMO can be conjugated to hundreds of protein species to affect their stability or activity. Here the authors use a quantitative proteomics approach to identify sumoylated proteins modified by the STUbL and Ufd1 pathways in fission yeast.

A large-scale metagenomic analysis of plant and mammal environmental DNA reveals complex ecological changes across the circumpolar region over the past 50,000 years, as biota responded to changing climates, culminating in the postglacial extinction of large mammals and emergence of modern ecosystems.