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Non-rapid eye movement (NREM) sleep is associated with increased cerebrospinal fluid (CSF) flow in mammals, but this link has not been studied in birds. Here, the authors show that in pigeons, REM sleep is associated with activation of visual brain regions and a drop in CSF flow, suggesting that REM sleep functions occur at the expense of waste clearance during NREM sleep.

Export of proteins by type three secretion systems occurs through an export gate that is localized in the periplasm. Here, the authors present the cryo-EM structure of the Vibrio mimicus export gate complex with FlhB, which plays a major role in switching of the specificity of secretion substrates and propose a mechanism for export gate opening.

Naked mole rat (NMR) is an exceptionally long-lived rodent species that on the phenotypic level seems to evade aging. Here the authors show that NMRs age epigenetically, while epigenetic clocks detect that NMR queens age more slowly than nonbreeding females.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

Multifocal imaging suffers from a number of limitations. Here the authors report an open-source 3D reconstruction algorithm to enable label-free tracking of spherical and filamentous structures which they use to characterise fluid flow and flagellar beating of human and sea urchin sperm.

Experiment based on knocking out an alpha particle from a high-energy helium isotope shows a resonance-like structure that is consistent with a quasi-bound tetraneutron state existing for a very short time.

Inventory data from 90 lowland Amazonian forest plots and a phylogeny of 526 angiosperm genera were used to show that taxonomic and phylogenetic diversity are both predictive of wood productivity but not of biomass variation.

The cryo-EM structure of the bovine rod CNG channel, isolated from retina, sheds light onto the structural basis for the subunit stoichiometry and reveals an additional gate within the ion conduction pathway contributed by the CNGB1 subunit.

A tectothalamic pathway for social affiliation in developing zebrafish dissociates neuronal control of attraction from repulsion during affiliation, revealing a circuit underpinning of collective behaviour

The nature of the microbial reactions occurring during cap rock formation is poorly understood. Here the authors find that sulfur and carbon isotope signatures indicate sulfate-dependent anaerobic oxidation of methane (AOM) as a primary driver of cap rock carbonate formation.

Structural characterization sheds mechanistic insights behind λN-dependent processive antitermination.

Most of the archaeological record of the Middle to Later Stone Age transition comes from southern Africa. Here, Shipton et al. describe the new site Panga ya Saidi on the coast of Kenya that covers the last 78,000 years and shows gradual cultural and technological change in the Late Pleistocene.

The lungs are the main site of entry for most viral pathogens. In this Focus Review, Chiu and Openshaw discuss adaptive immune responses to lung-tropic viruses and implications for vaccine development.

Observation of ²⁸O and ²⁷O through their decay into ²⁴O and four and three neutrons, respectively, is reported, with the ²⁸O nucleus being of particular interest owing to proton and neutron magic numbers and its extremely asymmetric neutron-to-proton ratio.

In this Perspective the authors provide a comparison of recent neurophysiological findings on the pathophysiology of three major movement disorders: Huntington's disease, l-DOPA-induced dyskinesia and dystonia. Both clinical and preclinical studies show that these hyperkinetic disorders share mechanisms underlying synaptic scaling and synaptic plasticity alterations in the basal ganglia–thalamo-cortical network.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Bacteria sequester key metabolic steps into polyhedral protein compartments. A newly discovered nanocompartment reveals what it takes for its cargo protein to become encapsulated within a protein shell.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

The authors generated a Synthetic Morphogenic Membrane System by encapsulating a dynamic microtubule aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized liposomes. This reconstitution of artificial proto-cells reveals how non-equilibrium phenomena affect cellular information processing in morphogenesis.

Pamela Sklar and colleagues report a genome-wide association study of bipolar disorder and identify variants in the genes encoding ankyrin-3 and the alpha-1C subunit of the L-type voltage-gated calcium channel as increasing risk.

Effective therapeutic platforms should combine serum stability, selective targeting, and controlled drug release. Here, the authors self-assemble an aptamer-based nanoscaffold that contains separate cell-targeting and photo-regulated drug-carrying domains, realizing multiple therapeutic functionalities in a single construct.

Toll-like receptors on lung epithelia recognize allergens and help provoke asthma. The findings put new emphasis on innate immunity as a driver of allergic responses (pages 410–416).

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

The escape of mature malaria parasites from the confines of their host red blood cells is an essential yet poorly understood process. Recent studies now highlight a key role for parasite proteases that trigger the degradation of parasite and host membranes, leading to the egress of infectious parasite forms.

How do individuals attribute dispositional properties, or traits, to others? A study suggests that associative learning processes underlie aspects of trait learning at both neural and behavioral levels.

Central nervous system (CNS) control of systemic nutrient homeostasis is a crucial but poorly understood metabolic regulatory axis. A new study (484–492) shows that rat insulin promoter (RIP)-expressing neurons in the hypothalamus regulate peripheral metabolic responses to both normal and high-fat diets through anti-inflammatory effects mediated by vagal innervation of the spleen.

Little is known about how pathogenic T cells gain access to the uninflamed brain in multiple sclerosis and experimental autoimmune encephalomyelitis. A new study reports that interleukin 17–producing T helper cells enter the uninflamed central nervous system through the choroid plexus by a CCR6-CCL20–dependent mechanism.

Lymphocyte development must be tightly regulated in utero to prevent rejection. New work shows that the zinc finger protein Zfp608 negatively regulates the expression of recombination-activating genes 1 and 2 and may suppress fetal T cell development.

Cyclin-dependent kinase 12 (Cdk12) phosphorylates the C-terminal domain (CTD) of RNA polymerase II to regulate transcription. Here, the authors solve the crystal structure of the Cdk12 kinase domain and show that Cdk12 has its highest activity on a CTD substrate that carries a serine 7 phosphorylation.

Patients’ selection is particularly important in cancer treatment. Here the authors present a proof-of-principle methodology that could be potentially important in assisting therapeutic decisions in the treatment of breast cancer patients.

The DNA nanoengine constitutes a chemical energy-driven unidirectional rotor that directionally walks along a predefined multistep track.

After years of waiting, the road map for the path of the mRNA on the ribosome with its associated tRNAs has been completed. In contrast to the amino-acid-coding nucleotides of the body of the mRNA, the Shine-Delgarno region appears to take an unexpected turn on the surface of the 30S subunit in the transition from the initiation complex to the postinitiation complex.

Activation-induced cytidine deaminase (AID), which mediates antibody diversification, is now implicated as an inducer of p53 mutagenesis in cancer cells (pages 470–476).

Toll-like receptor signaling induces the production of proinflammatory cytokines and type I interferons. Inhibition of the kinase IRAK1 by the phosphatase SHP-1 provides reciprocal regulation of these pathways by dampening the former while enhancing the latter.

Natural killer (NK) cells, originally so named because they have the capacity to kill other cells without activation, can be licensed and educated to regulate tissue homeostasis. This notion has recently been shown in reproduction—in both normal physiology by Hanna et al. and severe pathophysiology (preeclampsia) by Hiby et al.

Toll-like receptor (TLR) signaling must be tightly regulated to avoid uncontrolled inflammation. A fifth Toll–interleukin 1 receptor adaptor domain, SARM, has been identified as an inhibitor of TLR3 and TLR4 signaling.

Infections with fimbriated bacteria may trigger autoimmunity and cause a form of severe vasculitis that affects capillaries in the kidney and that can destroy the organ (pages 1088–1096).

Damaged mitochondria are targeted for mitophagy by the Pink–Parkin ubiquitin pathway. The mitochondrial ATPase Atad3a prevents aberrant activation of Pink and protects hematopoietic stem cells.