| | Human embryology: Implantation barrier overcome
The early stages of human development are normally hidden within the womb, but improved techniques for culturing embryos from the blastocyst stage promise to make these steps easier to investigate. | Celestial mechanics: Fresh solutions to the four-body problem
Describing the motion of three or more bodies under the influence of gravity is one of the toughest problems in astronomy. The report of solutions to a large subclass of the four-body problem is truly remarkable. | Depression: Ketamine steps out of the darkness
The way in which ketamine exerts its antidepressant effects has been perplexing. Evidence that a metabolite of the drug is responsible, and acts on a different target from ketamine, might be the key to an answer. | Neurobiology: Wired for sex
Analysis of a sensory neural circuit in the roundworm Caenorhabditis elegans reveals that its wiring is sex-specific, and arises through the elimination of connections that are originally formed in both sexes. | Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Whole-genome sequencing of tumours from 560 breast cancer cases provides a comprehensive genome-wide view of recurrent somatic mutations and mutation frequencies across both protein coding and non-coding regions; several mutational signatures in these cancer genomes are associated with BRCA1 or BRCA2 function and defective homologous-recombination-based DNA repair. | Activation of NMDA receptors and the mechanism of inhibition by ifenprodil
X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology were used to study the conformational changes that take place during the activation and inhibition of a mammalian GluN1b–GluN2B N-methyl-D-aspartate receptor. | Sex-specific pruning of neuronal synapses in Caenorhabditis elegans
How sex-specific neuronal circuits are generated during development is poorly understood; here, sensory neurons are identified in the round worm Caenorhabditis elegans, which initially connect in both male- and hermaphrodite-specific patterns, but a specific subset of these connections is pruned by each sex upon sexual maturation to produce sex-specific connectivity patterns and dimorphic behaviours. | The genetic history of Ice Age Europe
Analysis of ancient genomic data of 51 humans from Eurasia dating from 45,000 to 7,000 years ago provides insight into the population history of pre-Neolithic Europe and support for recurring migration and population turnover in Europe during this period. | NMDAR inhibition-independent antidepressant actions of ketamine metabolites
The metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and the (2R,6R)-HNK enantiomer lacks ketamine-related side effects but exerts rapid and sustained antidepressant actions in mice; these antidepressant effects are independent of NMDAR inhibition but require AMPAR activity. | Continuous probing of cold complex molecules with infrared frequency comb spectroscopy
Combining cavity-enhanced direct frequency comb spectroscopy with buffer gas cooling enables rapid collection of well-resolved infrared spectra for molecules such as nitromethane, naphthalene and adamantane, confirming the value of the combined approach for studying much larger and more complex molecules than have been probed so far. | No Sun-like dynamo on the active star ζ Andromedae from starspot asymmetry
Infrared interferometry imaging of the old, magnetically active star ζ Andromedae reveals an asymmetric distribution of starspots, unlike the north–south starspot symmetry observed on the Sun, meaning the underlying dynamo mechanisms must be different. | Temperate Earth-sized planets transiting a nearby ultracool dwarf star
Three Earth-sized planets—receiving similar irradiation to Venus and Earth, and ideally suited for atmospheric study—have been found transiting a nearby ultracool dwarf star that has a mass of only eight per cent of that of the Sun. | Self-assembly of coherently dynamic, auxetic, two-dimensional protein crystals
Mutants of the C4-symmetric protein RhuA were designed to self-assemble into two-dimensional crystalline lattices with precise spatial arrangements and patterns; the lattices of one of the variants are auxetic and deform perpendicularly to an applied force in a way that is contrary to what is generally expected in typical materials. | Opponent and bidirectional control of movement velocity in the basal ganglia
Activity in the direct and indirect basal ganglia pathways can bidirectionally control the speed of movements that underlie reward-seeking actions in mice without affecting motivation. | Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation OPEN
A novel approach is used to cultivate a substantial proportion of the human gut microbiota, representing an important step forward in characterizing the role of these bacteria in health and disease. | Metabolic acceleration and the evolution of human brain size and life history
Compared to other apes, humans live longer, reproduce faster and have larger brains; here, total energy expenditure is studied in humans and all species of great ape, and is shown to be significantly higher in humans, demonstrating that the human lineage has experienced an energy-boosting acceleration in metabolic rate. | Architecture of the mitochondrial calcium uniporter
The structure of the core region of the mitochondrial calcium uniporter (MCU) is determined by NMR and electron microscopy, revealing that MCU is a homo-pentamer with a specific transmembrane helix forming a hydrophilic pore across the membrane, and representing one of the largest membrane protein structures characterized by NMR spectroscopy. | Crystal structure of the human sterol transporter ABCG5/ABCG8
The X-ray structure of human ABCG5/ABCG8 heterodimer in a nucleotide-free state, being the first atomic model of an ABC sterol transporter. | Activation of the A2A adenosine G-protein-coupled receptor by conformational selection
The adenosine A2A receptor, a class A G-protein-coupled receptor, exists as an ensemble of two inactive and two active states in equilibrium and is activated by conformational selection rather than induced fit. | Self-organization of the in vitro attached human embryo
An in vitro model to study the early events that direct human embryo development after formation of the blastocyst and implantation in the uterine wall. | Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response
In the context of mitochondrial genome heteroplasmy that causes defective oxidative phosphorylation in C. elegans, the ATFS-1-mediated mitochondrial unfolded protein response maintains the deleterious mitochondrial DNA in an attempt to recover oxidative phosphorylation activity and avoid cellular dysfunction. | | Erratum: Universal resilience patterns in complex networks | | Corrigendum: Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome | | Direct detection of the 229Th nuclear clock transition
Direct detection of the 229Th nuclear clock transition has been achieved, placing direct constraints on transition energy and half-life; these results are a step towards a nuclear clock, nuclear quantum optics and a nuclear laser.
Lars von der Wense, Benedict Seiferle, Mustapha Laatiaoui et al. | Principles underlying sensory map topography in primary visual cortex
Recordings from cat visual cortex show that the cortical maps for stimulus orientation, direction and retinal disparity depend on an organization in which thalamic axons with similar retinotopy and light/dark responses are clustered together in the cortex.
Jens Kremkow, Jianzhong Jin, Yushi Wang et al. | Continuous evolution of Bacillus thuringiensis toxins overcomes insect resistance
Phage-assisted continuous evolution (PACE) rapidly evolves Bacillus thuringiensis toxins through more than 500 generations of mutation, selection, and replication to bind a receptor expressed on the surface of insect-pest midgut cells.
Ahmed H. Badran, Victor M. Guzov, Qing Huai et al. | | Resolved atomic lines reveal outflows in two ultraluminous X-ray sources
Ultraluminous X-ray sources are thought to be powered by accretion onto a compact object; now the discovery of X-ray emission lines and blueshifted absorption lines in the high-resolution spectra of ultraluminous X-ray sources NGC 1313 X-1 and NGC 5408 X-1 shows that in each case the compact object is surrounded by powerful winds with an outflow velocity of about 0.2 times that of light.
Ciro Pinto, Matthew J. Middleton, Andrew C. Fabian | Scalable and sustainable electrochemical allylic C–H oxidation
An electrochemical C–H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity is described; it uses inexpensive and readily available materials and represents a scalable allylic C–H oxidation that could be adopted in large-scale industrial settings without substantial environmental impact.
Evan J. Horn, Brandon R. Rosen, Yong Chen et al. | Polar metals by geometric design
Ab initio calculations are used to identify the structural conditions under which a polar state in metals might be stabilized; this information is used to guide the experimental realization of new room-temperature polar metals.
T. H. Kim, D. Puggioni, Y. Yuan et al. | Machine-learning-assisted materials discovery using failed experiments
Failed chemical reactions are rarely reported, even though they could still provide information about the bounds on the reaction conditions needed for product formation; here data from such reactions are used to train a machine-learning algorithm, which is subsequently able to predict reaction outcomes with greater accuracy than human intuition.
Paul Raccuglia, Katherine C. Elbert, Philip D. F. Adler et al. | Chondritic xenon in the Earth’s mantle
High-precision analysis of magmatic gas from the Eifel volcanic area in Germany suggests that the light xenon isotopes reflect a chondritic primordial component that differs from the precursor of atmospheric xenon, consistent with an asteroidal origin for the volatile elements in the Earth’s mantle.
Antonio Caracausi, Guillaume Avice, Peter G. Burnard et al. | The genetic program for cartilage development has deep homology within Bilateria
Vertebrate and invertebrate cartilage share structural and biochemical properties, and their development is controlled by a highly conserved genetic circuit, suggesting that a deeply homologous mechanism underlies the parallel evolution of cartilage in Bilateria.
Oscar A. Tarazona, Leslie A. Slota, Davys H. Lopez et al. | Topology of ON and OFF inputs in visual cortex enables an invariant columnar architecture
Two-photon imaging of calcium signals in the tree shrew visual cortex shows that light-responsive and dark-responsive inputs have distinct arrangements that allow the cortex to map the orientation, visual location and spatial phase of visual stimuli.
Kuo-Sheng Lee, Xiaoying Huang, David Fitzpatrick | Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression
A CRISPR/Cas9 system is used to dissect the role of allelic risk variants on the expression of the α-synuclein gene SNCA, which has been linked to Parkinson’s disease development.
Frank Soldner, Yonatan Stelzer, Chikdu S. Shivalila et al. | Unique human immune signature of Ebola virus disease in Guinea
Fatal Ebola virus disease is characterized by a high proportion of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, correlating with high virus load; individuals who survive the infection exhibit lower expression of these inhibitory molecules and generate Ebola-specific CD8+ T cells, suggesting that dysregulation of the T cell response is a key component of Ebola virus disease pathophysiology.
Paula Ruibal, Lisa Oestereich, Anja Lüdtke et al. | A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges
A single injection of four anti-HIV-1-neutralizing monoclonal antibodies blocks repeated weekly low-dose virus challenges of simian/human immunodeficiency virus.
Rajeev Gautam, Yoshiaki Nishimura, Amarendra Pegu et al. | EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells
The differentiation of T follicular helper cells requires the G-protein-coupled receptor Ebi2 as well as the interaction with CD25-producing dendritic cells that quench T-cell-derived interleukin-2.
Jianhua Li, Erick Lu, Tangsheng Yi et al. | Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells
Defects in LC3-associated phagocytosis in mice are shown to result in systemic lupus erythematosus-like disease; dying cells are engulfed but not degraded in LAP-deficient mice, resulting in increased serum levels of autoantibodies and inflammatory cytokines, and evidence of kidney disease.
Jennifer Martinez, Larissa D. Cunha, Sunmin Park et al. | Ubiquitination independent of E1 and E2 enzymes by bacterial effectors
An unprecedented mechanism of ubiquitination that is independent of E1 and E2 enzymes, instead relying on activation of ubiquitin by ADP-ribosylation, and which is mediated by members of the SidE effector family encoded by the bacterial pathogen Legionella pneumophila, establishes that ubiquitination can be carried out by a single enzyme.
Jiazhang Qiu, Michael J. Sheedlo, Kaiwen Yu et al. | Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9
A CRISPR/Cas9 genome editing framework has been developed that allows controlled introduction of mono- and bi-allelic sequence changes, and is used to generate induced human pluripotent stem cells with heterozygous and homozygous dominant mutations in amyloid precursor protein and presenilin 1 that have been associated with early onset Alzheimer’s disease.
Dominik Paquet, Dylan Kwart, Antonia Chen et al. | | | | |
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