Research articles

Mice lacking the mechanically activated ion channel Piezo2 in both sensory neurons and Merkel cells are almost totally incapable of light-touch sensation while other somatosensory functions, such as mechanical nociception, remain intact, implying that other mechanically activated ion channels must now be identified to account for painful touch sensation.

A study of freely moving bats provides new insights into how the brain encodes a three-dimensional neural compass; neurons were identified encoding the three Euler rotation angles of the head (azimuth, pitch, and roll) and recordings from these head-direction cells revealed a toroidal model of spatial orientation mapped out by cells tuned to two circular variables (azimuth × pitch).

This study uses single-cell expression profiling of pluripotent stem cells after various perturbations, and uncovers a high degree of variability that can be inherited through cell divisions—modulating microRNA or external signalling pathways induces a ground state with reduced gene expression heterogeneity and a distinct chromatin profile.

A new role for the endosomal sorting complex required for transport (ESCRT) is identified in fly larvae, where it is shown to be essential for the secretion and long-range signalling of the embryonic development morphogen Hedgehog.

A high-velocity outflow of molecular gas from a starburst galaxy has been observed to extend about ten kiloparsecs; its velocity is consistent with the momentum flux from stellar radiation pressure, showing that bursts of star formation can eject large amounts of cold gas from the central regions of galaxies, curtailing star formation.

Angelman syndrome is a neurodevelopmental disorder caused by disrupted function of the maternal copy of the imprinted UBE3A gene; here, targeting a long non-coding RNA that is responsible for silencing the paternal copy of UBE3A with antisense oligonucleotides is shown to partially restore UBE3A expression in the central nervous system and correct some cognitive deficits in a mouse model of the disease.

Using electron cryomicroscopy, the closed-state structure of rabbit RyR1 is determined at 4.8 Å resolution; analysis confirms that the RyR1 architecture consists of a six-transmembrane ion channel with a cytosolic α-solenoid scaffold, and suggests a mechanism for Ca²⁺-induced channel opening.

The X-ray crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate is described.

Four different XNAs — polymers with backbone chemistries not found in nature, namely, arabino nucleic acids, 2′-fluoroarabino nucleic acids, hexitol nucleic acids and cyclohexene nucleic acids — are found to be able to support the evolution of synthetic enzymes (XNAzymes) that catalyse several chemical reactions.

Electron cryomicroscopy reveals the three-dimensional structure of F-actin at a resolution of 3.7 Å in complex with tropomyosin at a resolution of 6.5 Å; the stabilizing interactions and the effects of disease-causing mutants are also investigated.

Using electron cryomicroscopy, the structure of the rabbit RyR1 calcium channel is determined at 6.1 Å resolution in the closed state and 8.5 Å in the open state, revealing how calcium binding to the EF-hand of RyR1 regulates channel opening and facilitates calcium-induced calcium release.

Analysis of data obtained by probe spacecraft shows that ultrarelativistic electrons in the Van Allen radiation belts are prevented from entering a sharply defined region around the Earth, possibly owing to a combination of slow natural inward diffusion and pitch angle scattering.

A simulation of the evolution of El Niño Southern Oscillation in the past 21,000 years in a state-of-the-art climate model shows the complex response mechanisms of El Niño to external climate forcings and poses further challenges to our understanding and projection of El Niño in the future.

A combination of genome-wide exome and transcriptome analysis, mass spectrometry and computational structural modelling are used here to identify immunogenic neo-antigens in two mouse tumour cancer cell lines; mice vaccinated with predicted immunogenic peptides yielded therapeutically useful cytotoxic T-lymphocyte responses.

Deep-genome and single-cell sequencing analyses of patient-derived breast cancer xenografts reveal extensive, dynamic and reproducible changes in intra-tumoral mutational clonal composition on engraftment and serial propagation.

Malaria-carrying mosquitoes nearly disappear in the dry season, yet they reappear suddenly following the first rains; using surveys of mosquito densities, the authors characterize the population dynamics of the three main vector species and use these to infer persistence by long-distance migration in two species and aestivation in the third.

The radiation-damage-free structure of the photosystem II membrane protein complex, which oxidizes water into dioxygen in an oxygen evolving complex, has been determined by an X-ray free electron laser at a resolution of 1.95 Å; one of the substrate oxygen atoms in this reaction is now identified.

A multilayer photonic structure is described that strongly reflects incident sunlight while emitting heat selectively through an atmospheric transparency window to outer space; this leads to passive cooling under direct sunlight of 5 degrees Celsius below ambient air temperature, which has potential applications in air-conditioning and energy efficiency.

The dynamics of T-cell responses are investigated in tumour tissue from patients with advanced melanoma who were treated with a PD-1-blocking monoclonal antibody, revealing that clinical efficacy of the treatment correlates with increased frequencies of pre-existing CD8⁺ T cells and PD-1 and PD-L1 expression.

Clinical and correlative biomarker results from a phase 1 clinical trial in patients with different solid tumours are presented; the findings indicate that PD-L1 expression on tumour-infiltrating immune cells is associated with clinical response to MPDL3280A (anti-PD-L1).