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Experiments at the Joint European Torus tokamak show improved thermal ion confinement in the presence of highly energetic ions and Alfvénic instabilities in the plasma.

A repeated on–off high-temperature shockwave is shown to be a generalizable way of efficiently synthesizing and stabilizing single atoms at high temperatures.

Direct neuronal conversion of skin fibroblasts from individuals with Huntington’s disease (HD) generates a population of medium spiny neurons that recapitulate hallmarks of HD, including aggregation of mutant huntingtin protein, DNA damage and spontaneous cell death.

The role of MYC in transcriptional reprogramming in prostate cancer remains poorly characterized. Here, MYC overexpression antagonizes the canonical AR transcriptional program leading to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.

The atomic-scale frictional processes between two metallic single-crystal asperities are visualized by combining in situ high-resolution TEM and AFM, elucidating diffusion-mediated low friction.

Confining plasma and managing disruptions in tokamak devices is a challenge. Here the authors demonstrate a method predicting and possibly preventing disruptions and macroscopic instabilities in tokamak plasma using data from JET.

This study shows conserved EAG2 potassium channel function in brain tumorigenesis and metastasis, cooperation of different potassium channels for mitotic volume regulation, and EAG2 enrichment at the trailing edge for local volume regulation and cell motility. The authors identified the FDA-approved drug thioridazine as an EAG2 blocker of potential therapeutic value.

A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology.

An on-chip, sub-optical-cycle sampling technique for measuring arbitrary electric fields of few-femtojoule near-infrared optical pulses in ambient conditions is demonstrated, offering an improvement of roughly six orders of magnitude in energy sensitivity compared with those previous works in the near-infrared.

Atomic shuffles are important phenomena accompanying the twinning in hexagonal close-packed crystals, but the direct experimental observation on it is lacking. Here, the authors show the shuffling mechanism of {112 ̅1} twinning in rhenium nanocrystals by in situ transmission electron microscopy.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

As the sample size goes down to the nanoscale, the surface-related mechanism plays an important role in the deformation of nanoscale crystals. Here, the authors report breakdown of the traditional Hall-Petch-like relation in nanoscale Ag attributed to diffusion-involved nucleation behaviors.

Conformation-specific antibodies and longitudinal tracking of individual neurons in situ identifies a toxic monomer species linked to Huntington's disease.

μ-opioid receptor (MOR) was previously shown to be necessary for opiate reward, analgesia and dependence. To better understand the specific anatomical and cell type loci of MOR action in opiate reward and reinforcement learning, the authors use cell-specific rescue expression of MOR in subtypes of neurons in the mouse brain that lack MOR globally and show that MOR in the striatal direct-pathway medium spiny neurons is sufficient to rescue the reward action of opioids without affecting opioid analgesia or withdrawal in MOR knockout mice.

The glycocalyx is a layer of proteoglycans and complex carbohydrates that lines the endothelial cell surface in blood vessels. Schmidt et al. show that in mouse models of sepsis, lung inflammation and injury depend on glycocalyx degradation, which increases neutrophil access to endothelial adhesion molecules. The authors also provide data indicating the potential relevance of this mechanism of lung injury to humans with sepsis.

Joana Carlevaro-Fita, Andrés Lanzós et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice.

Systemic toxicity associated with heterogeneity in the stoichiometries and sites of drug attachment is a major hurdle to developing antibody-drug conjugates (ADCs) for cancer therapy. Junutula et al. engineer cysteine residues in constant domains to produce near-homogenous ADCs that are better tolerated than conventional ADCs, without any loss of antitumor activity.

In situ atomic-scale imaging of deformation in silver nanocrystals reveals that it is possible to achieve deformability and high strength, attributed to a coupling mechanism between crystal slip and surface diffusional creep.

Silicon nanocrystals under shear stress go through an intermediate, diamond-hexagonal phase before becoming amorphous.

Polyglutamine expansion in the androgen receptor, causing X-linked spinal and bulbar muscular atrophy, impairs its function as a transcriptional coactivator regulating an extensive network of proteins involved in protein clearance.

The astronomical event GW170817, detected in gravitational and electromagnetic waves, is used to determine the expansion rate of the Universe, which is consistent with and independent of existing measurements.

Yingbin Liu, Yun Liu, Hui Wang and colleagues perform whole-exome and targeted gene sequencing of gallbladder carcinoma. They identify recurrent somatic alterations in components of the ErbB signaling pathway and show that these alterations are associated with poor clinical outcomes.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Neurons require lifelong maintenance of their transcriptional program, which includes stable expression of cell-type-specific identity genes. A study now shows that PRC2-mediated chromatin repression in adulthood is critical for the maintenance of neuronal identity gene expression and neuronal survival.

Excitatory neurotransmission through NMDA receptors (NMDARs) has a pivotal role in healthy brain function, and its dysfunction has long been implicated in the pathogenesis of neurodegenerative disorders, including Huntington's disease. A new study uncovers a molecular link between mutant huntingtin and aberrant trafficking of an unconventional NDMAR subunit (GluN3A). Targeting this disease mechanism in a Huntington's disease mouse model had multiple therapeutic benefits (pages 1030–1038).

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

Phosphomimetic mutations at huntingtin (Htt) Ser13 and Ser16 within the conserved N-terminal 17-amino-acid domain profoundly suppresses its toxicity in cell and mouse models of Huntington's disease. New research reveals that cell stress acts as a stimulus for double phosphorylation of endogenous Htt, causing its nuclear translocation, and shows that certain chemicals can target such molecular processes in Huntington's disease cell models.

Huntington's disease is a neurodegenerative disease caused by the accumulation of mutant htt protein. Now, two groups led by Dimitri Krainc and Wenzhen Duan report that mutant htt binds and inactivates the deacetylase enzyme SIRT1 and that SIRT1 overexpression is protective in Huntington's disease mouse models.

A report suggests that leucine-rich repeat kinase 2 (LRRK2) can be degraded through chaperone-mediated autophagy (CMA) in the lysosome, and several Parkinson's disease–causing LRRK2 mutants impair CMA-mediated selective degradation of cytosolic substrates.

Hintiryan, Foster et al. present an online mouse cortico-striatal projectome describing projections from the entire cortex to dorsal striatum. Computational neuroanatomic analysis of these projections identified 29 distinct striatal domains. This connectomics approach was applied to characterize circuit-specific cortico-striatal connectopathies in a mouse model of Huntington disease and in monoamine oxidase (MAO) A/B knockout mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease pathogenesis, the authors profiled mRNA in over 600 brain and peripheral tissue samples from Huntington's disease knock-in mice with increasing CAG repeat lengths. Coexpression network analyses reveal 13 striatal and 5 cortical modules that are highly correlated with CAG length and age.

Squeezed states of light have been experimentally demonstrated to improve the performance of the Laser Interferometer Gravitational-wave Observatory (LIGO) in astrophysically relevant frequency regions. This enhanced performance may help to reach the sensitivity required for detecting gravitational waves.

The discovery that a differentiated somatic cell can give rise to a new organism through nuclear transfer cloning touched off a revolution in genetics. A new study outlining how to target genes serially in cows ushers in a new era in large-animal genetics.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

Tokamak plasmas are prone to sudden collapses that terminate the nuclear fusion reactions. This perspective discusses the prediction of these so-called disruptions with artificial intelligence techniques.