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First-in-human combined intrathalamic and intrathecal gene therapy in two patients with Tay-Sachs disease provides early evidence on the safety and feasibility of the approach.

Using 13 functional traits we characterize the Amazonian trees and the communities they form. Amazonian tree communities are distributed along a fast-slow-spectrum. This results in clear differences in traits among these forests, as well as their biomass and biomass productivity.

Diffusion modelling of nickel in mantle melts beneath a volcano reveals the short timescales of magma movement from the base of the crust to the surface in the months to years before an eruption.

Results from the first experimental campaign of the Wendelstein 7-X stellarator demonstrate that its magnetic-field design grants good control of parasitic plasma currents, leading to long energy confinement times.

It has been conjectured that an alternative model of quantum computation—in which one only applies two-qubit singlet-vs-triplet measurements to almost any source of input qubits—is as powerful as the usual gate-based model. Here, the authors prove this conjecture, ending up with a model where computations are independent from the way in which one picks the axes of the Bloch sphere.

Approximately half a trillion reef-building corals live across the Pacific Ocean, based on estimates of the population sizes of more than 300 species.

This work reports a quantitative investigation of the interaction parameter and miscibility of donor and acceptor organic molecules and their relationship with the fill factor and photovoltaic performance of bulk-heterojunction organic solar cells.

Gouldian finches have a head colour polymorphism that is also associated with physiological and behavioural differentiation. Here, the authors map this colour polymorphism to a putative regulatory region for follistatin on the Z chromosome and suggest it is maintained by balancing selection.

The existence of a pan-tropical forest carbon sink remains uncertain due to the lack of data from Asia. Here, using direct on-the-ground observations, the authors confirm remaining intact forests in Borneo have provided a long-term carbon sink, but carbon net gains are vulnerable to drought and edge effects.

Triggering and sustaining fusion reactions — with the goal of overall energy production — in a tokamak plasma requires efficient heating. Radio-frequency heating of a three-ion plasma is now experimentally shown to be a potentially viable technique.

Prion protein has been suggested to bind toxic amyloid-ß oligomers. Nicollet al.demonstrate that binding to prion protein and prion protein-dependent synaptotoxicity correlate with the presence of a tubular form of amyloid-ß with a defined triple helical structure.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease with a substantial burden worldwide. In this Consensus Statement, a global multidisciplinary group of experts develop consensus statements and recommendations addressing a broad range of topics on NAFLD to raise awareness and spur action.

In a phase 1 trial in a single patient with hereditary spastic paraplegia type 50, a personalized AAV9-based gene therapy was developed within 3 years from diagnosis and was well tolerated, showing preliminary evidence of disease stabilization.

Arabidopsis thaliana has been engineered to contain two bacterial enzymes to help it remove arsenic from contaminated soils.

Despite expectations that global anthropogenic pressures on species with communities may be size biased, this relationship has not been tested on a large scale. Here the authors use existing databases to show that larger species have not experienced more declines in abundance within their respective communities than small species.

The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing.

Summed probability distributions of radiocarbon dates can be used to estimate past demography, but methods to test for associations with environmental change are lacking. Here, DiNapoli et al. propose an approach using Approximate Bayesian Computation and illustrate it in a case study of Rapa Nui.

A machine learning approach is presented to identify dominant patterns in disease progression in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The nonlinearity of ALS progression has important clinical implications.

How mechanosensitive ion channels, such as MscL, are activated by lipids and physical properties of the membrane remains unclear. Here authors use PELDOR/DEER spectroscopy and identify a single site which generated an allosteric structural response in the absence of membrane tension.

This study reports data from a network of long-term monitoring plots across African tropical forests, which finds that above-ground carbon storage in live trees increased by 0.63 Mg C ha⁻¹ yr⁻¹ between 1968 and 2007. The data is extrapolated to unmeasured forest components, and by scaling to the continent, a total increase in carbon storage in African tropical forest trees of 0.34 Pg C yr⁻¹ is estimated. These results provide evidence that increasing carbon storage in old-growth forests is a pan-tropical phenomenon.

Vascular abnormalities, particularly those associated with rupture of intracranial aneurysms (IAs) or arterial dissections are among the most serious complications of autosomal dominant polycystic kidney disease (ADPKD). In this article, the authors discuss the pathophysiological mechanisms that might be involved in the development of vascular complications in patients with ADPKD and review strategies for screening, diagnosis and treatment of IAs in this population.

Acute heat stress from the extended marine heatwave of 2016 is a potent driver of the transformation of coral assemblages, which affects even the most remote and well-protected reefs of the Great Barrier Reef.

The classical pentraxins, serum amyloid P component (SAP) and C-reactive protein (CRP), are major acute phase reactants in mouse and man. It is shown that pentraxins recognize various FcγRs and SAP opsonization activates FcγR-mediated phagocytosis and cytokine secretion. The receptor binding sites for SAP and IgG overlap, resulting in competition of IgG binding to FcγR as well as inhibition of immune complex-mediated phagocytosis by soluble pentraxins.

Phylogenetic diversity is decoupled from taxon diversity for the Cape Floristic Region of South Africa, a biodiversity hotspot. It turns out that the more species-rich western part of the Cape has lower evolutionary potential than the more neglected eastern part, with important consequences for conservation planning.

The structure of the yeast nuclear pore complex, determined at sub-nanometre precision using an integrative approach that combines a wide range of data, reveals details of its architecture, transport mechanism and evolutionary origins.

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.

Robert de Moya et al. use comparative genomics of avian lice to reconstruct the phylogeny of these parasites. They show that feather lice diversified on the common ancestor of waterfowl and landfowl, and then radiated onto other avian lineages through host-switching.

The timing of cell fate choices is usually unknown, because we have to rely on indirect evidence of their molecular basis. Here, the authors introduce a method to infer decision times from marker onset in cell genealogies, and find evidence refuting the paradigmatic PU.1/GATA1 cell fate switch.

Sparse labelling and whole-brain imaging are used to reconstruct and classify brain-wide complete morphologies of 1,741 individual neurons in the mouse brain, revealing a dependence on both brain region and transcriptomic profile.

Previously documented record values of the fusion triple product in the stellarator Wendelstein 7-X are shown to be evidence for reduced neoclassical energy transport in this optimized device.

New approach methodologies (NAMs) offer the promise of greater predictivity of potential safety risks of drug candidates, especially for newer types of therapeutics for which animal models alone have limited or no applicability for safety testing. This article identifies four categories of drug candidate for which NAMs are applicable and discusses progress in their use based on case studies from recent projects, as well as initiatives to promote the advancement and use of NAMs for more human-relevant safety assessment.

Fine-tuning of TLR7 signaling modulates innate inflammatory responses. Means and colleagues identify the receptor TREML4 as an essential positive regulator of TLR7 signaling during antiviral responses and autoimmunity.

Path integration abilities, important for spatial navigation, vary widely across individuals and deteriorate in old age. This work shows that path integration errors in general, as well as age-related path integration deficits, are mainly caused by accumulating noise in people’s velocity estimation.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Leena Peltonen and colleagues report a genome-wide association study of cholesterol and triglyceride levels in 16 population-based cohorts across Europe. Six new loci were identified, and overall a genetic risk score improves the screening of high risk groups for dyslipidemia.

Elevated rates of reverse weathering within silica-rich oceans led to enhanced carbon retention within the ocean–atmosphere system, promoting a stable, equable ice-free climate throughout Earth’s early to middle ages.