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Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

A new reprogramming strategy used to produce human induced pluripotent stem cells from somatic cells results in epigenetic and functional profiles that are highly similar to those of human embryonic stem cells.

Analyses of data on 21 billion friendships from Facebook in the United States reveal associations between social capital and economic mobility.

Under continued global warming, lakes will increasingly be covered by white ice, in particular towards the end of the ice cover season when fatal winter drownings occur most often and light limits the growth and reproduction of primary producers.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Mapping enhancer regulation across human cell types and tissues illuminates genome function and provides a resource to connect risk variants for common diseases to their molecular and cellular functions.

Femtosecond laser pulses can generate self-organized nonlinear gratings in nanophotonic waveguides, providing both quasi-phase-matching and group-velocity matching for second-harmonic generation, and enabling simultaneous χ² and χ³ nonlinear processes for laser-frequency-comb stabilization.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

In vivo imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher et al. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.

Human activities, including industry and mining, have increased inorganic mercury deposition in terrestrial and aquatic ecosystems. Model simulations indicate that circumpolar rivers deliver large quantities of mercury to the Arctic Ocean during summer.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

The dynamics of information within complex networks can be captured by a set of operators where the effect of detachment of a node defines the node-networks entanglement, which can be used as a multiscale centrality measure. Here, the authors show that the nodes with high entanglement centrality, which are critical for information dynamics, are also the ones responsible for keeping the network integrated.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Wang and colleagues report that cancer-cell-derived extracellular vesicles that contain miR-122 reprogram glucose metabolism of premetastatic niche cells to alter nutrient availability and promote metastasis.

IL-23 is needed to protect mucosal surfaces from bacterial pathogens. Murphy and colleagues identify a Notch-2-dependent CD11b⁺ dendritic cell population that produces IL-23 and is required for survival after infection with Citrobacter.

Small RNAs targeted to gene promoters are known regulators of transcription in mammalian cells. Antigene RNAs complementary to non-coding transcripts localized to the 3′ termini of genes are now shown to regulate transcription across long genomic sequences.

Analysis of changes in functional groups of species and potential drivers of environmental change for protected areas across the world’s major tropical regions reveals large variation between reserves that have been effective and those experiencing an erosion of biodiversity, and shows that environmental changes immediately outside reserves are nearly as important as those inside in determining their ecological fate.

Long-term resveratrol supplementation procures health benefits at middle-age in a non-human primate but does not mimic the positive effects of calorie restriction on lifespan and might even impair brain integrity at older ages.

In this Perspective, the authors discuss the current status of ecological forecasting research, its role in helping to address the climate and biodiversity crises facing society and potential future directions, with a central focus on how to scale up ecological forecasting capabilities.