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Deconvolution methods infer levels of immune infiltration from bulk expression of tumour samples. Here, authors assess 6 published and 22 community-contributed methods via a DREAM Challenge using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells.

This study shows that mithramycin suppresses the EWS::FLI1 transcription factor in Ewing sarcoma using a hybrid CUT, Tag & GRO assay, revealing mechanism, need for continuous dosing, and supporting clinical use of next-gen analog AIT-102.

Chronic tinnitus is often treated with cognitive-behavioural therapy, hearing aids, counselling, or sound therapy, but their combined benefit is unclear. Here, the authors show, in a multicentre randomised trial, that combination treatments improve tinnitus scores more than single therapies, though benefits appear compensatory rather than synergistic.

Dorsal raphe 5HT(DR^Sert) neurons regulate arousal from hypercapnia by their projections to the neurons in the external lateral parabrachial nucleus (PBel) that are glutamatergic and also express calcitonin gene related peptide (PBel^CGRP). The DR^Sert input to the PBel modulates the arousal system to rising levels of blood CO₂, and may be mediated by 5HT_2a receptors on the PBel^CGRP neurons.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Cell groups in the hypothalamic suprachiasmatic clock contribute to the genesis of circadian rhythms. The authors identified two populations of vasoactive intestinal polypeptide-expressing neurons in the suprachiasmatic nucleus which regulate locomotor circadian rhythm in mice.

Neutron scattering on a model system of highly concentrated solutions of charged carbon nanotubes reveals a strong solvent ordering up to ∼40 Å around the charged nanoscale surface.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

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.

Using high-resolution multi-omic data from biological wastewater treatment plants, the authors develop a method to forecast microbial community composition and function; the forecasting is accurate for 3 yr into the future.

Following a wide-ranging review of studies, reports and policies about nature’s multiple values, combinations of values-centred approaches are proposed to improve valuation of nature, address barriers to uptake in decision-making, and make transformative changes towards more just and sustainable futures.

Currently many of the time resolved serial femtosecond (SFX) crystallography experiments are done with light driven protein systems, whereas the reaction initiation for non-light triggered enzymes remains a major bottle neck. Here, the authors present an expanded Drop-on-Tape system, where picoliter-sized droplets of a substrate or inhibitor are turbulently mixed with nanoliter sized droplets of microcrystal slurries, and they use it for time-resolved SFX measurements of inhibitor binding to lysozyme and secondly, binding of a β-lactam antibiotic to a bacterial serine β-lactamase.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Bacterial malic enzymes (ME) transform malate to pyruvate. One group, hybrid ME enzymes, are regulated by acetyl-CoA, linking the enzyme activity to the metabolic state of the cell. Structures of a representative hybrid ME MaeB reveal large conformational rearrangements that provide insight into the mechanism of allosteric inhibition by acetyl-CoA.

The UN 2030 Agenda for Sustainable Development recognizes the need to transform governance for the world to develop sustainably. Using a mixed method approach, this study presents 13 principles for transformative ocean governance that can help turn ocean-use practices into more sustainable ones.

A computational workflow centered on probabilistic machine learning is developed to reconstruct the energy dispersion from photoemission band-mapping data. The workflow uncovers previously inaccessible momentum-space structural information at scale.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Spin-state crossovers are phenomena where, under changes in temperature or pressure, the spin-state of an ion changes. In some materials, this spin-state crossover occurs simultaneously with a metal-insulator transition, driven by a valence transition. Control over such valence, spin-state, and metal-insulator transitions has much technological appeal, but, thus far, materials displaying this have been limited to cryogenic temperatures. Here, the authors show that in strained films of (Pr1-yYy)1- xCaxCoO3-δ, these transitions can be promoted to room temperature.

Sleep and wakefulness is stabilized by a population of orexin-expressing neurons. In this study, the authors demonstrate how these neurons drive arousal by silencing sleep-promoting neurons in the ventrolateral preoptic nucleus.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

A new study considering data from 7603 households across 28 sites in 22 low- and middle-income countries show that inequality of household water security follows a Development Kuznets Curve.

To mark the 20th anniversary of Nature Reviews Neuroscience, in this Viewpoint article we asked some of the researchers who have authored pieces published in the journal in recent years for their views on how the field, and their areas within it, have developed over the past two decades.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

The histone H3 CENP-A is known to play a role during meiosis but its role in the testes in the fly is unknown. Here, the authors identify the mitochondrial metabolic protein complex ATP synthase F₁ as interacting with CENP-A, promoting centromere cohesion during meiosis and affecting fly fertility.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

A method using semi-stable edge of chaos in LaCoO₃ enables continuous signal amplification in metallic conductors without separate amplifiers, potentially revolutionizing electronic chip design.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Studies in mice show that telomerase reverse transcriptase (TERT) has a role in enhancing stem cell competition that is independent of its reverse transcriptase activity, and promotes chromatin accessibility and activity of the MYC oncogene.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Todd et al. show a daily rhythm in aggression propensity in male mice and reveal a novel polysynaptic circuit within the hypothalamus by which the central circadian clock (the suprachiasmatic nucleus) influences neurons that regulate attack behavior.

Supramammillary nucleus (SuM) neurons have been studied in the context of REM sleep but their possible role in mediating wakefulness is not known. Here the authors elucidate the distinct functional contributions of three subpopulations in the SuM on electrographical and behavioral arousal in mice using genetically targeted approaches.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Analysis of eight taxonomic groups across 186 islands and 423 mainland regions reveals that those with the greatest gross domestic product per capita, human population density and area have the highest established alien species richness, with the strongest effects on islands.