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The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

The [1,2]-Wittig rearrangement of allylic ethers is traditionally considered to proceed via formation and recombination of radical pairs. Now it has been shown that an alternative reaction cascade, involving initial enantioselective [2,3]-rearrangement followed by base-promoted anionic fragmentation–recombination that proceeds with high enantiospecificity, allows a catalytic enantioselective [1,2]-Wittig process.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Mucosal influenza vaccines promise enhanced protection but lack defined immune correlates of protection. Here, the authors conduct a phase I trial of an intranasal recombinant influenza A/H5 vaccine with a nanoemulsion adjuvant, demonstrating successful mucosal priming and broad cross-clade immune responses, advancing the development of intranasal influenza vaccines.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

Tree longevity is thought to increase in harsh environments, but global evidence of drivers is lacking. Here, the authors find two different pathways for tree longevity: slow growth in resource limited environments and increasing tree stature and/or slow growth in competitive environments.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Current water-soluble prodrug technologies typically result in a lack of overall improvement in oral bioavailability relative to standard formulation strategies. Here, the authors report water soluble promoiety (Sol-moiety) technology that shows improved oral bioavailability over existing water-soluble prodrug technologies and the ability to switch from intravenous to oral administration.

Genomic coupling theory predicts that speciation progress involves the buildup of genomic associations that manifest in aggregate barriers to gene flow. This study develops approaches to quantify genomic coupling and applies them to a rattlesnake hybrid zone.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

A study demonstrates full energy–momentum matching, and enhanced interaction, between free electrons and photons through a continuum of flatband resonances, realized in a silicon-on-insulator photonic crystal slab.

Gold has a vital role in human society and the global economy, but its production currently causes high levels of environmental pollution. This work reports an approach that can effectively produce gold from both primary and secondary resources without the use of toxic substances such as mercury or cyanide.

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).

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.

Oat is an important food crop, but the genetic diversity within the gene pool remains unclear. Here, the authors report the analyses of worldwide diversity and population structure of hexaploid oat, and identify signatures of structural rearrangements within the germplasm collection.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Coordination of benzene by a tungsten complex can minimize the formation of oligomeric aromatic products in Friedel-Crafts Arylation. Here the authors show that coordinating benzene to tungsten through two carbons (dihapto-coordination) enables a rarely observed double protonation of the bound benzene, allowing its subsequent coupling to a second arene without the need of a precious metal or Lewis acid catalyst.

CD11c⁺T-bet⁺ B cells have been linked with different autoimmune diseases, but targeting these cells has been challenging. Here the authors use an adenosine 2A receptor agonist to deplete these B cells and to inhibit or reverse autoimmune symptoms and pathology in mice.

The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.

Phytoplankton-bacteria interactions regulate the health of marine ecosystems; however, how these interactions are established remains unclear. Here, the authors isolate 15 phytoplankton strains and track the dynamics of their microbiome, identifying specialist and generalist bacteria and the genomic traits enabling these distinct partnerships.

Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.

The approval of first line immune checkpoint blockade (ICB) has improved outcomes for patients with metastatic non-small cell lung cancer (mNSCLC), however, whether patients would benefit more from ICB alone or alongside chemotherapy is unclear. Here, the authors develop a machine-learning based approach to help guide individual treatment selection patients with mNSCLC.

Intergenerational preconditions and historical conferment of opportunity play a role in social mobility. This study considers the geography of relative deprivation to show how different family groups across Great Britain experience different intergenerational outcomes.

This work introduces a pedigree-derived benchmark for single-nucleotide variants, indels, structural variants and tandem repeats, offering a variant map to validate sequencing workflows or to support the development and evaluation of new variant callers.

MERS-CoV ORF4b antagonizes host innate immune response, partially via blocking nuclear import adapter IMPα activity and preventing nuclear translocation of NF-κB. Here, Munasinghe and Edwards et al. biochemically and structurally define the interaction between ORF4b and IMPα-family members and find a non-canonical interaction between ORF4b NLS and IMPα2 and IMPα3.

Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours. Here the authors report that BCA and BCAC patients possess distinct genomic profiles despite histopathological similarities, and identify a recurrent FBXW11 missense mutation (p.F517S) which leads to accumulation of β-catenin in BCA and higher expression of Wnt/β-catenin targets.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts.

Sequencing analysis of tamoxifen-associated uterine cancers and further in vivo analyses suggest that the drug tamoxifen can activate the PI3K pathway in the absence of oncogenic mutations.

This study shows that aboveground plant diversity is only weakly related to belowground mycorrhizal fungal diversity, although these relationships can be stronger at regional scales. Therefore, conservation efforts centered only on plant diversity may overlook critical fungal diversity hotspots.

Invariant natural killer T (iNKT) cells recognize abnormal cells, but their T cell receptor is not variable and kill cancerous or infected target cells without MHC I restriction. Here, the authors show that in a clinical trial, donor-unrestricted allogeneic iNKT cells could be safely administered to human COVID-19 patients suffering from acute respiratory distress syndrome and trigger an anti-inflammatory response.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

A clinical trial using continuous glucose monitoring found that a Dietary Approaches to Stop Hypertension (DASH)-style diet tailored for diabetes reduced hyperglycemia and improved glucose control compared to a typical American diet in patients with type 2 diabetes.

Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.