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Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Oncolytic viruses (OVs) represent a treatment option for patients with cancer. Here the authors propose a tumour-agnostic dual-virus strategy for cancer therapy by generating a vesicular stomatitis virus encoding a truncated version of HER2, combined with a vaccinia virus as a delivery platform for a HER2-targeted T-cell engager.

Piff and Wiwad et al. find that attributing poverty to situational forces is associated with greater concern for inequality, and three experiments reveal that increasing situational attributions for poverty motivates egalitarianism up to 5 months later.

Current understanding of Long COVID is limited, in part, due to lack of evidence from population-representative studies. Here, the authors analyse data from ten UK population-based studies and electronic health records, and find wide variation in the frequency of Long COVID between studies but some consistent risk factors.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Esophageal adenocarcinoma is characterised by frequent amplifications in oncogenes. Here, the authors use short- and long-read sequencing approaches to analyze primary tumor samples and tumour-derived organoids and to investigate the mechanisms underlying complex amplifications.

The scarcity of targetable proteins broadly expressed on cancer cells, but not on healthy cells, is an obstacle for chimeric antigen receptor (CAR)-T cell therapy. Here the authors establish that a functionally impaired version of P2X purinoceptor 7, non-functional P2X7 (nfP2X7), fulfils these criteria, and demonstrate that CAR-T cells targeting nfP2X7 efficiently and selectively kill breast and prostate cancer cells in mouse models.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

In this Resource, Buckley and colleagues profile patients with Crohn’s disease and ulcerative colitis before and after adalimumab therapy. Specific pretreatment differences in the epithelial and myeloid compartments were associated with remission outcomes in both diseases. The authors also describe the cellular circuitry in nonremission patients following treatment.

Between around 5,000 to 2,000 years ago, a drying climate in the vast peatlands of the Congo Basin triggered peat decomposition and carbon release to the atmosphere, implying that this region may be vulnerable to future climate change.

Andrew Wilkie and colleagues report that mutations in TCF12 cause coronal craniosynostosis. They found heterozygous mutations in 38 unrelated families.

Identifying memory and state switching in single cells remains elusive. Here, the authors develop a method, scMemorySeq, by combining cell barcoding and scRNA-seq and apply it to human melanoma cells to track lineages as they switch states between a drug-susceptible state and a state primed for drug resistance.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

The contributions of chirality and conformation as contributing factors to the biological properties of synthetic nanomaterials remain underexplored. A synthesis of bottlebrush polymers with mirror-image side chains has now been developed and it has been revealed that an interplay between side-chain absolute configuration and flexibility influences the biological properties of these polymers both in vitro and in vivo.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

C-SIDE facilitates accurate cell type-specific differential expression analysis for multiple spatially resolved transcriptomics technologies by cell type mixture modeling.

Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

Whole-exome sequencing analysis of 454,787 individuals in the UK Biobank is used to examine the association of protein-coding variants with nearly 4,000 health-related traits, identifying 564 distinct genes with significant trait associations.

The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary cellular responses.

Lysine27-to-methionine mutations in histone H3 genes (H3K27M) occur in a subgroup of gliomas and decrease genome-wide H3K27 trimethylation. Here the authors utilise primary H3K27M tumour lines and isogenic CRISPR-edited controls and show that H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3.

Although it has been widely hypothesized that decisions can be guided by mental simulation of their likely consequences, there has not been direct evidence linking prospection to choices. Here, using fMRI, the authors show that neural representation of future outcomes is related to the choices that participants make.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

The public health burden of dengue is unknown; here cartographic approaches are used to provide insight into the global, regional and national burden of dengue, with the finding that the global number of infections per year is around 390 million, more than three times the estimate of the World Health Organization.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

The protein TRIM28 is identified as a factor that modulates RNA polymerase II pausing and transcriptional elongation at a large number of mammalian genes. This function is regulated by transcription-coupled phosphorylation of TRIM28 at Ser824.

Cataloging microbial genomes from Earth’s environments expands the known phylogenetic diversity of bacteria and archaea.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

H3K36me2 targets DNMT3A to intergenic regions and this process, together with H3K36me3-mediated recruitment of DNMT3B, has a key role in establishing and maintaining genomic DNA methylation landscapes.

Nada Jabado, Jacek Majewski and colleagues identify mutations in multiple histone H3 genes causing recurrent p.Lys36Met alterations in head and neck squamous cell carcinomas. They show that tumors with these p.Lys36Met alterations correspond to a specific DNA methylation cluster along with tumors harboring previously described mutations in NSD1.

The COVID-19 pandemic has demonstrated the need for non-pharmaceutical epidemic mitigation strategies that can be effective even if they are limited in duration. Here, the authors derive analytically optimal and near-optimal time-limited strategies for limiting the epidemic peak in the Susceptible-Infectious-Recovered model and show that, due to the sensitivity of such strategies to implementation errors, timely action is fundamental to non-pharmaceutical disease control.

This Consensus Statement discusses the management of asymptomatic individuals with a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. These individuals are at increased risk of phaeochromocytoma and/or paraganglioma.