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The microbes responsible for releasing the potent greenhouse gas methane from thawing permafrost remain largely unknown. Mondav and Woodcroft et al. investigate methane flux across a thaw gradient in Sweden and recover a near-complete genome of the dominant methanogen Candidatus ‘Methanoflorens stordalenmirensis’.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

The soil microbiome communicates with plant roots using a chemical language. Here, using p-coumaroyl-homoserine lactone as the synthetic communication signal, the authors demonstrate programmable microbe-to-plant communication from the sender in the soil bacteria to a receiver in the plant.

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.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Despite its great potential, immune checkpoint blockade has shown efficacy in only a restricted number of patients. In this Article, the authors present a nano-based platform for the co-delivery of chemo- and immunotherapeutics that shows efficient synergic antitumour activity in large, hard-to-treat tumour models.

Protein channels are highly selective, but application in membranes is limited due to low protein content. Here, protein channels are embedded into block copolymers to form nanosheets using rapid solvent casting, with better water permeability and similar molecular exclusions relative to other membrane systems.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

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.

The mechanisms regulating stem cells to give rise to human interfollicular epidermis are unclear. Here, the authors use single cell RNA sequencing to identify heterogeneity within the human neonatal interfollicular epidermis and distinct spatial positioning of at least four basal stem cell populations.

How reactive oxygen species regulate neuronal stem cell (NSC) behavior is poorly understood. Here, the authors report that Ncf1-dependent oxidation of Igfbp2 cystines represses DNA repair networks to regulate NSC self-renewal and cell fate decisions.

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.

Glycosylation is an attractive strategy to functionalize natural products and peptides for biomedical use, but non-enzymatic approaches usually require organic solvent and protecting groups. Now, an aqueous phenolic O-glycosylation reaction that uses glycosyl fluoride donors and a calcium salt has been developed for a wide range of substrates, including complex unprotected peptides.

Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.

Garry Cutting and colleagues report a genome-wide association and linkage study for loci that affect lung disease severity in cystic fibrosis. They identify two loci that influence lung function in individuals with cystic fibrosis.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

The controlled manipulation of the topological phases of electronic materials is a central goal of modern condensed matter research. Here, the authors demonstrate controllable switching between two distinct topological phases in a layered ferromagnet via thermal cycling.

A new class of stable, isolable N-silyl oxyketene imines derived from protected cyanohydrins is introduced. Utilization of these nucleophiles in Lewis-base-catalysed aldol additions allows access to either cross-benzoin or glycolate aldol-type products in good yields and exceptional selectivities by simply altering the conditions of the reaction.

Inhibiting alpha-synuclein self-assembly into amyloid structures, associated with Parkinson’s disease, is a potential therapeutic intervention. Here, the authors identify the domains/sequences that are essential for alpha-synuclein aggregation and test the activity of foldamer-based antagonists to identify potential therapeutic targets.

Interferon-ε is a tumour suppressor expressed in the epithelial cell of origin of ovarian cancer, which it restricts by direct action on tumour cells and especially by activation of anti-tumour immunity.

Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

Current methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) that form metastases have several limitations. Here, the authors show an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Whole-genome sequencing analyses of African populations provide insights into continental migration, gene flow and the response to human disease, highlighting the importance of including diverse populations in genomic analyses to understand human ancestry and improve health.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Optical observations of Dimorphos, a satellite of the asteroid 65803 Didymos, before, during and after the impact of the DART spacecraft, from a network of citizen science telescopes across the world are reported.

A large proportion of basal cell carcinomas develop resistance independently of the canonical mutations in genes encoding hedgehog pathway components. An unbiased analysis investigating alternative pathways of resistance uncovers the role of cytoskeletal signaling in driving noncanonical activation of hedgehog signaling through nuclear translocation of SRF and MKL1. These results advance understanding of the mechanisms underlying drug resistance and provide new actionable insights for clinical translation.

Image-based simulation for obtaining physical quantities is limited by the uncertainty in the underlying image segmentation. Here, the authors introduce a workflow for efficiently quantifying segmentation uncertainty and creating uncertainty distributions of the resulting physics quantities.

Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships.

Evidence synthesized from 252 large-herbivore exclusion studies suggests that herbivore-induced change in dominance, independent of site productivity or precipitation, best predicts herbivore effects on biodiversity in grassland and savannah sites.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

After two doses of the BNT162b2 vaccine, virus-specific antibodies and T cells were reduced in patients with solid tumors as compared to individuals without cancer, but neutralizing antibodies increased in most patients who received a third vaccine dose.

The GEMM riboswitch is conserved in diverse bacteria and recognizes the second messenger c-di-GMP which mediates many processes, such as the transition between sedentary and motile behavior. The structure of the GEMM riboswitch with ligand now elucidates ligand recognition and specificity.

Spatial transcriptomics aims to pair omic data with tissue structure. Here the authors report Spatially PhotoActivatable Colour Encoded Cell Address Tags (SPACECAT) to track and isolate live cells by location; this enables spatially informed downstream assays like scRNA-seq and flow cytometry.

Water temperature is a critical variable for lakes, but its spatial and temporal patterns are not well characterised globally. Here, the authors use surface temperature dynamics to define lake thermal regions that group lakes with similar patterns, and show how these regions shift under climate change.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

Disease signatures in high-dimensional biomedical data are detected with a visualization algorithm.

‘The timing and ecological dynamics of extinction in the late Pleistocene are not well understood. Here, the authors use sediment ancient DNA from permafrost cores to reconstruct the paleoecology of the central Yukon, finding a substantial turnover in ecosystem composition between 13,500-10,000 years BP and persistence of some species past their supposed extinctions.’

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

Using a multi-omics approach, the authors examine the molecular drivers of sexual dimorphism in the subcutaneous adipose tissue from sedentary and endurance-trained rats. These data provide a valuable resource for adipose tissue-related research.