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In addition to canonical guide-dependent endonuclease activity, the Argonaute protein from the archaeon Methanocaldococcus jannaschii (MjAgo) is capable of guide-independent DNA cleavage, enabling MjAgo to process plasmids and genomic DNA.

The spectroscopic and photometric observations of a high-mass, transiting warm Jupiter, TIC 241249530 b, with an orbital eccentricity of 0.94, provide evidence that hot Jupiters may have formed by means of a high-eccentricity tidal-migration pathway.

Here, the authors describe a noncoding genetic variant in GBA1 specific to people of African ancestry that increases the risk of neurodegenerative diseases by interfering with the splicing of mRNA, resulting in lowered protein levels and activity.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Nucleosome positioning and chromatin accessibility are important contributors to the regulation of gene expression. Here the authors describe a method that allows the simultaneous measurement of nucleosome occupancy and chromatin accessibility in the same assay, revealing new features of chromatin organization linked to gene regulation.

A large-scale genomics study shows that the cell of origin and founding mutations determine disease subtype and lead to the expression of multiple haematopoietic lineage-defining antigens in mixed phenotype acute leukaemia.

This study identifies candidate safeguard repressor transcription factors that repress alternate lineages in mature cell types and provides functional evidence that Prox1 performs such a function in hepatocytes during reprogramming, regeneration and in cancer.

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 a broad cross-tissue analysis, the authors show that a receptor called EDA2R steadily increases with age in both humans and animal models, and becomes even more active in conditions like obesity and diabetes, intensifying inflammation-like processes in muscle cells.

As part of the modENCODE initiative, which aims to characterize functional DNA elements in D. melanogaster and C. elegans, this study presents a genome-wide chromatin landscape of the fruitfly, based on 18 histone modifications. Nine prevalent chromatin states are described. Integrating these analyses with other data types reveals individual characteristics of different genomic elements. The work provides a resource of unprecedented scale for future experimental investigations.

The first near-infrared image of a dust ring around a young nearby star has been taken by an instrument aboard the Hubble Space Telescope. The image was made possible by blocking out the star's glare, and the narrowness of the revealed ring implies that it is being gravitationally confined by companion bodies.

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.

Proteome-wide measurements of dose–response curves for 144 drugs reveal drug mechanisms of action.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Aircraft measurements over the Amazon show that new particle formation in the upper troposphere emerges when isoprene, emitted by forests, undergoes oxidation in the presence of nitrogen oxides produced by lightning.

This study assessed COVID-19 social science preprints’ replicability using structured groups. Both beginners and more-experienced participants used a elicitation protocol to make better-than-chance predictions about the reliability of research claims under high uncertainty.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Sarcomeres, the building blocks of striated muscles, comprise ordered actomyosin arrays involved in force production. Here, the authors visualize sarcomere organization in neonatal cardiomyocytes with in situ cryo-electron tomography, revealing a reduced order of the thin filaments, their sliding and functional states enabling contraction.

HLA-DM interacts with MHCII and promotes peptide exchange. This activity of HLA-DM is regulated by HLA-DO. The crystal structure of the HLA-DO–HLA-DM complex along with mutagenesis and kinetic analyses reveal that HLA-DO adopts a classical MHCII structure and competitively inhibits HLA-DM's activity on MHCII.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

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 large-scale, five-year study in Indonesia finds that enriching oil palm-dominated landscapes with patches of trees bolsters biodiversity and ecosystem functioning without impairing oil palm yields but should not replace forest protection.

A monoclonal antibody that binds NINJ1 and inhibits NINJ1 oligomerization prevents plasma membrane rupture in dying cells, resulting in decreased inflammation of surrounding tissue in mice.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

During embryo development, cell fitness determines survival but how this is regulated is unclear. Here, the authors show that in early embryonic development and stem cells exiting the naive state, cells sense the fitness of their neighbours and trigger p53 to repress mTOR to eliminate a third of cells.

A single-cell-based approach allows the daughters of a damaged cell to be separately tracked following single mitotic events. This technique highlights the different ways in which ultraviolet light and reactive oxygen species cause mutagenesis.

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. Here the authors demonstrate that hematopoietic stem cells with short telomeres induced by mutations affecting telomerase complex genes undergo differentiation towards megakaryopoiesis through the activation of the IFI16-mediated interferon response.

Progressive respiratory failure is the primary cause of death in patients with COVID-19, but pathologies in other tissues may also occur. Here the authors report that adrenal tropism of SARS-CoV-2 is associated with adrenalitis, reduced adrenal cortisol levels and severe adrenal damage in a post-mortem case series of patients with severe fatal COVID-19.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Extensive characterization of the stem and progenitor cell hierarchies of myelodysplastic syndromes reveals compensatory survival mechanisms underpinning the failure of hypomethylating agents, and uncovers biomarkers that predict second-line clinical response to venetoclax-based therapy.

In a phase 2 trial, the oral type II RAF inhibitor tovorafenib exhibited an overall response rate of 67% in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma.

To model hepatocyte function accurately in vitro, it is necessary to generate and maintain a polarized epithelium. Here, the authors describe a protocol to generate polarized human pluripotent stem cell-derived hepatocyte-like cells (HLCs) to model enteric virus production and drug secretion in vitro.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Caspases are known for their role in cell death, but they can also participate in other physiological functions without killing the cells. Here the authors show that unique caspase adaptor proteins can regulate caspase activity within mutually-exclusive and independently regulated subcellular domains.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

Plasmodium-infected red blood cells export virulence factors, such asPfEMP1, to the cell surface. Here, the authors identify a protein complex termed EPIC that interacts with PfEMP1 during export, and they show that knockdown of an EPIC component affects parasite virulence.

Here the authors report the structure of the human 20S U5 snRNP, providing new insights into the assembly of the spliceosome building blocks.