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Bicyclic hydrocarbons, and bicyclo[1.1.1]pentanes in particular, are playing an emerging role as saturated bioisosteres in pharmaceutical, agrochemical and materials intramolecular coupling approach has been developed for the modular construction of underexplored multisubstituted strained bicyclic hydrocarbons, ranging from [1.1.1] to [3.2.1] scaffolds.

The high-pressure nature of the core-forming process led to the Earth's core being richer in low atomic number elements, notably silicon and possibly oxygen, than the smaller planetesimal building blocks would indicate.

Did the cenancestor have a phospholipid membrane? In this Opinion article, Lombard, López-García and Moreira discuss how recent top-down phylogenomic analyses have provided new information to address this question.

Brain-machine interfaces are hindered by neuroinflammation. Here, the authors found that bacterial sequences invade the brain post-microelectrode implantation. Antibiotic-treated mice showed reduced bacterial presence and altered neuroinflammatory profile, temporarily improving recording performance.

Mutations in profilin 1 (PFN1), which modulates actin dynamics, are associated with ALS. Here the authors show that expression of ALS-PFN1 is sufficient to induce deficits in human microglia-like cells, including impaired phagocytosis and lipid metabolism, and that gain-of-function interactions between ALS-PFN1 and PI3P may underlie these deficits.

Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2^E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2^E76K to its closed, autoinhibited conformation.

Information on the occurrence of aneuploidies in prehistory human populations are rare. Here, from a large screen of ancient human genomes and osteological examination, the authors find genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome) in historic and prehistoric infants.

The two homoeologous subgenomes in the allotetraploid frog Xenopus laevis evolved asymmetrically; one often retained the ancestral state, whereas the other experienced gene loss, deletion, rearrangement and reduced gene expression.

Amphetamines are known to enhance extracellular dopamine levels, but the underlying mechanisms are unclear. Utilising a new pH biosensor for synaptic vesicles, the authors show that amphetamines diminish vesicle pH gradients, disrupting dopamine packaging and leading to increased neurotransmitter release.

Excesses of ¹⁴²Nd previously found in 3.7-billion-year-old rocks from Isua, southwest Greenland, imply their derivation from a depleted mantle formed in the Hadean eon; the signature of a complementary Hadean enriched reservoir is now reported in 3.4-billion-year-old mafic dykes found in Isua.

An example of hybrid incompatibility between maize and teosinte reveals a selfish toxin–antidote system mediated by small RNAs that may have contributed to the origin of maize.

Aberrant thymocyte developmental programming results when interactions between thymic stroma and pre-T cell receptors occur in the absence of major histocompatibility complex bound to antigen peptide.

V1298 Tau b is a 20–30-Myr-old Jovian-sized planet with a haze-free, metal-poor atmosphere and a potentially hot interior. These properties suggest that V1298 Tau b formed in situ via pebble accretion and that it is still evolving and likely to become a Neptune- or sub-Neptune-sized planet.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Resistance to EGFR inhibitors presents a major obstacle in treating non-small cell lung cancer. Here, the authors develop a recommender system ranking genes based on trade-offs between diverse types of evidence linking them to potential mechanisms of EGFRi resistance.

An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.

In Parkinson’s disease (PD) the monomeric protein alpha-synuclein (aSyn) misfolds and aggregates into insoluble fibrils. Here the authors use NMR measurements and hydrogen–deuterium exchange mass spectrometry and find that the more solvent exposed the N-terminus of aSyn is, the more aggregation prone its conformation becomes, and further show how PD mutations and post translational modifications influence the extent of the N-terminus solvent exposure.

New reference genomes of the two extant monotreme lineages (platypus and echidna) reveal the ancestral and lineage-specific genomic changes that shape both monotreme and mammalian evolution.

Palaeoproteomics offers an opportunity to resolve molecular phylogenies especially in contexts where ancient DNA does not preserve. Here collagen sequences resolve sloth phylogenies differently from morphology-based estimates, illuminating the utility of proteomics in systematics.

Mosses are a highly diverse lineage of land plants. Here, the authors provide a detailed phylogeny of 29 orders of moss, using nuclear and organelle data to provide robust hypotheses for most of the ordinal moss relationships.

Williams et al. show that structural and functional brain asymmetry is already seen in the newborn brain, but that adult patterns of brain asymmetry are not fully developed.

New and existing age data show active arc processes in Southern California during the beginning of the Laramide orogeny, which require a two-stage process and challenge the oceanic plateau collision paradigm.

The division of the immune system into innate and adaptive arms has become blurred in recent years. Kuka et al.identify a novel population of αβ-T-cell receptor-expressing cells in mice and humans that both presents and responds to antigen and produces interleukin-12, thus exhibiting core properties of both dendritic cells and T cells.

A cell-culture method involving decellularized tissue scaffolds enables the spontaneous formation of cell colonies that phenotypically recapitulate in vivo organ-specific cancer metastases.

Crocodylians and their relatives have a rich evolutionary history. Here the authors show long-term decline of terrestrial crocodylians driven by decreasing temperatures but no relationship between temperature and biodiversity for marine crocodylians over their 250 million year history.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

Cryptic pockets enable targeting of proteins currently considered undruggable because they lack pockets in their ground state structures. Here, the authors develop a graph neural network that accurately predicts cryptic pockets in static structures by training using molecular simulation data alone.

The dust in the dust coma of interstellar object 2I/Borisov is large (exceeding ~1 mm radius) and compact, differing from the fluffy aggregates typically found in Solar System comets. This compact dust is presumably a result of impacts in the comet’s home system, and suggests 2I/Borisov formed in a collapsing pebble cloud.

The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues.

Imaging mass cytometry of the human lung reveals the cellular composition and spatial architecture during COVID-19 and other acute injuries, enabling the characterization of lung pathophysiology from structural, immunological and clinical perspectives.

Group 2 innate lymphoid cells (ILC2s) are generally considered to have pro-tumor functions. However, Belz and colleagues demonstrate that ILC2s have anti-melanoma effects due to their high production of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor in the tumor microenvironment.

A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.

The molecular mechanisms underlying contextual fear memory consolidation by sparse dentate gyrus (DG) neuronal populations remain unclear. Here using unbiased RNA sequencing of DG engram neurons the authors identify persistent transcriptome modifications during memory consolidation, in which CREB-dependent transcription features prominently

Margaret Goodell, Wei Li and colleagues report conditional ablation of the Dnmt3a DNA methyltransferase in hematopoietic stem cells (HSCs) in mice. They show that Dnmt3a is critical for epigenetic silencing of HSC regulatory genes and for HSC differentiation.

Plant root hairs elongate in response to low soil phosphate. Here Bhosale et al. show that root hair elongation requires auxin synthesis mediated by TAA1, auxin transport by AUX1 in the lateral root cap and epidermis, and signaling via the auxin-inducible ARF19, RSL2 and RSL4 transcription factors.

ARID1A is frequently mutated in ovarian clear-cell carcinoma. Here the authors show that ARID1A loss in mice cooperates with PI3K activation to recapitulate the human disease, and implicate IL-6 signalling as the underlying mechanism.

Prostate cancer is a common cause of male cancer-related deaths. Complete sequencing of prostate cancer genomes now reveals previously unknown balanced rearrangements. Single-nucleotide resolution afforded by sequencing indicates that complex rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.

Douglas Easton and colleagues report a comprehensive analysis of SNP associations to prostate cancer across the 8q24 region. They report 8 SNPs in 5 blocks independently associated to prostate cancer risk.

Hepatocyte nuclear factor 4 alpha (HNF4α) is regulated by different promoters to generate two isoforms, one of which functions as a tumor suppressor. Here, the authors reveal that induction of the alternative isoform in hepatocellular carcinoma inhibits the circadian clock by repressing BMAL1, and the reintroduction of BMAL1 prevents HCC tumor growth.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Devant and Kagan review the biochemical and cell biological mechanisms that control gasdermin D pore-forming activity and its diverse downstream immunological effects.

TFG-1 is identified as a regulator of COPII coat assembly that interacts with SEC-16 to control protein exit from the endoplasmic reticulum. TFG–kinase fusion proteins have been detected in some cancers and might promote oncogenesis by prematurely phosphorylating target substrates as they exit the endoplasmic reticulum.