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Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

David Ellison and colleagues report whole-genome sequencing of pediatric low-grade gliomas, the most common pediatric brain tumor. They identify a range of genomic alterations, including recurrent and mutually exclusive duplications of the FGFR1 region encoding the tyrosine kinase ___domain and rearrangements of MYB.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

This study shows how including different ancestry groups in a genome-wide association study for prostate-specific antigen levels can improve prostate cancer risk prediction, with implications for population screening.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

Here, a library of more than 300,000 chemicals was screened for activity against Plasmodium falciparum growing in red blood cells. Of these chemicals, 172 representative candidates were profiled in detail; one exemplar compound showed efficacy in a mouse model of malaria. The findings provide the scientific community with new starting points for drug discovery.

At least two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of nuclear factor-κB (NF-κB) signalling, and uncharacterized gene C11orf95; C11orf95–RELA fusion proteins translocate spontaneously to the nucleus to activate NF-κB target genes, and rapidly transform neural stem cells to form tumours in mice

Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3.

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.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

Molecular analyses of newly discovered, embryo-bearing ornithischian and sauropod dinosaur eggs suggest that the ancestral dinosaur egg was soft-shelled, and that hard-shelled eggs evolved independently at least three times in the major dinosaur lineages.

Advances in biofabrication technology enable 3D printed constructs to resemble real tissues, but it remains unclear how cell-generated forces deform these constructs. Here the authors investigate mechanical behaviours of 3D printed “microbeams” made from mixtures of living cells and extracellular matrix.

An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards.

V. cholerae uses its DNA-uptake pili to bind to chitinous surfaces. These filaments also mediate auto-aggregation and, given strain-to-strain variability in PilA (the major pilin subunit), enable discrimination between cells carrying different PilA subunits.

Germline mutations in the Elongator complex gene ELP1 predispose individuals to the development of childhood medulloblastoma.

Whole-genome sequencing of medulloblastoma samples reveals several recurrent mutations in genes not previously implicated in the disease, many of which affect components of the epigenetic machinery in different disease subgroups.

Serotonin has a role in ependymoma tumorigenesis through modifying histones and thereby regulating key transcription factors and activating specific oncogenic transcriptional networks in brain cells.

By studying the effects of salt intake in mice and rats, ShengYu Mu et al. unravel the mechanisms by which dietary salt contributes to hypertension. Salt's prohypertensive effect required the activity of the glucocorticoid receptor in the kidney, which together with sympathetic nervous system activation led to decreased expression of the protein kinase WNK4, a key regulator of sodium channels that regulate blood pressure, via epigenetic regulation.

Here, the authors perform a genome-wide study and identify a genetic variant enriched in the Finnish population that is strongly associated with isolated cleft palate. This finding suggests a genetic basis for the high prevalence of cleft palate in Finland.

Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.

Only about 15% of water cycle diagrams include human interaction with water, although human freshwater appropriation amounts to about half of global river discharge, according to an analysis of 464 water cycle diagrams and a synthesis of the global water cycle.

Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.

Genetic and functional studies implicate allele-specific regulation of OAS1 splicing and nonsense-mediated decay in COVID-19 severity. The OAS1 risk haplotype is also associated with reduced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1.

The retinoblastoma genome is shown to be stable, but multiple cancer pathways are identified that are epigenetically deregulated, providing potential new therapeutic targets.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers and have genetic overlap. Here, the authors use a multi-trait genetic and phenotypic analysis to reveal susceptibility loci for BCC and SCC, and report an optimised polygenic risk score for risk stratification.

Whole-genome sequencing of lung cancer in never smokers identifies different copy number subtypes and shows a lack of tobacco smoking signatures, even in cases exposed to secondhand smoke.

Through genome-wide and focused CRISPR screens, Zhang et al. discover that loss of PRC2 or KMT2D-COMPASS enables distinct EMT trajectories, which exert differential effects on the metastatic capability of carcinoma cells.

An economic analysis suggests that targeting aging offers potentially larger economic gains than eradicating individual diseases. Slowing aging to increase life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion.

Medulloblastomas are the most common malignant childhood brain tumours and are thought to arise from the cerebellum. There is substantial heterogeneity among medulloblastomas and some are thought to arise following aberrant Sonic Hedgehog pathway activation. It is now shown that a distinct subtype of medulloblastoma arises from the dorsal brainstem and is associated with altered WNT signalling. Distinct molecular and clinical profiles of the subtypes have implications for future treatment.