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In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

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.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

CAR T cells targeting PSMA and engineered to be resistant to immunosuppressive TGFβ signaling exhibit dose-dependent toxicity and expansion following infusion, with some transient antitumor activity, in patients with metastatic castration-resistant prostate cancer

THOC6 is required for TREX tetramer formation. Analysis of pathogenic THOC6 variants differentiate the conserved mRNA export functions of TREX dimers and RNA processing functions of TREX tetramers underlying THOC6 Intellectual Disability Syndrome.

Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Reliable detection of mutations below 0.5% variant allele frequency remains a key challenge for circulating tumor DNA sequencing assays.

Very early observations of a type Ia supernova—from within one hour of explosion—show a red colour that develops and rapidly disappears. These data provide information on the initial explosion mechanism: surface nuclear burning on the white dwarf or extreme mixing of the nuclear burning process.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Genome-wide and multitrait analyses identify novel loci associated with hypertrophic cardiomyopathy and relevant left ventricular traits. Gene-level burden analyses show that rare truncating SVIL variants are associated with high risk of hypertrophic cardiomyopathy.

On the Nansen Ice Shelf in Antarctica, a surface river that terminates in a waterfall can drain the ice shelf’s entire annual meltwater in just one week, potentially preventing the meltwater from hastening the catastrophic collapse of the shelf.

The flavoenzyme nicotine oxidoreductase degrades nicotine in the bloodstream. Now, genetic selection in bacteria has been used to improve the catalytic performance of nicotine oxidoreductase, isolating variants with increased O₂ reactivity that were more effective at degrading nicotine in the blood of rats.

Here, the reaction of the suicide inhibitor sulbactam with the M. tuberculosis β-lactamase (BlaC) is investigated with time-resolved crystallography. Singular Value Decomposition is implemented to extract kinetic information despite changes in unit cell parameters during the time-course of the reaction.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Adalatherium hui, a newly discovered gondwanatherian mammal from Madagascar dated to near the end of the Cretaceous period, shows features consistent with a long evolutionary trajectory of isolation in an insular environment.

S1P₁ is a sphingosine phosphate receptor expressed on lymphocytes. Han and colleagues show that phosphorylated S1P₁ accumulates in brain lesions of patients with multiple sclerosis. Similarly, mice bearing mutant S1P₁ develop more severe experimental autoimmune encephalomyelitis.

The high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy, which both imply a super-Chandrasekhar mass progenitor.

Resource constraints and environmental impacts associated with current phosphorus fertilizer manufacture and use highlight considerable risks within global food production systems. Research portfolios targeted at existing soil phosphorus reserves might offer a solution.

Crowdsourcing analysis improves computational prediction of cytotoxic responses in humans.

The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

2024 saw multiple high-impact compound events. Record-breaking global temperatures combined with regional weather variability to create compound floods, spatially compounding droughts and heatwaves, and hazard sequences with often devastating impacts.

Serial femtosecond X-ray crystallography permits the use of very small protein crystals; however, a continuous flow of sample is required. Weierstall et al. design and demonstrate an injector system that can supply microcrystals in the lipidic cubic phase, dramatically reducing the quantities of protein required.

Ionizing radiations (IRs) cause widespread genomic damage and can, through unknown mechanisms, lead to changes in chromosome numbers by perturbing the cells undergoing mitosis. Here, the authors investigate the potential mechanism behind the increased susceptibility of mitotic cells to IRs.

Synthetic transcriptional repressors are engineered from natural DNA-binding domains.

Retinal pigment epithelial cells are identified as a local source of insulin in the retina, which is stimulated by phagocytosis of photoreceptor outer segments and starvation and has the potential to influence retinal physiology and disease.

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.

This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.

Evolutionary modelling and expert review are applied to integrate experimentally supported knowledge accumulated in the Gene Ontology knowledgebase to create a draft human gene ‘functionome’.

Early social experience can alter epigenetic patterns and stress responses later in life. A study on wild spotted hyenas finds that maternal care and social connections after leaving the den influence DNA methylation and contribute to a developmentally plastic stress response.

The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing.

The genetic changes that occur in late stage metastatic melanoma are not well delineated. Here, the authors use rapid autopsy samples from metastatic melanoma patients and show that the late stage in the disease is characterised by whole genome doubling and aneuploidy.

Gene expression, alternative splicing and DNA methylation profiles from human kidney samples provide insights into the effects of common variants influencing blood pressure. Mendelian randomization uncovers the effects of blood pressure on renal outcomes.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

Sepsis is characterized by deregulated host response to infection. Efficient therapies are still needed but a limitation for sepsis treatment is the heterogeneity in patients. Here Sweeney et al. generate prognostic models based on gene expression to improve risk stratification classification and prediction for 30-day mortality of patients.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

The unique properties of 2D materials are affected by the discontinuities posed by the structure’s edge. Here, using atomic-resolution scanning transmission electron microscopy and ab initio molecular dynamics simulations, the authors image and explain the formation of specific edge structures on Mo_{1 − x} W _x Se₂ monolayers under different chemical conditions.