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Due to the pulsed nature of X-ray free electron laser (XFEL) instruments the majority of protein crystals, which are injected using continuous jet injection techniques are wasted. Here, the authors present a microfluidic device to deliver aqueous protein crystal laden droplets segmented with an immiscible oil and demonstrate that with this device an approx. 60% reduction in sample waste was achieved for data collection of 3-deoxy-D-manno-octulosonate 8-phosphate synthase crystals at the EuXFEL.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Deep learning was used to map the crown sizes of each tree in the West African Sahara, Sahel and sub-humid zone using submetre-resolution satellite imagery, revealing a relatively high density of trees in arid areas.

In this multi-omics study, the authors identified C1q-dependent synapse elimination by both astrocytes and microglia in Alzheimer’s mouse models. While astrocytes preferentially removed excitatory synapses, microglia preferred inhibitory synapses.

A biased atomic force microscopy tip can write complex in-plane polar topologies in a model ferroelectric Pb_0.6Sr_0.4TiO₃ by means of a smart scan path design. Hence, on-demand generation, reading and erasing of tunable topologies is possible.

The genus Quercus (oaks) has diversified into over 450 species which often play dominant roles in the ecosystems in which they occur. Here the authors present a genome and methylome for a California endemic oak, Quercus lobata, and describe features relevant to its evolutionary success.

Validated barrier inventories and modelling indicate that Europe’s rivers are fragmented by more than one million barriers, such as dams, weirs and fords, causing major impacts on biodiversity.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Observations from the JWST of the second brightest GRB ever detected, GRB 230307A, indicate that it belongs to the class of long-duration GRBs resulting from compact object mergers, with the decay of lanthanides powering the longlasting optical and infrared emission.

Exploring the molecular consequences of exposing mice to social stress, Lyons et al. identify that hippocampal and cortical neurons acquire features of senescence, identifying a mechanism through which the social environment may contribute to aging.

The relationship between the components of repetitive head impacts and chronic traumatic encephalopathy (CTE) remains unclear. Here, the authors use American football helmet sensor data to show that duration of play, cumulative head impacts and linear and rotational accelerations are significantly associated with CTE pathology.

The activity of multiple enzymes is dysregulated in cancer, but this cannot always be measured through enzyme expression. Here, the authors develop methods to measure protease activity across the organism, tissue, and single cell scales, and identify protease dysregulation in lung cancer and its response to targeted therapy.

Guide RNA folding affects functionality of CRISPR-Cas transcriptional control systems. Here, the authors report computational gRNA design together with creation of synthetic CRISPRa promoters for orthogonal expression control and demonstrate the application in pteridine and human milk oligosaccharide production in E. coli.

A database and viewer is described, resulting from the assessment of the carbon stock of over 9 billion individual trees in semi-arid sub-Saharan Africa using field data, machine learning, satellite data and high-performance computing.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Comparison of multiple genome assemblies from wheat reveals extensive diversity that results from the complex breeding history of wheat and provides a basis for further potential improvements to this important food crop.

Analyses of real-world evidence from digital clinical practice data provide important insights for healthcare decision makers. Here, authors test reproducibility of 150 peer-reviewed studies, reporting strong reproducibility, which could be further improved through more complete reporting in future original studies

The actin-based molecular motors, myosins, have also been linked to transcription, but their precise role has remained elusive. Here the authors show RNA polymerase II (RNAPII) is lost from chromatin upon myosin perturbation and that myosin acts as a molecular anchor to maintain RNAPII spatial organisation.

An autophagy receptor, NDP52, is recruited to the nucleus where it can bind DNA. The authors show this promotes changes in chromatin accessibility which supports transcription initiation, providing a direct link between autophagy and transcription regulation.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

Both Earth and Jupiter have equatorial oscillations in their atmospheres. An analysis of over two decades of observations of Saturn's stratospheric emission finds a similar oscillation. The period is 14.8 ± 1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi-annual oscillation.

A powerful coherent diffractive X-ray imaging technique could enable next generation synchrotrons and free-electron lasers to study much larger samples than previously thought possible.

The Na⁺-Cl⁻ cotransporter (NCC) drives salt reabsorption in the kidney. Here the authors determine NCC co-structures individually complexed with the thiazide drug hydrochlorothiazide, and two thiazide-like drugs chlorthalidone and indapamide, revealing that they occlude the NCC ion translocation pathway.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Aegilops sharonensis is a wild diploid relative of wheat. Here, the authors assemble the genome of Ae. sharonensis and use the assembly as an aid to clone the Ae. sharonensis-derived stem rust resistance gene Sr62 in the allohexaploid genome of wheat.

The human monoclonal antibody S2X259 cross-reacts with spike proteins from all clades of sarbecovirus, and provides prophylactic and therapeutic protection in vivo against parental SARS-CoV-2 and emerging variants of concern.

The International Barley Genome Sequencing Consortium reports sequencing and assembly of a reference genome for barley, Hordeum vulgare.

Here the authors address how embryos control the timing of specific gene activation in early frog development. They find transcription factors for early gene activation are maternally loaded and remain at constant levels, and rather that order of activation is based on their sequential entry into the nucleus based largely on their respective affinity to importins.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

In a phase-I/II trial in healthy adults, the BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells against SARS-CoV-2 epitopes that are conserved in a wide range of currently circulating variants.

There is an urgent need of cleaner and energy-efficient technologies for future sustainable chemicals and fuels. Here the authors report the gas phase synthesis of long hydrocarbon chains from atomic carbon and molecular hydrogen precursors in an inert carrier gas, avoiding the use of metal catalysts.

A chromosome-scale genome assembly of rye inbred line ‘Lo7’ provides insights into its incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution and the yield benefits of rye–wheat introgressions.

‘Archaeogenetic analysis of black rat remains reveals that this species was introduced into temperate Europe twice, in the Roman and medieval periods. This population turnover was likely associated with multiple historical and environmental factors.’

Contact-dependent growth inhibition (CDI) is an important mechanism of bacterial competition. Here, Bartelli et al. show that proteolytic processing of a CDI toxin induces a conformational switch required for translocation into target bacteria.

Ice nucleating particles impact the global climate by altering cloud formation and properties, but the sources of these emissions are not completely characterized. Here, the authors show that secondary organic aerosols formed from the oxidation of organic gases in the atmosphere can be a source of ice nucleating particles.

On 1–2 November 2024, the annual Biomarkers of Aging conference welcomed academic and industry scientists, and partners from governmental and nongovernmental organizations, to Harvard Medical School in Boston, USA, to discuss new insights into measuring and monitoring human aging, with the aim of clinical translation. In this Meeting Report, we summarize the conference and offer potential future directions for the Biomarkers of Aging Consortium and the longevity science community at large.

Tumour immune evasion can involve multiple strategies. Here, the authors characterize the immune populations from clinical specimens of lung cancer in conjunction with TCR-β sequencing and show abundant neutrophils affecting cytotoxic T-cell content and the frequent presence of tumour-specific T-cell clones.

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

The ability to manipulate domains in ferroelectrics offers new device opportunities. Compositional and strain gradients in a heterostructure have now been shown to enable the control of ferroelastic domain shape and mobility.

The heterogeneity of whole-exome sequencing (WES) data generation methods presents a challenge to joint analysis. Here, the authors present a bioinformatics strategy to generate high-quality data from processing diversely generated WES samples, as applied in the Alzheimer’s Disease Sequencing Project.

In the Arctic, the risks of the permafrost thaw are perceived differently by communities, and key hazards include infrastructure failure, mobility disruption, decreased water quality and food security, and exposure to diseases, according to a transdisciplinary analysis based on workshops and a thematic network approach.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

SPIRIT 2025 provides updated guidance to authors, reviewers and editors, when preparing clinical trial protocols to enhance their transparency and completeness.