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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.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Formic acid is a potential hydrogen carrier, although practical schemes to achieve its dehydrogenation are still rare. Here the authors introduce a stable and efficient ruthenium 9H-acridine pincer complex able to catalyse the additive-free dehydrogenation of neat formic acid, generating even high pressures of H₂ and CO₂ in a closed system.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

The ability to rationally remodel enzyme conformational landscapes to modify catalytic properties is limited. Here, the authors, using a computational procedure, redesign the conformational landscape of an aminotransferase to stabilize a less populated but reactive conformation and thereby increase catalytic efficiency with a non-native substrate.

Changes in residual protein entropy are a potentially important component of the change in the free energy of protein association, but such thermodynamics have been virtually impossible to determine experimentally. Here the authors used solution NMR spectroscopy to show that the change in internal dynamics of calmodulin varies significantly on binding a variety of target domains, which indicates that changes in residual protein conformational entropy can contribute significantly to the free energy of protein-ligand association.

A global map of human subcellular architecture yields protein complex structures, reveals protein functions, identifies assemblies with multiple localizations or cell-type specificity and decodes paediatric cancer genomes.

Global diversity trends in the fossil record vary regionally through time and space, affecting our ability to interpret macroevolutionary history. Here, the authors propose a method to eliminate spatial sampling bias, estimate origination and extinction rates, and generate diversity estimates, applying this method to the Late Permian to Early Jurassic marine fossil record.

Polanía et al. show that, similarly to sensory signals, subjective preferences guiding choice are represented by the brain in a manner that accounts for regularities of the environment, thereby optimizing use of limited neural processing resources.

QSIPrep is a software platform for processing of most diffusion MRI datasets and ensures that adequate workflows are used.

Interlocked shape-persistent organic cages are rare structures and the majority are formed using π-stacking as the driving force. Now it is shown that weak dispersion interactions—which are modulated by changing the 1,4-substituents of the constituent dialdehyde linkers—can be used to form interlocked dimeric and trimeric catenated cages.

Phosphonated polymers have been proposed as anhydrous proton conductors for fuel cells but anhydride formation of phosphonic acid functional groups lowers conductivity. A synergistically integrated phosphonated poly(pentafluorostyrene) is shown to maintain high protonic conductivity above 200 °C.

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.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

This paper highlights the far-red chemigenetic H₂O₂ reporter oROS-HT₆₃₅, which enables detailed insights into intricate intracellular and intercellular H₂O₂ dynamics, along with their environmental interactants, through spatially resolved, multiplexed real-time H₂O₂ imaging.

Cyclic molecules often exhibit unusual properties; consider for example the resonance stabilization energy of benzene or the strong cation binding of crown ethers. Now, a family of rings comprising varying numbers of directly linked ferrocenes has been prepared. These compounds are highly symmetric in solution and undergo rapid ‘oxidation-state isomerism’ when charged.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.

Here, the authors present a TWAS framework OTTERS that adapts multiple polygenic risk score methods to estimate eQTL weights from summary-level eQTL data. Both simulation and real studies show OTTERS is powerful across a wide range of genetic architectures.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Key mechanistic steps for selective CO₍₂₎ reduction over Cu into hydrocarbon versus oxygenated C₂ products are identified by atomistic and microkinetic modeling. Variations in C and OH binding are found to predict catalytic selectivity of materials.

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.

Following the building principles of crown ethers for cation encapsulation, inverse crowns are rings of metals that bind anions. Now a redox-active inverse crown ether featuring Na⁺ cations and Mg⁰ has been shown to reduce epoxides, N₂O, S₈ or O₂ by combining anion complexation by the ring of metal cations with the reducing power of Mg⁰.

Tiled amplicon sequencing is an essential tool for tracking the spread and evolution of pathogens, including SARS-CoV-2, however existing methods for tiled amplicon design require slow and costly downstream manual optimization. Here the authors present Olivar, a first step towards fully automated, variant-aware design of tiled amplicons for pathogen genomes.

BayesR3 samples the polymorphisms affecting complex traits at reduced computational cost to predict the genetic value, breeding value, or individual risk of genotypes.

The authors report the mutational landscape of 29 cell types from microdissected biopsies from 19 organs and explore the mechanisms underlying mutation rates in normal tissues.

The quantum critical point associated with the antiferromagnetic spin-density wave transition occurs in many strongly correlated systems. Here the authors study this quantum critical point in a 2D spin-fermion model using an efficient hybrid Monte Carlo method and make predictions for future experiments.

Charge transfer in DNA is of fundamental interest in chemistry and biochemistry and has possible applications in nano-electronics. Now it has been shown, through a combined experimental and theoretical study, that the migration of positive charges through low-lying orbitals of nucleobases (deep-hole transfer) leads to charge transfer that is faster than previously considered transport regimes.

The exoplanet HD 189733b has a metal-enriched atmosphere with the possible presence of H₂O (13.4σ), CO₂ (11.2σ), CO (5σ) and H₂S (4.5σ).

Analysis of gravitational waves from merging binary neutron stars was accelerated using machine learning, enabling full low-latency parameter estimation and enhancing the potential for multi-messenger observations.

Zeolites are industrially important materials, functioning as separation media and catalyst supports. Here, the authors use a large-scale, multi-step computational screening process to identify promising zeolites for challenging separations, namely ethanol purification and alkane adsorption.

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.

Whole-brain anatomical and activity surveys identify the lateral hypothalamus as a key driver of recovery from spinal cord injury, leading to a deep brain stimulation therapy that augments the recovery of walking in humans.

Organic biocrystals play crucial roles in biological processes and diseases, yet the molecular mechanisms of their formation remain poorly understood. Here, the authors reveal that hematin crystal nucleation in malaria parasites follows a nonclassical pathway and can be modulated by solute-modifier interactions, offering a strategy to control crystal formation in a variety of systems, including for malaria treatment.

Fe–N–C catalysts are a promising alternative to precious metals in fuel cell cathodes, but they suffer from durability issues. Now, a preparation method is reported that allows increasing the active site density while also improving durability.

Here, the authors show that cystatin C (CST3) regulates the activity of cathepsin B during pancreatitis in a pH dependent manner. Moreover, cathepsin B activity is inhibited by monomeric CST3 but activated by dimeric CST3.

It is promising but elusive to use covalent organic frameworks (COFs)-based chromatic sensors for chemical tomography – or the 3D spatial mapping of chemical details within living systems. Here, the authors report a COF-silk fibroin microneedle interface capable of 3D mapping of the chemical environment at standoff distances from the plant, enabling in-vivo chemical tomography.

DEED captures the balance between entropy gains and costs, allowing the correct classification of functional synthesizability of multicomponent ceramics, regardless of chemistry and structure, and provides an array of potential new candidates, ripe for experimental discoveries.