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If we don’t slow down, the research enterprise is going to crash, argues Adrian Barnett.

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

Dierl, Hinsen et al. investigate long term pulmonary toxicity in pediatric cancer survivors by the use of Free-breathing phase-resolved functional lung (PREFUL) MRI on a low-field system. Subclinical and time-dependent reduction in pulmonary ventilation and perfusion is revealed.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

Using a mouse model with a macrophage-specific DNA repair defect, Niotis, Arvanitaki et al. identify DNA damage-induced autophagy in macrophages as a link from aging to autoimmunity.

Carbapenems are last-resort antibiotics, but resistance is rising due to hydrolyzing enzymes called carbapenemases. The authors present a machine learning algorithm and web-app to rapidly predict carbapenemase-production in Enterobacterales.

Time-resolved serial femtosecond crystallography at X-ray free-electron lasers is a powerful approach for studying macromolecular dynamics, but its widespread use is limited by high sample consumption. Here, the authors introduce a segmented-droplet mix-and-inject strategy at the European XFEL that reduces sample consumption by up to 97% while preserving the data quality required for time-resolved structural studies of the enzyme NQO1.

The authors report on engineering metazoan fatty acid synthase variants with tunable selectivity to obtain short- and medium-chain fatty acids, alcohols and aldehydes. Pairing these optimized enzymes with a yeast strain designed for efficient β-oxidation yields high production levels of medium-chain fatty acids.

The R21/Matrix-M vaccine, but not the ME-TRAP vaccine, was protective against intradermal challenge with Plasmodium falciparum sporozoites, while neither was protective against direct venous inoculation, potentially explaining previously observed differences in protection.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

A hybrid machine learning and atomistic modelling strategy enables one-shot design of efficient enzymes to catalyse diverse biological and non-biological chemical transformations.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

Having a good mentor early in your career can mean the difference between success and failure in any field. Adrian Lee, Carina Dennis and Philip Campbell look at what makes a good mentor.

A material’s internal structure is known to dictate its macroscopic properties through structure-dependent particle dynamics, as exemplified by the so-called de Gennes narrowing. Through experiments and simulations on soft colloid suspensions, the authors reveal a breakdown of this correlation, showing that the q-dependent relaxation time remains unchanged across length scales and that single-particle elasticity facilitates structure-independent relaxation.

This scenario study investigates how the EU net-zero target can be reached with varying levels of residual fossil fuels. Reducing fossils by only 90% relies on substantial carbon storage, while a full fossil phase-out requires a rapid scale-up of expensive carbon-neutral e-fuels.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

DNA damage can arise from natural cellular processes, but how cells prevent resulting mutations is unclear. Here, the authors show that the enzyme Polκ protects mouse tissues from mutations caused by endogenous guanine lesions, revealing how DNA repair and damage tolerance pathways cooperate to maintain genome integrity.

A species-level dataset of sediment-dwelling macrofauna, sampled 2 years before and 2 months after a test of a commercial deep-sea mining machine, reveals losses of macrofaunal density and species richness within the machine’s tracks and community-level effects in both the tracks and an area impacted by sediment plumes.

Optimizations of X-ray nanotomography including the choice of resin allows high-resolution imaging of mouse brain tissue, approaching the resolution of volume electron microscopy. Since it does not require slicing the tissue, this technology may become an attractive alternative to current standard methods for connectomics.

The extent to which in-vitro cellular experiments are effective models for complex biology underlying human phenotypes is often unclear. Here the authors propose and implement a framework using gene perturbation data to evaluate in-vitro models.

Omnivores like bears can switch between plant and animal diets, potentially helping them respond to changing conditions. By combining modern and fossil data, this study shows that bears shift toward carnivory in harsher climates and toward herbivory in more productive environments.

Targeting two distinct steps of the transcription process yields synergistic antibiotics that kill non-replicating Mycobacterium tuberculosis and reduce drug resistance.

Chaperone-mediated autophagy declines with age in skeletal muscle of humans and mice, leading to muscle dysfunction characterized by impaired calcium homoeostasis and mitochondrial function.

PropMolFlow is a flow-matching method for property-guided molecule generation that matches diffusion model performance while generating stable, valid structures more quickly and enabling the discovery of molecules with under-represented property values.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

This study presents a BRET biosensor that measures how anticancer drugs cooperatively engage PRMT5 complexes in cells, revealing how cellular metabolites such as SAM and MTA enhance drug action and enable precision therapies for MTAP-deleted tumors.

Microglia can alter their properties to adopt a wide spectrum of cellular phenotypes. Here, the authors show that remodeling of microglial mitochondria accompanies microglial responses to challenges and aging, and provide evidence that these organelles play a role in regulating basal microglial morphology, gene expression, and inflammatory profile.

Immunotherapy is at an inflection point. After three decades of accelerating progress, immunotherapy is entering the realm of in vivo engineering. This Comment discusses the potential of in vivo engineering in addressing challenges met by ex vivo engineering efforts. Per a recent workshop organized by the National Institutes of Health, we highlight progress, the platform technologies fueling it, and elements of a road map and challenges ahead.

Here, the authors break the symmetry of atomically thin transition metal dichalcogenides using a tunable uniaxial strain, and demonstrate pseudospin analogs of spintronic phenomena such as the Zeeman effect and Larmor precession.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

The strategic placement of sulfur within a nickel porphyrin complex coupled with copper facilitates efficient electrochemical CO₂ reduction to ethylene and ethanol.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

AQuaRef employs machine learning to refine protein structures from cryo-EM and X-ray data in Phenix. It achieves quantum-level precision, improving model geometry and fit to the data while reducing overfitting.

ICeChIP (internally calibrated ChIP) uses spiked-in, defined nucleosomal standards to overcome the pitfalls of traditional ChIP experiments, enabling the measurement of antibody specificity and the absolute measurement of histone modification density at genomic loci.

A framework is presented to extrapolate the range of behaviors for influenza antibodies. Using this basis set of behaviors, the collective action of multiple antibodies can be teased apart to describe the individual antibodies within.

Herpesvirales utilize a unique nuclear egress route for capsid export. Here the authors show that herpesviruses exploit a cellular membrane protein, once thought to transport chloride, to facilitate membrane fusion and egress from the nucleus.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Many different models are used in research into diabetes mellitus, and each has strengths and limitations. In this Review, the authors explain several in vivo and in vitro models of hyperglycaemia and discuss how future models might be improved to better replicate physiological conditions in people with diabetes mellitus.

The role of ecological factors in modulating the spread of antibiotic-resistance bacteria in the gut remains unclear. Here, the authors use anaerobic microcosms to study the population growth of four clinical E. coli strains in the gut microbiome.

Zamboni et al. reveal how enhancers encode cell-type-specific responses to CNS injury. By combining multiomic profiling, deep learning and in vivo screening, they uncover injury-responsive enhancer logic and enable targeting of reactive astrocytes.