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The impact of late Pleistocene climate change on ecosystems has been hard to assess. Here, the authors sequence ancient DNA from Hall’s Cave, Texas and find that both plant and vertebrate diversity decreased with cooling, and though plant diversity recovered with rewarming, megafauna went extinct.

A study shows that the rapid diversification of cichlids in African lakes is driven by their ability to evolve between having simple or complex teeth.

Protection afforded by inorganic minerals is assumed to make mineral-associated organic carbon less susceptible to loss under climate change than particulate organic carbon. However, a global study of soil organic carbon from drylands suggests that this is not the case.

The chronology and mode of parallel evolution remain unclear. Here, the authors compare mid-Holocene and contemporary bottlenose dolphin adaptations between pelagic and coastal ecosystems with paleogenomics, finding rapid adaptation to newly emerged habitat from standing genetic variation.

Deep learning frameworks require large human-annotated datasets for training and the resulting ‘black box’ models are difficult to interpret. Here, the authors present Kartezio; a modular Cartesian Genetic Programming-based computational strategy that generates fully transparent and easily interpretable image processing pipelines.

A decline in disruptive science and technology over time is reported, representing a substantive shift in science and technology, which is attributed in part to the reliance on a narrower set of existing knowledge.

Directed evolution uses laboratory-based evolution to enhance the properties of biomolecules, primarily to generate proteins with optimized or novel activities. This Review discusses the diverse range of technologies for the directed evolution of proteins, particularly methods for generating diversity in the gene library and approaches for screening and selecting for variants with desired properties. The relative strengths and limitations of these approaches are highlighted to guide readers to appropriate strategies.

By demonstrating a computational approach to restore the clinical efficacy of a COVID-19 antibody, the potential to rapidly update clinical antibodies is explored.

The cellular origin of human pancreatic ductal adenocarcinoma (PDAC) is still unclear. Here the authors used human primary acinar and ductal cells to successfully reconstitute PDAC tumorigenesis from both lineages and revealed transcriptional changes during early PDAC progression.

Cells survive starvation by activating protective pathways. Here, the authors describe that kinase EFK-1/eEF2K defends against oxidative damage in long term starvation in C. elegans independently from its kinase activity and translation regulation.

Evidence suggests that fibrous aggregates of protein tau may be the proximal cause of Alzheimer’s disease. Here, using atomic structures of tau fibrils from brains of people with Alzheimer’s disease, the authors have found small-molecule drug leads that disaggregate tau fibrils in vitro.

Contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low biomass environments. Here the authors describe Squeegee, a computational approach designed to detect microbial contamination within low microbial biomass microbiomes and identify microbial contaminants in publicly available datasets that lack negative controls.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

Studies of brain network development typically focus on a single scale. Here, the authors derived personalized functional networks across scales, and find that network development systematically adheres to and strengthens hierarchical cortical organization.

The antiphage defence protein CapRel^SJ46 in Escherichia coli can directly bind and sense two completely unrelated and structurally different proteins using the same sensory domain, with overlapping but distinct interfaces.

The plasma membrane’s electrical potential is maintained by ion channels, though the impact of this potential on cell fate has not been clearly elucidated. Here they show that changes in membrane potential can affect calcium levels and mTOR in pluripotent stem cells, altering their transition from pluripotency to differentiation.

Lim et al. identify CD34 as a surface marker of the heart’s sinoatrial node pacemaker cells, enabling their isolation from stem cell differentiation cultures, advancing future disease modeling, drug discovery, and biological pacemaker applications.

Combining geographic information, climate data and colour mechanism at broad phylogenetic and spatial scales, the authors determine how transitions between pigmentary and structural colours influence bird speciation dynamics.

Peripheral artery disease is a vascular disorder characterized by narrowing of the peripheral arteries owing to atherosclerosis or thrombosis. In this Primer, Aboyans and colleagues review the epidemiology, pathophysiology, diagnosis and management of peripheral artery disease, and discuss areas for future research.

A high-throughput chemical–genetic screening approach for the discovery of targets and chemicals to treat Mycobacterium tuberculosis yields tenfold more hit compounds than conventional whole-cell screening methods.

In this study, three individuals with tetraplegia designed vivid, reliable and object-appropriate sensations with a variety of tactile characteristics using self-selected stimulus parameters that stimulated their somatosensory cortex upon digital object contact

mBrainAligner is a cross-modal registration platform for whole mouse brains imaged with different modalities. In addition, a fluorescence micro-optical sectioning tomography-based mouse brain atlas has been generated.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.

A discussion of some of the challenges and promise of single-cell technology.

Artificial neural networks (ANNs) are vulnerable to subtle adversarial perturbations that yield misclassification errors. Here, behavioral studies demonstrate that adversarial perturbations that fool ANNs similarly bias human choice.

Intravitreal administration of the antisense oligonucleotide sepofarsen in patients with Leber congenital amaurosis type 10 showed a manageable safety profile, ocular adverse events being dose dependent, and achieved meaningful improvements of visual function.

Calculations of relative binding free energy are crucial for lead optimization in structure-based drug design, but classical methods are computationally expensive. Here, the authors describe a more efficient method for calculating the free energy that is as accurate as thermodynamic integration.

New Guinea highlands are highly diverse, yet the patterns of colonization and diversification in this area remain unclear. Here, Toussaint et al. show that the radiation of the diving beetles Exocelina,originated in emerging highlands of central New Guinea, from which other areas were recently colonized.

Although termites are major human pests, they have an important role in maintaining ecosystem function and biodiversity. Here, the authors sequence the genome and transcriptomes of a dampwood termite and highlight genes that may be involved in the mechanisms underlying insect social behaviour.

This study presents results from a SARS-CoV-2 genomic surveillance study at a university campus in which ~2,000 samples were sequenced over five months. The authors document the replacement of Delta with Omicron as the dominant variant, and describe clinical characteristics and transmission dynamics.

Data sharing is recognized as a way to promote scientific collaboration and reproducibility, but some are concerned over whether research based on shared data can achieve high impact. Here, the authors show that neuroimaging papers using shared data are no less likely to appear in top-ranked journals.

The impact of mercury (Hg) mitigation on microbe-mediated greenhouse gas (GHG) dynamics remains elusive. In this Perspective, the authors fill this gap by synthesizing fragmented evidence on the Hg-microbe-GHG nexus, proposing a roadmap to align Hg mitigation with climate action.

Functional diversity and phylogenetic diversity are expected to be positively correlated. Here the authors show that the covariation between these metrics in vascular plant communities around the world is often either inconsistent or negative.

Since publication of the first issue of Nature Reviews Nephrology 20 years ago, advances across various subspecialities of nephrology have provided insights into disease processes and led to the development of new therapeutics for people with kidney disease. However, despite this progress, many kidney diseases remain untreatable, the costs of kidney disease care are immense, and vast inequities persist in disease burden and access to care. In this Viewpoint, we ask experts from several key subspecialties of nephrology to reflect on progress made over the past 20 years, remaining challenges and the steps needed to move the field forward.

Despite advances in science and technology, persistent challenges in the delivery of healthcare call for care model transformations that have yet to be realized. Artificial intelligence could drive these transformations, but has yet to do so at scale. We present a four-layer framework for leveraging AI to design new care models: Knowledge (clinical content and institutional expertise), Intelligence (AI-powered synthesis and reasoning), Application (user interfaces), and Workflow (redesigned care processes). These layers are modular yet tightly interdependent, requiring cross-functional teams to design across the full stack. We illustrate this framework through an AI-enabled specialty consultation service deployed within Stanford Health Care, a quaternary academic medical center, that integrates all four layers to transform how expertise is delivered. This framework offers health system leaders a roadmap for moving beyond technology deployment toward systematic care model engineering—an organizational capability that will help shape the future of healthcare delivery.

A universal strategy is reported for formation of very low concentration of perovskite precursor inks that yields high-efficiency photovoltaics while substantially reducing toxic waste generation, fabrication cost and process complexity, thus taking a step closer towards commercialization.

Acute oedema after traumatic brain injury is accompanied by the suppression of glymphatic and lymphatic fluid flow due to excessive systemic release of noradrenaline.

Overexpression of complement C4A is associated with schizophrenia risk. Using a novel mouse model, Yilmaz et al. find that increased expression of C4A leads to abnormal synaptic pruning and behavior, suggesting its importance as a therapeutic target.

Ocean alkalinity enhancement (OAE) is seen as a promising method for CO₂ removal as it alters the surface carbon equilibrium, driving the transfer of CO₂ into the ocean. Here the authors computationally map the spatiotemporal efficiency of OAE to identify locations and timing for optimal OAE deployment.

The authors investigate temperature and pH effects on fitness of an abundant marine crustacean (copepod) across 25 generations. Reduced fitness under combined warming and acidification was recovered rapidly, but incompletely, due to interactions between warming and acidification effects.

Using data from MASH clinical trials, an AI model shows comparable performance with respect to individual pathologists in assessing histologic scoring for enrollment criteria and endpoint evaluation

Via its receptor LRP5, Wnt3a stimulates axonal growth in retinal ganglion neurons. Phosphorylation of co-receptor RGMb by VLK induces LRP5 internalization to limit Wnt3a signaling and reduce axon growth.

The restart of collapsed replication forks is associated with high rates of genomic rearrangement. Here, the authors show that during restart initiation rearrangements are driven mainly by Rad51, whereas during elongation they rely more on Rad52.

Ecologists often leverage patterns observed across spatial climate gradients to predict the impacts of climate change (space-for-time substitution). We highlight evidence that this can be misleading not just in the magnitude but in the direction of effects, explain why, and make suggestions for improving the reliability of ecological forecasts.

Several persistent challenges limit the efficacy and applicability of adoptive T cell therapies for cancer, including suboptimal function and/or persistence in vivo, a narrow range of targetable antigens and complex manufacturing processes. This Review discusses the potential of ‘CRISPR 2.0’ precision gene-editing platforms, such as base editing and prime editing to address all of these challenges, and describes the progress made towards clinical translation of these technologies.