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If CO₂ emissions after 2015 do not exceed 200 GtC, climate warming after 2015 will fall below 0.6 °C in 66% of CMIP5 models, according to an analysis based on combining a simple climate–carbon-cycle model with estimated ranges for key climate system properties.

Although novel topological quasiparticles have recently been evidenced, their electrical transport properties remain elusive. Here, the authors report ultra-low resistivity down to 6 nΩcm at 2 K in MoP with a large mean free path, which hints on the exotic properties of triple point fermions.

Over the past 25 years, biophysical technologies such as X-ray crystallography and nuclear magnetic resonance spectroscopy have become key components of drug discovery platforms in many pharmaceutical companies and academic laboratories. This article provides a framework to understand this evolution by describing the key biophysical methods, the information they can provide and the ways they can be applied at different stages of the drug discovery process.

This Review focuses on several recent promising innovations in the field of dye-sensitized solar cells. The key strategies for device engineering and dye design are illustrated, together with explanations as to how these factors affect the robustness and power conversion efficiency of the final device. The outlook towards the commercialization of dye-sensitized solar cells is also described.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Eisosomes are essential for plasma membrane organization in yeast. Structural, biochemical and cell biological studies now reveal that the main eisosome components are part of the conserved BAR-domain family of proteins, which bind and shape membranes.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Branden Moriarity, David Largaespada and colleagues report a Sleeping Beauty forward genetic screen in mice that identifies candidate genes and pathways for osteosarcoma tumor development and progression. They identify sites specifically associated with tumorigenesis and metastasis and find that several candidate oncogenes are involved in axon guidance.

Covalent inhibitors are a successful class of drugs, however, the optimization of targeted covalent inhibitors has challenges due to the need to increase non-covalent interactions and modulate reactivity. Here, the authors study the structure-reactivity-activity relationships of analogues of the EGFR inhibitor poziotinib, showing practical methods to characterize structure-activity relationships, providing insights into the origins of potency and highlighting the effect of chirality on covalent binding.

Leukocyte migration over two-dimensional surfaces is dependent on the integrin family of adhesion receptors, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In this study, all integrin heterodimers from mouse leukocytes were ablated and it is shown that integrins are not required for migration in 3D environments, in vitro and in vivo. Such non-adhesive migration renders leukocytes autonomous from the tissue environment.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Steinberg and colleagues show that long-chain fatty acyl-CoA esters are endogenous ligands for the drug-binding domain of AMPK β1–containing isoforms, and that such binding is critical for enhancement of fatty acid oxidation. These data may help explain how AMPK integrates responses to ketogenic diets, fasting or endurance exercise across distinct tissues in the absence of changes in adenine nucleotides.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

Mechanobiology describes how biological systems respond to mechanical stimuli. This Review surveys basic principles, advantages and limitations of applying and combining atomic force microscopy-based modalities with complementary techniques to characterize the morphology, mechanical properties and functional response of complex biological systems to mechanical cues.

In mice performing an operant task, increases in neural activity in direct- and indirect-pathway spiny projection neurons (SPNs) are associated with action initiation but not with inactivity, and concurrent activation of SPNs from both pathways in one hemisphere precedes the initiation of contraversive movements.

γδ T cells are generally understood to be innate lymphocytes. Prinz and colleagues show that human γδ T cells reconstituted after bone-marrow transplantation have a distinct repertoire that can be shaped by infection with cytomegalovirus, which suggests features of adaptive immunity.

Conformation-specific antibodies capable of monitoring the activation state of a G-protein-coupled seven-transmembrane receptor, the β₂-adrenoceptor, reveals receptor and G-protein activation not only in the plasma membrane, but also in the endosome.

Membrane deformation is necessary to generate endocytic vesicles, but the molecular mechanisms proposed to drive membrane bending are controversial. Stachowiak and Schmid et al. report that crowding of proteins at the membrane is sufficient to induce curvature in vitro.

Male gametocytes rely on mitochondrial ATP to fuel gametogenesis in Plasmodium falciparum.

A DNA origami nanoparticle-based vaccine against SARS-Cov-2 co-delivers viral RBD antigen and CpG adjuvant and elicits a robust protective immunity against the virus in a mouse model.

Fluorescence intensity fluctuation spectrometry provides a rapid and accurate measurement of the identity, abundance and stability of protein oligomers.

Results are presented from the first Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment, a community-based blind test to determine the state of the art in predicting intrinsically disordered regions in proteins.

This Review describes some of the latest techniques that are being used to discover modulators of protein–protein interactions and how current drug discovery approaches have been adapted to successfully target these interfaces.

Good–bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.

By sending few-microjoule single-cycle terahertz pulses to a segmented terahertz electron accelerator and manipulator, 70 MV m^–1 peak acceleration fields, 2 kT m^–1 focusing gradients, 140 µrad fs^–1 streaking gradient and bunch compression to 100 fs are achieved.

Yuan and colleagues developed an artificial intelligence-based method to derive growth patterns and morphological features from hematoxylin and eosin-stained slides of lung adenocarcinoma samples, for improved tumor grading and patient prognostication.

Transcription of eukaryotic protein-coding genes is initiated by RNA polymerase II (Pol II) in a complex with transcription factors including the transcription factor IIB (B). The crystal structure of the complete Pol II–B complex is now presented with complementary functional data. The results shed light on the mechanism of transcription initiation, including the transition to RNA elongation.

Micaela Consens et al. discuss and review the recent rise of transformer-based and large language models in genomics. They also highlight promising directions for genome language models beyond the transformer architecture.

Reputational concerns reinforce the instinct to cooperate in social situations. McAuliffe et al. find that cooperative habits can be overturned in one-shot anonymous interactions, when people learn that defection will not damage their self-interest.

Rumen microbiome biology gets a boost with the release of 410 high-quality reference genomes from the Hungate1000 project.