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Here, the relationship between unfolding and amyloid aggregation of glaucoma-associated myocilin is probed, showing that myocilin is not at equilibrium and pathogenic aggregation competes directly with unfolding.

Antibodies can have synergistic effects, but mechanisms are not well understood. Here, Ragotte et al. identify three antibodies that bind neighbouring epitopes on CyRPA, a malaria vaccine candidate, and show that lateral interactions between the antibodies slow dissociation and inhibit parasite growth synergistically.

Structural studies show how the PfRCR complex of Plasmodium falciparum forms a bridge between erythrocyte and parasite membranes, and how PfCyRPA-binding antibodies neutralize invasion through a steric mechanism, opening the way to new approaches in rational vaccine design.

The existence of phosphatases specialized in regulating the axon initial segment (AIS) was unclear. Here, the authors show that a PP2A-B55 subunit is selectively enriched at the AIS and contributes to its local phospho-regulation.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Pan-cistrome of the maize leaf under well-watered and drought conditions profiled by haplotype-specific MOA-seq highlights the relevance of transcription factor binding QTLs for understanding phenotypic diversity in maize.

The identification of distinct pyrite-marcasite rosettes in the Doushantuo Formation, South China using microscopy and stable isotope analysis, suggests frequent oxygenation events on the early Ediacaran continental shelves during the emergence of complex life.

Greater trunk flexibility in humans is thought to be a major adaptation to bipedal walking compared to chimpanzees. Here Thompson et al. show that chimpanzees are capable of human-like trunk rotations during bipedalism, suggesting bipedal proficiency was present in early hominins.

Lin, Geng and colleagues identify a non-canonical AHR pathway that is activated by canonical AHR inhibitors, promoting the proliferation of quiescent endothelial cells with potential applications in cell therapy.

The archaeological site Shinfa-Metema 1 in the lowlands of northwest Ethiopia provides early evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

Whole-genome sequence data for 108 individuals representing 28 language groups across Australia and five language groups for Papua New Guinea suggests that Aboriginal Australians and Papuans diverged from Eurasian populations approximately 60–100 thousand years ago, following a single out-of-Africa dispersal and subsequent admixture with archaic populations.

The molecular mechanisms underlying malignant transformation of the Schwann lineage in Schwann cell tumours remain to be explored. Here, the authors suggest that NF2 inactivation leads to PAK activation leading to NF1-mutant Schwann cell tumour de-differentiation and resistance to selumetinib.

Demyelination leads to nerve damage and inflammation. Here, the authors show multisensory gamma stimulation’s potential to mitigate demyelination and neuroinflammation, suggesting that this might be a therapeutic strategy for demyelinating diseases.

BEAN is a Bayesian approach for analyzing base editing screens with improved effect size quantification and variant classification. Applied to low-density lipoprotein (LDL)-associated common variants and saturation base editing of LDLR, BEAN identifies new LDL uptake genes and offers insights into variant structure–pathogenicity mechanisms.

Excavation in Island New Guinea reveals features associated with the Pacific Lapita cultural complex as well as sustained local cultural traditions from 3,480–3,060 years ago, contemporary with the earliest known Lapita settlements 700 km away. This supports New Guinea as a springboard for Lapita dispersal throughout the Pacific and illuminates their origins.

A wireless, minimally invasive emergency rescue device is developed for the active burst-release of stable particulate forms of peptide and hormone drugs into subcutaneous sites in mice.

Vertebral osteoblasts in mouse and human are formed from a precursor skeletal stem cell population that is distinct from long bone skeletal stem cells in function, location and transcriptional programme.

Wireless miniaturized implantable temperature sensors enable real-time monitoring of the progression of inflammatory bowel diseases, as shown in a mouse model of Crohn’s-disease-like ileitis.

An X-ray structure and electrophysiological analysis of mammalian G-protein-gated inward rectifier potassium channel GIRK2 in complex with βγ reveals a pre-open channel structure consistent with channel activation by membrane delimited G-protein subunits.

Perhaps the earliest known signs of life have been found in Quebec, where features such as haematite tubes suggest that filamentous microbes lived around hydrothermal vents at least 3,770 million years ago.

Increasing expression of the autism-associated gene Ube3a, either alone or in combination with seizures, not only impairs sociability in mice but also reduces expression of the synaptic organizer Cbln1 in the ventral tegmental area, thus weakening glutamatergic transmission.

Opsins are responsible for light perception across the animal kingdom. Here the authors show cryo-EM structures of an activated bistable opsin, shedding light on the activation mechanism of this class of bidirectional photoswitches.

If erythrocyte invasion is blocked during the blood stage of infection by Plasmodium parasites, malaria can be prevented. In this Review, structural insights on erythrocyte invasion by the merozoite form of Plasmodium are discussed in the context of rational design of a blood-stage malaria vaccine.

Six surveys show substantial public agreement with misinformation about wind farms. Agreement with diverse contrarian claims is best predicted by participants’ worldviews, most notably the tendency to believe conspiracy theories.

Analysis of the conidial surface proteome of the fungal pathogen Aspergillus fumigatus and three closely related species reveals factors important for evasion and modulation of host immunity

Direct dates for human remains found in association with Initial Upper Palaeolithic artefacts at Bacho Kiro Cave (Bulgaria) demonstrate the presence of Homo sapiens in the mid-latitudes of Europe before 45 thousand years ago.

Comparing infection routes and subsequent transmission of MPXV in the multimammate rat (Mastomys natalensis) indicates increased susceptibility, shedding and transmission via the genital mucosae.

Single-cell transcriptomics studies on human and mouse non-small cell lung cancer and conditional knockout mouse models show that IL-4 from bone marrow basophils drives the development of granulocyte-monocyte progenitors to myeloid cells that suppress antitumour immunity.

Post-fast refeeding increases intestinal stem cell function and tumour formation by augmenting protein synthesis via polyamine metabolism.

An integrated network of chaperones and protein degradation machineries called the proteostasis network (PN) is required to maintain protein homeostasis. Here the authors show that one of the components of the PN, the chaperonin TRiC, interacts with the core transcription-coupled nucleotide excision repair protein CSA to ensure its assembly into the CRLCSA complex.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

Although continuous monitoring of tissue oxygenation is critically important after tissue/organ graft procedures, current technologies have key limitations. Here, the authors develop a miniaturized, minimally invasive, self-anchoring optical probe and demonstrate continuous monitoring of oxygenation in porcine flap and organ models.

Gas exchange for photosynthesis occurs via stomata on the leaf surface and the airspace in the underlying mesophyll tissue. Here, the authors show that stomatal function modulates mesophyll airspace formation and that their coordinated development influences water use efficiency in crops

During innate immune responses, plant cells secrete proteases into apoplastic spaces where they contribute to pathogen resistance. Here Wang et al. show that the Arabidopsis SAP1 and SAP2 proteases cleave the bacterial MucD protein to inhibit growth of Pseudomonas syringae.

The calvarial stem cell niche is populated by a cathepsin K-expressing cell lineage and a newly identified discoidin domain-containing receptor 2-expressing lineage, both of which are required for proper calvarial mineralization.

Dendritic cells (DC) present tumour antigens to T cells but this process is defective in the tumour microenvironment. Here the authors find that downregulation of cholesterol 25-hydroxylase underlies defective cross presentation of tumour antigens.

Pneumococci can alternate between harmless and highly virulent forms. Here the authors show that such variation may be due to random rearrangements in a genetic locus encoding a restriction-modification system, resulting in epigenetic changes that affect expression of many genes.

After injury to the nervous system, many neurons fail to initiate transcriptional programs needed for axon growth. Here the authors examine co-operative binding of factors to regulatory DNA to predict combinations that improve axon growth when ectopically co-expressed.

The maintenance of T resident memory (T_RM) cells within pulmonary tissues is incompletely understood. Here the authors show that antigen presentation by lung epithelial cells maintains function and phenotype of pulmonary T_RM cells within specific locational niches.

The clinical efficacy of standard therapy in lung cancer is limited by high level of heterogeneity. Here, the authors report patient-derived lung cancer organoids from different histological subtypes and show them to faithfully recapitulate the histology, genomics, and drug responses of the primary lung tumours.

An injury-dependent enhancer element is identified that activates gene expression in regenerating zebrafish tissues and can be engineered into DNA constructs that increase tissue regenerative capacity; the element is also active in injured mouse tissue.

Broadly reactive antibodies that recognize influenza A virus HA can be protective, but the mechanism is not completely understood. Here, He et al. show that the inflammatory response and phagocytosis mediated by the interaction between protective antibodies and macrophages are essential for protection.

Basal-like breast cancer is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. Here the authors provide evidence that ID4 is a key controller of mammary stem/progenitor cell self-renewal, acting upstream of Notch signalling to repress luminal fate commitment.

Under extreme conditions, nonlinear lattice dynamics in a material can manifest and reveal unexpected properties. Here, using inelastic neutron scattering and first-principles calculations the authors find the presence of nonlinear travelling waves in a fluorite structured system, which exhibit characteristics different from regular phonons.

A periosteal stem cell specialized in intramembranous bone formation has been identified and was found to be essential for normal bone development and fracture healing.

Visual anemometry measures winds using observations of associated environmental flow–structure interactions such as swaying trees and flapping flags. This Perspective article outlines opportunities for physics and data science to further develop visual anemometry for renewable energy, urban sustainability and environmental science.

Samuli Ripatti and colleagues report the results of a genome-wide association study for circulating lipid levels based on 1000 Genomes Project imputation. Their results implicate several new loci, refine the association signals at many established loci and highlight the impact of low-frequency variants on lipid traits.

A clinical decision support system for diagnosis of myocardial infarction, based on machine learning models that use a single measurement of high-sensitivity troponin, outperforms clinical guidelines that use fixed cardiac troponin thresholds for diagnosis.