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Society & CultureOctober 20, 2026

Ancient DNA challenges to admixture narratives: Insights from Notre-Dame Cemetery (1683-1796) in Colonial Montreal, Canada.

Historical narratives of early colonization in Quebec frequently portray French-Indigenous relations as cooperative and characterized by admixture; which are often mobilized in modern debates on false-indigeneity. These narratives have been studied through genealogical, genetic, and bioarchaeological analyses, yet individuals of African descent remain mostly absent from them, while Indigenous peoples are framed largely in relation to colonists. Notre-Dame Cemetery (1683-1796) in Tiohtià:ke-

Health & MedicineOctober 20, 2026

Chronic cigarette smoke exposure induces distinct stem cell states driving genetic driver-specific non-small cell lung cancer subtypes.

Cigarette smoke-induced chronic inflammation (CI) potentiates development of non-small cell lung cancer (NSCLC) by mediating genetic and epigenetic events. Using normal lung organoids (LOs), we define how chronic cigarette smoke condensate (CSC) exposure drives two separate stem cell populations to evolve premalignant states harboring progressive epigenetic and linked transcriptomic abnormalities in the absence of major driver mutations. These dynamics facilitate evolution of an immune evasive s

EnvironmentOctober 20, 2026

Maternal ranging strategies facilitate offspring social play at energetic cost in the most solitary ape.

In most vertebrates, social play among peers is considered essential for behavioral development. Yet in solitary species bearing single offspring, opportunities for social play are inherently scarce. Whether mothers of such species actively facilitate play opportunities for their offspring, and at what cost, remains unknown. We used 15 y of behavioral and movement data (∼32,600 observation hours) from 31 wild Bornean orangutan ( Pongo pygmaeus wurmbii ) mother-offspring pairs to test whet

Physical/TechOctober 20, 2026

Reaction-based cryo-EM resolves the continuous conformational spectrum of CTP synthase catalysis.

Capturing enzymes under native turnover conditions remains a grand challenge in structural biology. Here, we develop a reaction-based cryo-electron microscopy (cryo-EM) strategy that directly samples Drosophila melanogaster cytidine triphosphate synthase (CTPS) from actively catalyzing mixtures containing only natural substrates and allosteric effectors. By integrating reaction-based sampling with three-dimensional variability analysis, we resolve a continuous conformational spectrum of CTPS dur

Physical/TechOctober 20, 2026

GTP orchestrates CTP synthase via an allosteric effector-cycling mechanism.

Cytidine triphosphate (CTP), a fundamental building block of RNA, plays vital roles in diverse biological processes. CTP synthase (CTPS) is the only known enzyme for de novo synthesis of CTP. Efficient CTPS catalysis requires guanosine triphosphate (GTP) in a dose-dependent, nonconsumptive manner; however, the precise mechanism by which GTP drives CTP formation remains unclear. Here, we integrate a series of cryo-EM structures of Drosophila melanogaster CTPS captured from actively catalyzing sam

Society & CultureOctober 20, 2026

Understanding consciousness (biological and artificial) as a society of self-schemas.

This article argues that human cognition is more than the performance of functions such as memory, decision-making, and attention. The brain also builds schematic models of those cognitive functions and uses those models to monitor, predict, and partially control them. When you introspect, your understanding of who you are and what is happening inside of you is derived from those schematic, sometimes inaccurate, but generally useful models, rather than from the actual cognitive functions that ar

EnvironmentOctober 13, 2026

Continuous UV irradiation played an inconclusive role in selecting the canonical genetic alphabet.

An abundance of heterocyclic molecules analogous to canonical nucleobases (i.e., adenine, thymine, guanine, cytosine, and uracil) used as the genetic alphabet in DNA and RNA could have been present in various prebiotic environments on early Earth. However, extant biology generally uses the canonical nucleobases and nucleosides as the genetic alphabet, and not any number of possible noncanonical counterparts. Ultraviolet (UV) irradiation was likely abundant on the surface of the early Earth and h

EnvironmentOctober 13, 2026

Fault-controlled natural hydrogen reservoirs as underground hydrogen storage sites.

Underground hydrogen storage requires geological formations with demonstrated hydrogen containment, yet no conventional storage candidate (salt caverns, aquifers, or depleted hydrocarbon reservoirs) offers direct, prior evidence of H 2 -specific sealing. We propose that subcommercial natural hydrogen reservoirs, where H 2 has accumulated over geological timescales, can serve as precertified storage sites. This proposition is evaluated using the Bulqizë fault-controlled natural H 2 reservoir

Artificial IntelligenceOctober 13, 2026

Deep learning of fossil pollen morphology reveals 25,000 y of ecological change in eastern African grasslands.

Grass (Poaceae) pollen is largely overlooked in investigations of grassland evolution because the pollen of most species cannot be differentiated using traditional optical microscopy. However, the combination of superresolution microscopy and deep learning enables the capture and quantification of distinct morphological variation across the pollen of grass species. Using a semisupervised deep-learning strategy, we trained convolutional neural networks (CNNs) on superresolution images of known mo

Physical/TechOctober 13, 2026

Convergent innovation of (crypto)vivipary via asymmetric dismantling of seed desiccation and dormancy machinery.

Cryptovivipary and vivipary, referred to as (crypto)vivipary, occur across multiple angiosperm lineages and enable embryos to continue developing before dispersal. Yet, this trait raises a fundamental question: how are seed-specific abscisic acid (ABA) responses modulated to support continuous embryonic growth without compromising ABA-dependent vegetative stress tolerance? Here, integrating phylogenomic analyses of independently evolved (crypto)viviparous lineages with spatiotemporal transcripto

Physical/TechOctober 13, 2026

The Benjamini-Hochberg procedure can fail to control the FDR for correlated two-sided Gaussian tests.

The Benjamini-Hochberg (BH) procedure is the standard method for controlling the false discovery rate (FDR) in large-scale studies involving testing multiple hypotheses. Whether the BH procedure controls the FDR for every correlation structure among two-sided Gaussian tests has been a long-standing question, and a positive answer has been believed. Here, we settle the question negatively, by providing examples of Gaussian factor models for which the BH method fails to control the FDR at the nomi

Health & MedicineOctober 13, 2026

Extended fractional Hofstadter states at high field in twisted bilayer graphene above the magic angle.

When a Chern band is partially filled, a fractional Chern insulator (FCI)-the lattice analog of a fractional quantum Hall state-can arise. Though the full range of possible scenarios for producing such a state is not established, the most tractable models combine strong electronic interactions with the quantum geometry of the parent Chern band meeting specific criteria. In twisted bilayer graphene, the importance of interactions can be tuned by varying the interlayer twist. Here, we study a samp

Artificial IntelligenceOctober 13, 2026

Tyrosine phosphorylation unfolds nucleophosmin and disrupts its integration into the nucleolus.

Nucleophosmin (NPM1) is a multifunctional nucleolar protein essential for ribosome biogenesis, genome stability, and stress responses. Its integration into the nucleolus depends on its oligomerization and multivalent interactions that enable liquid-liquid phase separation (LLPS). Here, we investigate how tyrosine phosphorylation at Tyr17, Tyr29, and Tyr67 located within the interface between monomers at the N-terminal oligomerization domain regulates NPM1 structure and function. Replacing tyrosi

Health & MedicineOctober 13, 2026

Phenotypic screening identifies kenpaullone as a prolymphangiogenic compound to improve heart repair following myocardial infarction.

Myocardial infarction (MI) induces cardiac muscle death and its subsequent replacement by a noncontractile fibrotic scar, which underlies progression to heart failure. Current treatments restore blood flow and assist with cardiac workload but do not promote regeneration. We have previously shown endogenous growth of the cardiac lymphatic system following MI and further stimulation with the lymphatic endothelial specific mutated Vascular Endothelial Growth Factor-C (VEGF-C) isoform, VEGFC-C156S,

EnvironmentOctober 13, 2026

Breaking trait scaling via the evolution and regulation of dimorphic decoupling in ants.

The evolution of allometry, changing how morphological traits scale to body size, has fueled adaptive radiations. In ants, allometry has facilitated the repeated evolution of a worker-soldier caste system. Here, we reveal an unexpected morphological pattern and its superorganismal regulation within the hyperdiverse genus Pheidole . We uncovered that antennal sizing between the small worker and the big soldier is identical, lacking intercaste scaling (antennae-body scaling is decoupled) yet retai

Health & MedicineOctober 13, 2026

Dopamine suppresses pathological retinal oscillations and enhances the signal-to-noise ratio.

Infantile nystagmus is a debilitating involuntary eye movement disorder often associated with retinal diseases such as congenital stationary night blindness (CSNB). The oscillating eye movements of infantile nystagmus come with reduced visual acuity and strongly impair quality of life. No cure exists for this condition. Previously, we demonstrated that nystagmus in the CSNB mouse model Nyx nob has a retinal cause. Specifically, we found that synchronized oscillations of retinal ganglion cells (R

Health & MedicineOctober 13, 2026

Spatial and single-nucleus transcriptomics reveals the molecular pathology of type 2 diabetes-associated cognitive dysfunction.

The mechanisms underlying type 2 diabetes-associated cognitive dysfunction (DACD) remain poorly understood, hindering therapeutic progress. Here, we integrated spatial transcriptomics and single-nucleus RNA sequencing to delineate the spatiotemporal molecular and cellular landscape of DACD in brain tissues from 3- and 6-mo-old mouse models. Our findings revealed region- and cell-type-specific transcriptomic alterations, with excitatory neurons in the hippocampus and isocortex emerging as the mos

Physical/TechOctober 13, 2026

NA-CDQuant: Quantitative spectral analysis of nucleic acid structure by circular dichroism spectroscopy.

Understanding the structural conformation and dynamics of nucleic acids in solution is critical for the development of nucleic acid therapeutics involving antisense or mRNA therapies, where controlling stability, efficacy, and manufacturability are important. Circular dichroism (CD) spectroscopy allows rapid and nondestructive solution analysis of the spatial arrangements of nucleic acids. While widely used to analyze protein structure, the potential of CD for DNA- and RNA-based pharmaceutical a

Health & MedicineOctober 13, 2026

53BP1 condensates regulate DNA replication progression and completion.

DNA replication in mammalian cells proceeds in chromosomal domains during defined windows of S phase; however, the mechanisms coordinating replication with restoration of chromatin states remain incompletely understood. Here, we identify p53-binding protein 1 (53BP1) condensates as regulators of heterochromatin replication and epigenetic restoration. Loss of 53BP1 delays mid-to-late S-phase progression, compromises recruitment of epigenetic restoration factors, and impairs timely completion of h

Health & MedicineOctober 13, 2026

Structural basis for membrane-dependent positive feedback regulation of DOCK11 by activated Cdc42.

The guanine nucleotide exchange factor DOCK11 is widely expressed across tissues and activates Cdc42, a Rho family GTPase that regulates cytoskeletal remodeling and cell polarity. Loss-of-function mutations in DOCK11 have recently been linked to inborn errors of immunity. DOCK11 has also been implicated in facilitating hepatitis B virus infection in hepatocytes and has emerged as a potential target for therapeutic interventions. A positive feedback mechanism has been proposed for DOCK11-mediated

EnvironmentOctober 13, 2026

Global grassland productivity and carbon storage benefit from functional diversity under climate change.

Functional diversity plays an important role for ecosystem services of managed grasslands such as their gross primary productivity (GPP) and soil organic carbon (SOC) stocks. Yet vegetation models assessing functional diversity have been limited to small spatial scales. We used the Lund-Potsdam-Jena managed land (LPJmL) competitor stress-tolerant ruderal (CSR) model to assess the role of functional diversity for managed grassland GPP and SOC under climate change at the global scale. LPJmL-CSR si

Health & MedicineOctober 13, 2026

Trans - and cis -interaction dynamics of cadherin complexes on membranes visualized by high-speed atomic force microscopy.

Classical cadherin-mediated cell-cell adhesion is important for maintaining the animal body and defects in adhesion cause severe diseases. The combination of trans - (between cells) and cis - (on the same membrane) interactions of the extracellular domains of cadherins is necessary for cadherin clustering in cell-cell junctions, which is essential for robust tissue formation. However, the solution structure and interaction dynamics of trans / cis -binding cadherin complexes have not been observe

Health & MedicineOctober 13, 2026

Diversity and spatial segregation of TRP channels in the closest relatives of animals.

Sensory systems, built around specialized cell types, are central to how animals perceive and respond to their environments. However, the evolutionary origin of these systems remains unclear. Here, we show that choanoflagellates, the sister group of animals, possess remarkably diverse repertoires of transient receptor potential (TRP) channels, an ancient superfamily of sensory ion channels. Comparative analyses indicate that most major animal TRP channel families predate the origin of animals an

Health & MedicineOctober 13, 2026

Enhancement of hippocampal synaptic AMPA receptor function by the antidepressant tianeptine and by opioid peptides.

Management of major depressive disorder (MDD) with conventional therapeutics that enhance monoaminergic neurotransmission requires prolonged treatment prior to clinical benefit and a substantial proportion of patients show little or no improvement. Identifying alternative molecular targets is required to develop efficacious, rapid acting antidepressants. In this regard, tianeptine, an established but atypical clinical antidepressant, is of interest. Tianeptine does not directly influence monoami

Health & MedicineOctober 13, 2026

The NAC transcription factor SOMBRERO controls auxin gradients for columella root cap maturation and turnover.

The plant root cap consists of continuously renewed cells that collectively protect meristematic stem cells, sense environmental stimuli, and guide root growth direction. Auxin gradients within the root cap are essential for cell turnover, root responses to external cues, and root cap development. However, our understanding of how the auxin gradient is established and maintained remains limited. Here, we show that the root cap-specific NAC transcription factor SOMBRERO (SMB), previously implicat

Society & CultureOctober 13, 2026

Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency.

Myocyte enhancer factor 2C (MEF2C) is a transcription factor critical for brain circuit development and cognitive behavior. The loss of one copy of MEF2C leads to MEF2C haploinsufficiency syndrome (MCHS), a neurodevelopmental disorder characterized by intellectual disability, epilepsy, and behavioral phenotypes associated with autism spectrum disorders. Given that numerous genes are regulated by MEF2C, the neuronal and behavioral deficits in MCHS are complex, and there is currently no effective

Society & CultureOctober 13, 2026

Interventions to mitigate post-infection morbidity: Management insights from simple models.

A variety of pathogens that cause acute disease can also affect their host long after recovery. These post-infection effects lead to elevated costs for individuals and societies, which can be mitigated by large-scale interventions. Here, we examine the management of post-infection morbidity with mathematical models. First, we show that long-term usage of nonpharmaceutical interventions can reduce post-acute burden. Second, to investigate how post-infection effects affect optimal vaccination cove

Physical/TechOctober 13, 2026

How biological synapses self-assemble gradient learning.

Existing models of learning in the brain explain how given circuits learn, but not how biology could assemble those circuits in the first place. To address this gap, we formulate Self-Assembling Learning-the study of how learning systems can emerge from lower-level interactions-and introduce one example mechanism, the Self-Assembling Motif (SAM). SAM is self-assembling at two scales: The motif emerges from initially random connectivity under heterosynaptic plasticity rules, and networks of SAMs,

Physical/TechOctober 13, 2026

A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models.

A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO 2 ) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, "hypoxia-in-a-pill" combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Althoug

Physical/TechOctober 13, 2026

SETDB1 preferentially silences evolutionarily young retroelements.

Transposable elements (TEs) are epigenetically silenced through multiple mechanisms, including heterochromatin formation and DNA methylation. Prior studies have implicated SETDB1 and the Human Silencing Hub (HUSH) complex in heterochromatin formation-based TE repression, but precise characterization of repeat subclass and locus-specific effects for SETDB1 and related mechanisms has been limited by short-read transcriptome mapping. Here, we use long-read RNA sequencing mapped to a telomere-to-tel

Society & CultureOctober 13, 2026

Reproducibility of social science research using aggregate statistics with noise infused for differential privacy.

Privacy-preserving analytics such as differential privacy are designed to allow the analysis of sensitive datasets while protecting individuals' privacy. Their deployment, however, has been controversial. Critics maintain that statistical noise injected to preserve privacy can degrade the quality and feasibility of social science research. We select a benchmark of empirical findings from 93 published social science studies involving regression analyses over aggregate statistics. We evaluate whet

Health & MedicineOctober 13, 2026

Multiple-oxygen isotope constraints on aerobic respiration and gross primary productivity.

Primary production on land and in the surface ocean is a critical component of Earth's carbon and oxygen cycles, controlling the uptake of CO 2 and the release of O 2 to the atmosphere. Quantitative estimates of these O 2 and CO 2 fluxes remain challenging. Of the methods used, the triple-oxygen-isotope analysis of O 2 is considered to provide the most robust in situ estimate of gross productivity. However, this method relies on one key assumption-that the oxygen isotope fractionation of aerobic

Health & MedicineOctober 13, 2026

Dystrophic changes of nigrostriatal axons harboring a SYNJ1 Parkinson's mutation suggest catastrophic failure of endocytic mechanisms.

Synaptojanin 1 is a brain enriched phosphoinositide phosphatase implicated in endocytosis at the synapse. A mutation (R258Q) that selectively impairs its Sac1 phosphatase domain causes early onset familial Parkinsonism. Neurons of mice with this mutation display synaptic vesicle traffic defects across the brain, but selective dystrophic changes in a subset of dopaminergic axons in the dorsolateral striatum. Using correlative light microscopy-FIB-SEM of mutant mouse striata to visualize in 3D the

Health & MedicineOctober 13, 2026

IGF2BP1 in 17q-gain cooperates with MYCN to regulate purine biosynthesis and immunotherapy efficacy in neuroblastoma.

Concurrent chromosomal 17q-gain and MYCN amplification define a subset of neuroblastoma associated with particularly adverse clinical outcomes. However, how these genetic alterations synergize to promote tumor progression and whether their cooperation confers therapeutic vulnerabilities remain elusive. We herein performed a CRISPR-based functional screen targeting 17q-gain genes and identified the RNA m 6 A reader IGF2BP1 as a critical MYCN collaborator to promote aggressive neuroblastomas via a

Physical/TechOctober 13, 2026

Quantum Fisher information and photon statistics from shift current shot noise.

Quantum Fisher information (QFI) sets the ultimate precision of optical phase measurements and can reveal multiphoton entanglement. Yet the photon-number fluctuations that encode this sensitivity are difficult to convert into an electrical signal. We theoretically predict that a photodetector utilizing the shot noise of the quantum-geometric shift current of exciton polaritons can measure photon-number statistics and, for pure states, infer the QFI. By solving the Lindblad equation, we obtain th

Health & MedicineOctober 9, 2026

AI-assisted scoping review of code sharing in clinical prediction model research.

Clinical prediction models are increasingly deployed to support diagnostic and prognostic decisions, making reproducibility essential for assessing their reliability and generalizability. Analytical code supports independent assessment of these processes, yet its availability in the literature remains limited. This scoping review quantifies current practices in sharing analytical code to inform the development of TRIPOD-Code, a reporting guideline for code availability and reproducibility. Here

Health & MedicineOctober 9, 2026

Mapping transcriptional responses to cellular perturbations with RNA fingerprinting.

Single-cell perturbation dictionaries measure how cells respond to genetic and chemical perturbations, creating the opportunity to assign causal interpretations to observational data. We introduce RNA fingerprinting, a statistical framework that maps transcriptional responses from new experiments onto reference perturbation dictionaries. RNA fingerprinting learns perturbation representations, or "fingerprints," from single-cell data, then probabilistically assigns query cells to one or more cand

Physical/TechOctober 8, 2026

Advances in Systemic Treatment of Breast Cancer.

Systemic therapy for breast cancer has evolved rapidly since 2020, driven by the expansion of targeted therapies, antibody-drug conjugates, and immunotherapy across biologic subtypes. The integration of tumor molecular profiling and germline testing has enabled increasingly personalized, biomarker-guided treatment strategies. In hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, cyclin-dependent kinase 4 and 6 inhibitors remain foundational, whereas phos

Health & MedicineOctober 8, 2026

Optogenetic Therapy for Restoring Aspects of Visual Function.

Retinitis pigmentosa is an inherited degenerative retinal disease that can lead to irreversible blindness. Optogenetic therapy has shown potential for restoring visual function at late stages of the disease. In this open-label study, we evaluated the safety of ganglion cell-directed optogenetic therapy in 10 participants with blindness due to advanced retinitis pigmentosa. Each participant received a single intravitreal injection of an adeno-associated viral (AAV) vector encoding the red-shifted

Health & MedicineOctober 8, 2026

Nutritional interventions' impacts on human milk: Three trials in low-resource settings.

Human milk (HM) composition is variable to support changing infant needs and is influenced by maternal diet and health. We harmonized HM data from three randomized trials in Burkina Faso (MISAME-III), Pakistan (Mumta-LW), and Tanzania (ELICIT) within the International Milk Composition (IMiC) Consortium to test how maternal nutrition affects HM composition. Balanced energy-protein (BEP) supplements or nicotinamide given to lactating mothers increased milk B-vitamins, while macronutrients, oligosa