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Oct 15Thu
  1. Cephalalgia41

    Alterations in the interstitial microenvironment across headache phases and clinical phenotypes in migraine: A multimodal diffusion MRI study.

    Multimodal diffusion MRI found no overall differences between migraine participants and healthy controls, but chronic migraine with medication-overuse headache showed reduced extracellular volume fraction and increased intracellular volume fraction versus controls, in the corpus callosum, anterior thalamic radiation, cingulum and optic radiations. Similar alterations appeared during headache. The findings suggest interstitial microenvironment changes tied to headache phase and disease burden rather than a stable trait.

  2. Nature77

    A microexon regulatory code reveals autism-linked genetic variation.

    An expanded map of neuronal microexons, built from extensive transcriptome profiling, adds hundreds of new microexons, including subtype-specific ones and others that trigger nonsense-mediated mRNA decay. A machine-learning sequence code predicts neuronally spliced microexons and identifies regulatory elements around them. Applied to autism, the code pinpoints rare splicing-altering variants, mostly in idiopathic individuals, that associate with autism status and converge on synaptic and other autism-linked genes.

    Why it matters: It links autism-associated genetic variation to a splicing code for neuronal microexons.

  3. Nature73

    Targeted stimulation of motor cortex ensembles drives learned movements.

    Stimulating about 20 layer 2/3 motor cortex neurons whose activity precedes movement onset triggered lever-press-like movements in task-engaged mice and reproduced the learned population activity pattern. Trial-by-trial variability in the evoked activity and movements was predicted by the initial state of M1 before stimulation. Stimulating movement-following neurons, or stimulating in disengaged mice, failed, supporting a causal, active role for M1 in generating learned movements.

    Why it matters: It provides causal evidence that small defined M1 ensembles drive learned movements.

  4. biorxiv.org61

    A microbiota-driven neuroepithelial feed-forward circuit drives gastroesophageal junction tumorigenesis

    Bile acid remodeling enriches the oral commensal Prevotella melaninogenica at the gastroesophageal junction, where bacterial succinate activates vagal sensory neurons and SUCNR1-expressing tuft cells. Tuft cells release 15-d-PGJ2 to sensitize sensory neurons, while neuronal CGRP drives expansion and tuft-cell differentiation of neuro-responsive epithelial progenitors through RAMP1, forming a self-reinforcing microbiota-neuron-epithelium circuit that promotes dysplastic progression. Genetic or pharmacological disruption of the circuit, including with the approved CGRP antagonist rimegepant, suppresses tumor development.

  5. biorxiv.org54

    Transcriptomic and phenotypic characterization of Alzheimer's disease risk genes in neurons and astrocytes highlights shared and cell type specific cellular mechanisms

    Knockouts of roughly 250 candidate Alzheimer's disease genes in iPSC-derived iNeurons and iAstrocytes show highly cell-type-specific effects that converge on shared pathways. Disease-linked expression programs from postmortem patient samples responded to the knockouts, and phenotypic analyses profiled each gene. The screen identified CCDC6 roles in cell cycle and activation state in iAstrocytes and C2orf49 regulation of endoplasmic reticulum stress responses in iNeurons.

  6. nature.com81

    A microexon regulatory code reveals autism-linked genetic variation

    An expanded map of neuronal microexons and a machine learning model of microexon splicing reveal rare human genetic variation predicted to converge on a subset of microexons in genes linked to nervous system biology and neurodevelopmental disorders. Analysing 4,790 bulk RNA-seq samples and 47,380 single nuclei from human cortex, the authors detected 1,514 previously unannotated microexons, 292 of them differentially spliced between neural and non-neural cells. The work points to non-coding variants as a possible contributor to the roughly 85% of autism cases with no identified genetic cause.

    Why it matters: It offers a mechanistic explanation for much of the unexplained genetic aetiology of autism through non-coding microexon variation.

  7. nature.com71

    Targeted stimulation of motor cortex ensembles drives learned movements

    Optogenetic stimulation of motor-cortex neuron ensembles generated learned neural patterns and movements, showing that precisely timed activity in the primary motor cortex can produce skilled motor output. The work demonstrates an active role for primary motor cortex in skilled motor control rather than passive relay of elsewhere-generated commands.

    Why it matters: Causal evidence that timed motor-cortex ensemble activity alone can produce learned movements.

  8. nature.com63

    Elp1 is required for myeloid differentiation and brain repopulation

    A primary cultured haematopoietic stem and progenitor cell platform was used to analyse the molecular mechanisms of brain myeloid differentiation, and identified the elongation factor ELP1 as an important regulator of this process. ELP1 was shown to be required for myeloid differentiation and brain repopulation, pointing to a new molecular control point in the development of brain myeloid cells.

Oct 14Wed
  1. Cell76

    PTPRS mediates invasion of tetanus neurotoxin into the central nervous system.

    The receptor protein tyrosine phosphatase sigma (PTPRS) is the host receptor that carries tetanus neurotoxin into the central nervous system. Pull-down, mass spectrometry and a luciferase-based in vivo transport assay identified PTPRS as the retrograde transport receptor; global or motoneuron-specific PTPRS knockout abolished TeNT entry into the CNS in mice, and a PTPRS-binding-deficient TeNT mutant caused botulism-like flaccid paralysis. The finding exposes a targetable pathway for post-entry intervention and for drug delivery into the CNS.

    Why it matters: Identifies the long-sought host receptor mediating tetanus neurotoxin entry into the CNS.

  2. Cell75

    A high-dimensional population code in the bat motor cortex during natural dexterous flight.

    Motor cortex in freely flying bats uses a high-dimensional, sparse population code rather than wingbeat-dominated activity. Neurons showed mixed selectivity for flight kinematics and millisecond-scale entrainment to wingbeat phase, with successive wingbeats occupying distinct neural states despite bats executing accurate flights via precise individual wingbeat adjustments. This challenges prevailing views of motor cortical dynamics derived from constrained paradigms.

    Why it matters: It overturns expectations that motor cortex during rhythmic movement is dominated by the movement cycle.

  3. JAMA51

    Clinicopathologic Evaluation of Amyloid Clearance in Alzheimer Disease.

    Extensive amyloid clearance after aducanumab tracked with less downstream Alzheimer pathology in a clinicopathologic case report of a man in his 50s with mild cognitive impairment carrying the p.R47H TREM2 variant, who received 30 doses (cumulative 280 mg/kg) over 4.5 years. At autopsy four years after his final dose, brain regions with low residual amyloid, preferentially at gyral crests, showed less tau and slower longitudinal atrophy on MRI (β = -0.50; P < .001), while regions of high amyloid in sulcal depths had tau levels similar to those of untreated controls.

  4. Nat Biotechnol52

    Engrafting human cortical organoids.

    Xenocortication, a transplantation approach described by Kaganovsky and colleagues, integrates human cortical organoids into the mouse brain by grafting human induced pluripotent stem cell-derived cortical organoids into the cortical cavity of neonatal immunodeficient 'apallial' mice, in which most of the neocortex and hippocampus had been genetically depleted. Magnetic resonance imaging showed the grafts grew approximately 4.7-fold between 2 and 3 months after transplantation and accounted for nearly 92% of the combined cortical tissue volume. The approach addresses limited intracranial space and interactions with existing neural circuits that restrict organoid growth and integration after transplantation into rodents.

    Why it matters: Reports a transplantation method that markedly improves growth and integration of human cortical organoids in mice.

Oct 13Tue
  1. nature.com57

    Human–artificial intelligence collaboration for comanaging epilepsy in real time

    A moderated large language model-based chat interface let epilepsy monitoring patients converse with their electroencephalography monitoring in real time via smartphone. In the small study, patient feedback reduced seizure-detector false alarms by about 80% without clinician input. This points to human-AI collaboration as a way to improve seizure detection accuracy in ambulatory monitoring.

Oct 12Mon
  1. Mult Scler41

    Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis.

    Autologous haematopoietic stem cell transplantation was associated with a reduction in paramagnetic rim lesions, a marker of chronic inflammation that disease-modifying therapies barely affect. In 30 transplanted people with multiple sclerosis, PRL count decreased in 40% of PRL-positive cases scanned before and after AHSCT and in 57% of those scanned after only, with no new PRL appearing. Annualised PRL disappearance rates were -0.36 and -0.43, suggesting an effect on central nervous system microglia/macrophages.

  2. Alzheimers Dement42

    The effects of improved access to diabetes medications on risk of Alzheimer's disease and related dementias.

    A dynamic microsimulation using 10 years of data on Americans aged 51 and older with diabetes estimates that increased utilization of GLP1s and SGLT2s by people with diabetes and HbA1c > 7 could avert 76,000-201,000 cases of Alzheimer's disease and related dementias over 10 years. Risk reduction is largest for Black and Hispanic individuals and those with HbA1c > 8, pointing to access and adherence for high-risk groups as the target with the largest benefit.

  3. doi.org50

    Vagal sensing of altered gut microbiota links to externalizing behaviors

    Sirtuin 3 (Sirt3) deficiency in mice produces externalizing, mood-related behaviors together with altered gut microbiome composition, elevated plasma choline, reduced GABA in the nucleus of the solitary tract, and changed expression of synaptic plasticity-related genes in the amygdala and BNST. Subdiaphragmatic vagotomy reversed these measures, making vagotomized Sirt3-knockout mice similar to wild-type mice. The work places the vagus nerve as the conduit linking host genetics, gut microbiota, and behavior.

    Why it matters: It identifies vagal signaling as the mechanistic link between a host gene, gut microbiota, and behavior.

Oct 11Sun
  1. biorxiv.org62

    Spatiotemporal AI modeling of gene regulation and variant effects in the developing human brain

    Seal, an interpretable AI transfer learning framework, models gene expression and variant effects with spatiotemporal resolution across 26 brain regions, 30 cell types, and seven developmental stages of the human brain. Applied to GWAS, it identifies cell types and developmental windows relevant to six neuropsychiatric conditions, and in Simons Simplex Collection autism whole genome data it uncovers a significant burden of de novo regulatory variants in transient fetal excitatory neurons.

    Why it matters: It links disease-associated variants to specific cell types and developmental windows in the developing brain.

  2. biorxiv.org61

    Cellular and molecular census of the pleiotropic disease locus Negr1 in zebrafish

    A knock-in reporter at the zebrafish Negr1 locus, combined with single-cell transcriptomics, whole-brain registration and single-neuron projection mapping, maps where this pleiotropic disease locus acts. Negr1 expression is graded across neuronal classes of brain and retina, radial glia, astrocyte-like cells and, most consistently, oligodendrocyte progenitor cells, with projection mapping suggesting three conserved hubs: olfactory bulb projection neurons, tectal periventricular projection neurons and cerebellar eurydendroid cells. The results support dose perturbation of a broadly expressed gene as the source of Negr1 pleiotropy across BMI, major depression, schizophrenia, autism-spectrum conditions and anorexia.

    Why it matters: It gives a cell-type atlas for a locus tied to BMI, depression, schizophrenia, autism and anorexia, informing which cells each trait may arise from.

Oct 10Sat
  1. Sci Adv77

    Insights into temporal and spatial dynamics of short association fiber formation in the human fetal brain.

    In utero diffusion MRI and histology reconstruct short association fiber development in 243 fetuses, showing SAFs emerge before sulcal folding as flat, loosely arranged pathways along the subplate-white matter interface and later reorganize into U-shaped bundles. Maturation follows a sensorimotor-to-association gradient with nonlinear, bundle-specific trajectories, subplate changes preceding axonal coherence gains and early myelination. The work maps how the brain's local wiring forms prenatally and the origins of individual variability.

    Why it matters: It supplies the first in utero timeline of short association fiber formation across 243 fetuses.

Oct 9Fri
  1. biorxiv.org50

    Fine-tuning genomic models on rare splicing events identifies a novel biomarker of TDP-43 pathology

    Fine-tuned OpenSpliceAI, a specialized splice site prediction model, outperformed a splicing head on AlphaGenome's frozen backbone for detecting TDP-43 cryptic exons, though fine-tuning all AlphaGenome weights enabled generalization to held-out data. Genome-wide application of fine-tuned OpenSpliceAI identified new cryptic splicing events in CLDN11 and ARHGAP23, validated in FTLD-TDP brain tissue. The CLDN11 cryptic exon is predicted to generate a neoepitope that could serve as an oligodendrocyte-specific biomarker of TDP-43 pathology.

  2. Nature75

    A split attractor design for rapidly writing a navigational goal.

    Disinhibition acts as a gate that rapidly writes a heading measurement into a recurrent memory circuit in the fly navigation centre. Whole-cell recordings and modelling show that h∆K and PFG neurons form a ring attractor whose persistent bump activity depends on recurrent excitation, with inhibition decoupling h∆K from PFG during turns and rest. Inhibitory input onto h∆K rises during turns and is suppressed during odour and goal-directed runs, matching the model.

    Why it matters: It identifies a synaptic mechanism for rapid switching of attractor-based working memory circuits.

  3. Sci Adv54

    Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons.

    Rod photoreceptors drive aerobic glycolysis in the retina and need both glycolysis and oxidative phosphorylation to maintain ATP, while inner retinal neurons (RBPMS-positive ganglion and calretinin-positive amacrine cells) rely on oxidative phosphorylation. Two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols also showed rods can metabolize lactate, and a retinitis pigmentosa mutation increased lactate production in rods with otherwise subtle metabolic changes.

Oct 8Thu
  1. biorxiv.org45

    Sex-dependent DNA methylation in amyotrophic lateral sclerosis

    A blood-based epigenome-wide association meta-analysis of 8,946 individuals (5,129 males, 3,817 females) from Project MinE and an Australian cohort identified seven sex-dependent ALS-associated differentially methylated positions at P < 9 × 10-8, mapping to KCNQ1, ADPRH, HLA-F, GHRLOS, IRF5, RAD51B and one intergenic region. Sex-stratified case-control analyses alone found no genome-wide significant sex differences; the interaction model did, with the strongest signal at KCNQ1 (P = 3.1 × 10-9). Six of the seven positions survived a four-stratum sensitivity analysis and none appeared in previous conventional ALS methylation analyses, pointing to a distinct sex-conditional component of the ALS blood methylome.

  2. doi.org60

    Intrinsic circadian organization of the spinal cord and dorsal root ganglia

    The spinal dorsal horn and dorsal root ganglia (DRGs) harbor tissue-autonomous circadian clocks, shown by sustained PER2 oscillations in real-time bioluminescence imaging. RNA sequencing across a 52-hour time course identified 626 rhythmic genes in DRGs (3.6% of expressed genes), arranged in discrete phase clusters enriched for transport, neuronal structure, and proteostasis. The work establishes peripheral sensory tissues as intrinsively circadian and maps their temporal molecular organization.

Oct 7Wed
  1. nature.com68

    A split attractor design for rapidly writing a navigational goal

    A recurrent h∆K–PFG neural circuit produces persistent heading memories using slow excitation, fast inhibition and a disinhibitory gate. Disinhibition acts as the switch that controls functional coupling of the network, allowing rapid transitions between measurement and memory states. The work identifies a circuit mechanism for writing a navigational goal quickly.

    Why it matters: It explains a neural circuit mechanism for rapidly storing a navigational goal.

  2. JAMA70

    Amyloid PET Quantitation and Centiloid Thresholds in the Diagnosis of Alzheimer Disease: An Individual Participant Data Meta-Analysis.

    An individual participant data meta-analysis of 49 227 amyloid PET scans from 53 studies across 15 countries establishes data-driven Centiloid cutoffs for amyloid positivity. Gaussian mixture modeling set a single positivity cutoff of 18 Centiloids, while correspondence with visual reads gave 27 Centiloids (Cohen κ, 0.86); scans between 11 and 26 Centiloids fall in a lower certainty range. These thresholds replace variable cutoffs with standardized bounds for clinical and trial interpretation of amyloid PET.

    Why it matters: It fixes standardized Centiloid positivity thresholds from 49 227 scans, directly affecting eligibility decisions for amyloid-targeting therapies.

  3. Sci Adv55

    Population connective field modeling reveals proto-retinotopic visual cortex organization in the prenatal human brain.

    Proto-retinotopic organization emerges in the visual cortex by the second trimester of pregnancy. Population connective field modeling applied to 871 resting-state fMRI datasets from prenatal to young adult age revealed topographically organized eccentricity and polar angle connectivity maps in V2 and V3 as early as the 21st week of gestation. The maps therefore develop before any visual experience.

Oct 6Tue
  1. Brain59

    Blood-brain barrier opening with focused ultrasound reduces neuromelanin in a non-human primate model.

    Repeated low-intensity focused ultrasound combined with microbubbles (LIFU-MB) reduced neuromelanin accumulation in a non-human primate model overexpressing human tyrosinase. Animals showed Parkinson's-compatible early pathology including extracellular neuromelanin release, iron accumulation, nigral inflammation, and intracellular inclusions without substantial dopaminergic cell loss. LIFU-MB treatment markedly reduced both intracellular and extracellular neuromelanin, with a trend toward decreased free ferric iron, indicating a non-invasive intervention can counteract excessive neuromelanin buildup.

  2. Sci Transl Med66

    Cranial bone marrow-derived monocytes promote neuroinflammation in chronic traumatic brain injury.

    Cranial bone marrow-derived inflammatory monocytes/macrophages migrate into the brain and drive chronic neuroinflammation and neurological deficits after traumatic brain injury, with the effect worsening with age. Age-related PPARα deficiency caused lipid metabolism dysfunction in these cells, promoting inflammatory chromatin states. In a randomized trial of 40 older adult patients with cTBI, fenofibrate reduced plasma neurofilament light chain levels and improved cognitive function.

    Why it matters: It links cranial bone marrow myelopoiesis to chronic neuroinflammation after TBI and shows fenofibrate improved outcomes in a 40-patient trial.

  3. biorxiv.org47

    Conservation of gene co-expression networks and neuropsychiatric-neurological disease gene programs between mouse and human frontal cortex at single-cell resolution

    Co-expression partners of individual genes are only modestly conserved between mouse medial PFC and human dorsolateral PFC: across 13,214 genes and 246,211 single-nucleus RNA-seq profiles, the median partner similarity was 0.169, rising to at most 0.349 after noise correction. Co-expression modules, however, were strongly preserved, and four of five human modules recurred in an independent human dataset. Neuropsychiatric disease genes were no more conserved than matched control genes, and no disease gene showed different partners across species, temperating assumptions of gene-level conservation in mouse models.

  4. Sci Adv59

    Speech clocks decode dementia phenotypes, social exposome, and biological aging.

    A speech clock built from acoustic and linguistic features of 2928 individuals across five Latin American countries estimates chronological age and yields speech age gaps that separate healthy controls from patient groups, ordered HC < AD < nldFTD < ldFTD. The gaps tracked p-Tau217 in AD, social exposome in controls and AD, brain clocks in the FTD groups, and epigenetic age across several clocks. The work positions speech as a scalable, low-cost biomarker candidate for underrepresented settings.

    Why it matters: Speech-based age gaps distinguished four dementia phenotypes and aligned with molecular, brain and social aging markers.

  5. medrxiv.org48

    Resection of highly functionally connected glioma regions predicts long-term cognitive preservation

    Resecting more glioma regions with high functional connectivity (HFC) on preoperative MEG predicted better long-term cognitive outcome rather than worse. In a preregistered analysis of 54 adults with diffuse glioma, resected HFC voxels were associated with less cognitive decline at ~1 year (48% declined; OR 0.85, P = .02) and showed no association with neurological decline at short-term (48% declined; OR 0.98) or long-term follow-up (27% declined; OR 0.99). The finding runs counter to the short-term risk attributed to HFC areas and supports non-invasive MEG connectivity mapping to guide the onco-functional balance in glioma surgery.

Oct 3Sat
  1. Nature67

    Prion-like transmission of human tau strains in the mouse brain.

    Human tau filaments from Alzheimer's disease and corticobasal degeneration brains, injected into wild-type mice, seeded assembly of mouse tau amyloid filaments with the same structures as the seeds. This demonstrates that tau strains retain their structural identity upon transmission, a core tenet of the prion hypothesis not previously shown. The work also establishes the mouse as a model for studying how distinct tau folds drive disease-specific brain pathology.

    Why it matters: It directly demonstrates that tau strains retain structure on transmission, a previously unproven pillar of the prion hypothesis.

  2. nature.com62

    Prozac use for childhood depression skewed by single flawed medical trial

    A single 40-child trial of fluoxetine (Prozac) conducted in Iran and published in 2006 appears to have skewed the evidence base for treating depression in children and adolescents. Re-running the 2016 and 2020 Lancet meta-analyses without that trial, whose implausibly large effect size favored fluoxetine over nortriptyline, made fluoxetine's benefits over placebo disappear. The authors say guideline committees should review their recommendations for fluoxetine in paediatric depression rather than stop prescribing.

    Why it matters: One untrustworthy trial, not new data, explains why major meta-analyses of fluoxetine for paediatric depression disagreed.

Oct 2Fri
  1. Nature66

    Functional role of skull lymphoid structures in CNS immunosurveillance.

    Lymphoid structures with germinal-centre-like formations exist in skull bone marrow, harbouring follicular-helper-like T cells that promote B cell activation and humoral immunity through CD40L, IL-21 and IFNγ signalling. These adaptive immune cells surveil CNS-derived antigens and contribute to anti-tumour immune responses in mouse brain cancer models, identifying skull bone marrow as a site of CNS immunosurveillance.

  2. Nature56

    An amygdala to anterior hypothalamic circuit gates stress sensitivity.

    Prior stress reworks an amygdala-to-anterior hypothalamic nucleus (AHN) circuit that heightens sensitivity to later stressors, whole-brain activity mapping in previously stressed mice shows. AHN activity scales with negative valence, prior stress increases the proportion of valence-sensitive AHN neurons, and inhibiting AHN neurons blunts stress responses while silencing amygdala inputs to the AHN abolishes sensitized stress responses. The work identifies a causal pathway linking adversity to later stress sensitivity.

  3. Nature67

    A cholinergic hub in the nucleus accumbens gates opioid-reward learning.

    Blocking opioid receptors specifically on accumbal cholinergic interneurons abolishes morphine conditioned place preference in mice, even though dopamine increases in the nucleus accumbens are unaltered. The study used naloxoneDART, a cell-type-specific naloxone analogue, which prevented morphine-induced acetylcholine reductions while leaving hyperlocomotion, sensitization and acute analgesia intact. The work identifies a cholinergic gate for opioid-reward learning separable from analgesia.

  4. Nature73

    A two-hit mechanism triggers autoimmune hair loss.

    Autoimmune alopecia can be triggered by a two-hit mechanism: transient regulatory T cell depletion during the anagen phase of the hair cycle causes CD8+ T-cell-mediated destruction of hair follicle stem cells and hair loss, while telogen skin is resistant. Anagen susceptibility depends on sympathetic nerve activity, which drives noradrenaline-ADRB2 signalling, reactivation of endogenous retroviruses, and AIM2-dependent innate immune activation. Genetic ablation of Aim2 or pharmacological inhibition of ERV reverse transcription protects against disease; stress or optogenetic sympathetic activation renders telogen skin susceptible.

    Why it matters: It defines a mechanistic trigger for tissue-specific autoimmunity, linking neural activity, endogenous retroviruses and Treg cells, with druggable entry points.

  5. Nature45

    Spatiotemporal clonal architecture of the newborn mouse forebrain.

    Lentiviral barcoding combined with spatial transcriptomics maps clonal lineages across the newborn mouse forebrain, including cortex, hippocampus, striatum, thalamus and olfactory bulb. The work reveals lineage links between medium spiny neurons, striatal astrocytes and olfactory bulb neurons, and shows GABAergic clones that disperse broadly are enriched for neurodevelopmental disorder genes. It establishes that glutamatergic neurons and astrocytes stay clonally local while GABAergic neurons relate to oligodendrocyte precursors and disperse.

Oct 1Thu
  1. Cell71

    Gut microbiota primes stroke severity via the AHR in intestinal dendritic cells.

    Indole-producing Escherichia coli enrichment is linked to worse ischemic stroke outcomes in mice and patients, working through aryl hydrocarbon receptor (AHR) signaling in intestinal dendritic cells. Dendritic-cell-specific AHR deletion improved stroke outcomes, and pharmacological AHR inhibition promoted gut-derived dendritic cell accumulation in the meninges with increased regulatory T cells and reduced neuroinflammation, protection lost when Tregs were depleted. The work defines a microbiota-AHR axis priming intestinal immunity before brain injury and marks microbial tryptophan metabolism as a therapeutic target.

    Why it matters: Identifies a specific gut-microbe-to-brain mechanism, indole-AHR in dendritic cells, that can be drugged to improve stroke outcome.

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