Enteroviruses initiate infection at the intestinal epithelium but can spread systemically to cause severe disease. Although both MDA5 and TLR3 have been implicated in enterovirus sensing, the mechanisms by which the intestinal epithelium detects these viruses remain poorly defined. To address this, we infected human intestinal organoids (enteroids) with echovirus 11 (E11) and compared responses […]
Geographic and temporal trends in etiology-specific diarrhea burden among children in low-resource settings
Background: Several large multisite studies have been conducted to describe etiology-specific burden of diarrhea among children in low-resource settings. Here, we combined data across studies to describe geographic and temporal trends in incidence and attributable fractions (AFs) of etiology-specific moderate-to-severe diarrhea (MSD), and to evaluate etiology-specific case fatality ratios (CFRs). Methods: We harmonized case definitions […]
Phylo-Movies: Animating Phylogenetic Trees from Sliding-Window Analyses
Sliding-window phylogenetic analyses of multiple sequence alignments (MSAs) generate sequences of phylogenetic trees that can reveal recombination and other sources of phylogenetic conflict, yet comparing trees across genomic windows remains challenging. Phylo-Movies is a browser-based tool, also available as a standalone desktop application, that decomposes topological differences between consecutive phylogenetic trees into interpretable subtree migrations […]
Global population structure and phase variation of serotype 12F Streptococcus pneumoniae following the introduction of pneumococcal conjugate vaccine
Abstract Background After the global deployment of pneumococcal conjugate vaccines (PCVs), serotype 12F has become the predominant serotype responsible for invasive pneumococcal disease (IPD) worldwide. As PCVs that include serotype 12F are gradually introduced, we aim to characterise the global population structure and genetic diversity of the 12F capsule locus using whole-genome sequencing. Capsule variants […]
Developmental Correlates of Epigenetic and Polygenic Indices of Cognition and Educational Attainment from Birth to Young Adulthood
Large-scale genomic studies have identified biomarkers of adult cognitive functioning and educational attainment, yet the developmental pathways connecting these biomarkers to adult outcomes remain unclear. Drawing on four cohorts, we examined the developmental correlates of an epigenetic index of adult cognitive function ("Epigenetic-g") alongside polygenic indices of cognition and education. Epigenetic-g and polygenic indices were […]
The B. subtilis translesion polymerase Pol Y1 is not strongly recruited to sites of replication upon different types of DNA damage
One challenge to DNA replication is the presence of unrepaired damage on the template strand, which can stall the replication machinery. This stall can be resolved by the translesion synthesis (TLS) pathway, in which specialized translesion polymerases are recruited to copy damaged DNA. Because TLS polymerases are error-prone, their activity is regulated at multiple levels […]
A critical role of epithelial MHCII in initiation of autoimmune tumorigenesis and sustaining premalignancy growth in the stomach
Autoimmunity is emerging as a new etiology for early-onset gastric cancer (GC). However, it remains unclear what molecular pathways drive the initiation and progression of autoimmune tumorigenesis. Given that Major Histocompatibility Complex Class II (MHCII) is the strongest genetic risk factor for many autoimmune diseases, we hypothesized that MHCII-mediated autoantigen presentation drives tumorigenic differentiation of […]
Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury
Extracellular vesicles (EVs) contribute to the damage caused by traumatic brain injury (TBI) and can cross the blood-brain barrier (BBB). We analyzed plasma-derived EVs from human TBI patients to identify factors potentially contributing to TBI pathology. EVs were isolated using membrane affinity (ExoEasy) and size exclusion chromatography (iZone), both yielding CD9(+) and CD63(+) EVs with […]
Branch-specific plasticity explains distal enrichment of retinotopically displaced inputs in visual cortex
Neurons distribute synaptic inputs across their dendritic tree. In layer 2/3 pyramidal cells of primary visual cortex, spines on distal dendrites share somatic orientation preference but have receptive fields displaced in retinotopic space, which supports tuning to visual edges. However, it is not known how synaptic plasticity rules can lead to specialization of tuning properties […]
OncoMORPHIA: An Integrated Web Platform for Interactive 3D Visualization and Functional Annotation of Cancer Mutations
Summary: The rapid accumulation of cancer genomic data across repositories such as ClinVar, cBioPortal, and the TCGA Pan-Cancer Atlas has created an urgent need for integrated tools that allow researchers to explore mutations in their structural and clinical context without requiring specialized bioinformatics expertise. Here we present OncoMORPHIA, a free, browser-based web platform that unifies […]
Several multiple sequence alignment perturbation methods enhance AlphaFold3 sampling of alternative protein states
Protein function often involves multiple conformational states. Several multiple sequence alignment-perturbing strategies, including stochastic subsampling, clustering, and column masking, have been shown to enhance AlphaFold2 (AF2) sampling of alternative protein states. Here, we evaluate these strategies on AlphaFold3 (AF3) and compare their performance with the BioEmu Boltzmann sampling model on 107 proteins with multiple experimentally […]
Decoupled calcium homeostasis and signaling associated with cytoskeletal instability in YWHAG R132C induced pluripotent stem cell-derived cortical neurons
YWHAG Syndrome (Developmental and Epileptic Encephalopathy 56, DEE56) is an ultra- rare childhood epilepsy associated with neurodevelopmental delays, with no therapeutic intervention available. Multiple de novo mutations in the YWHAG gene, encoding for the 14-3-3gamma protein, have been identified as causative for YWHAG Syndrome. 14-3-3gamma interacts with various targets, including major neurodevelopmental signaling proteins such […]