Biology subjects

Estes, A.

Publications and source records attributed to Estes, A..

5 recordsLinked to original sources

bioRxiv2026

Variation in infant subcortical brain development from 6 to 12 months in Down syndrome

IntroductionDown syndrome (DS), arising from Trisomy 21, is the most common genetic condition associated with intellectual disability. While smaller total brain volumes have been consistently observed in DS, no longitudinal neuroimaging studies have examined volumetric brain development in DS during infancy, a period of rapid neural growth when interventions may have the greatest impact. MethodHigh-resolution T1- and T2-weighted images were acquired during natural sleep in a multisite longitudinal cohort of 44 infants with DS and 39 control infants without DS at ages 6 and 12 months. Neuroimaging data were harmonized to reduce batch effects, and a novel deep-learning, repeated-measures segmentation approach was applied to optimize neuroanatomical segmentations. Total intracranial volume (ICV) and bilateral absolute subcortical volumes (amygdala, caudate, hippocampus, pallidum, putamen, thalamus) were first directly compared in infants with and without DS at 6 and 12 months. Hierarchical linear modeling (HLM) evaluated longitudinal group differences for each structure, accounting for sex, gestational age, and laterality. Subcortical group differences estimated by HLM were also compared to group differences in total ICV. ResultsICV in infants with DS was lower than controls at 6 months (12.6%; p<.001) and 12 months (16.3%; p<.001). Subcortical structures displayed a range of lower volumes (6.9%-13.1%; ps[≤].003) in infants with DS, although the caudate and putamen were exceptions. Caudate volumes were on average lower in DS but not significantly different from controls, while putamen volumes were on average higher in DS but not significantly different from controls, except for the right putamen, which was significantly larger (5.3%; p=.018) at 6 months. In HLM, ICV and all subcortical structures showed slower growth in DS from 6 to 12 months, except for the amygdala and putamen, which displayed similar growth rates to controls. DS-associated reductions in subcortical volumes were similar in magnitude to ICV, although 12-month caudate and 6- and 12-month putamen volumes were enlarged relative to ICV. ConclusionInfants with DS exhibited substantially reduced ICV and widespread reductions in subcortical volumes and growth from 6-12 months. Across a range of volumetric differences, findings were most distinct in the basal ganglia, for which volume reductions were attenuated in the caudate, while the putamen was uniquely enlarged with comparable growth to controls. These observations support early regional specificity in the neural impact of Trisomy 21 and underscore the utility of infant neuroimaging to inform biologically based interventions and clinical trial readiness in DS.

neuroscience↗

bioRxiv2026

Characterization of the SKC mouse strain as a potential model for keratoconus

BackgroundKeratoconus (KC) is a multifactorial disorder with unclear etiology, characterized by localized thinning and a cone-like protrusion of the cornea. The complex etiology of KC exacerbates the lack of an animal model. Previous studies by Tachibana et al. (2002) described an inbred mouse strain (SKC) with a spontaneous, androgen-dependent, cone-like corneal morphology. This study aimed to investigate the corneal phenotypes of SKC mice through an in-depth ophthalmic examination. MethodsMice (n=53) were examined via slit lamp biomicroscopy with fluorescein staining. Spectral-domain optical coherence tomography (SD-OCT) enabled central corneal thickness (CCT) measurement in selected mice (n=26 eyes), and OCT-based pachymetry mapping (n=16 eyes). In vivo corneal confocal microscopy was conducted on eyes to assess cellular morphology (n= 9 eyes). Eyes were collected for histology analysis (n=22). ResultsLesions and epithelial breaks were present in [~]95% of eyes (n=101). Neovascularization, perforation, scarring, and hydrops were seen primarily in males. An opaque, unilateral cone-like morphology was exclusive to males (n=11). Male and female corneas showed no significant difference in CCT, though pachymetry mapping revealed regional thinning patterns in both sexes. Loosened epithelial tight junctions, stromal fibrosis, vascularization, and inflammation of variable severity were identified in both sexes. ConclusionThis study identified previously unreported corneal phenotypes in SKC mice through ophthalmic examination. Unlike previous studies, gross and histological abnormalities were observed in female SKC mice. Our findings suggest a lower penetrance of the cone-like phenotype ([~]20%) than previously reported ([~]33%) and support that the conical phenotype in male mice may be secondary to keratitis.

pathology↗

bioRxiv2026

Visual Cortical Response Variability in Infants at High Familial Likelihood for Autism

Visual processing undergoes rapid development in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a non-invasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-4). VEP components (P1 and N1) were characterized by their amplitude and latency, as well as trial-to-trial variability in these measures. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both time points, with age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both time points was associated with higher cognitive and language scores at 24 months. In contrast, conventional measures of mean P1 latency and amplitude were not associated with developmental outcomes. These findings suggest that temporal variability in early visual responses may index adaptive sensory-circuit flexibility during a period of rapid experience-dependent development. VEP response-timing variability may therefore provide an early mechanistic marker of sensory-circuit organization relevant to later developmental trajectories. Research HighlightsO_LIGreater trial-to-trial variability in visual cortical response timing was associated with higher cognitive and language scores in infants at high familial likelihood for autism. C_LIO_LIConventional average VEP measures were unrelated to outcomes, suggesting temporal variability may more sensitively capture relevant neural-circuit differences in this population. C_LIO_LIGreater variability in early visual responses may reflect adaptive sensory-circuit flexibility during a critical period of neurodevelopment. C_LIO_LIVEP response-timing measures provide an early mechanistic window into sensory-circuit organization and its relation to later developmental trajectories. C_LI

neuroscience↗

bioRxiv2025

Early cell cycle genes in cortical organoid progenitors predict interindividual variability in infant brain growth trajectories

Human induced pluripotent stem cell (iPSC) derived cortical organoids (hCOs) model neurogenesis on an individuals genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from which they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who have undergone longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of cortical hem cells were associated with in vivo cortical growth rates. Cell cycle associated genes expression in early progenitors at the crux of fate decision trajectories were correlated with cortical growth rate from 6-12 months of age, and were enriched in microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types influencing infant cortical surface area expansion.

neuroscience↗

bioRxiv2018

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-affected Corneas

PURPOSEKeratoconus (KC) is the most common corneal ectasia. We aimed to determine the differential expression of coding and long noncoding RNAs (lncRNAs) in human corneas affected with KC.\n\nMETHODS200ng total RNA from the corneas of 10 KC patients and 8 non-KC normal controls was used to prepare sequencing libraries with the SMARTer Stranded RNA-Seq kit after ribosomal RNA depletion. Paired-end 50bp sequences were generated using Illumina HiSeq 2500 Sequencer. Differential analysis was done using TopHat and Cufflinks with a gene file from Ensembl and a lncRNA file from NONCODE. Pathway analysis was performed using WebGestalt. Using the expression level of differentially expressed coding and noncoding RNAs in each sample, we correlated their expression levels in KC and controls separately and identified significantly different correlations in KC against controls followed by visualization using Cytoscape.\n\nRESULTSUsing |fold change| [≥] 2 and a false discovery rate [≤] 0.05, we identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas. Pathway analysis indicated the enrichment of genes involved in extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Our correlation analysis identified 296 pairs of significant KC-specific correlations containing 117 coding genes enriched in functions related with cell migration/motility, extracellular space, cytokine response, and cell adhesion, suggesting the potential functions of these correlated lncRNAs, especially those with multiple pairs of correlations.\n\nCONCLUSIONSOur RNA-Seq based differential expression and correlation analyses have identified many potential KC contributing coding and noncoding RNAs.

genomics↗