Biology subjects

Brown, T. T.

Publications and source records attributed to Brown, T. T..

5 recordsLinked to original sources

bioRxiv2023

Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection

People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging-associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.

microbiology↗

bioRxiv2023

Reports of the death of brain-behavior associations have been greatly exaggerated

Magnetic resonance imaging (MRI) is a popular and useful non-invasive method to map patterns of brain structure and function to complex human traits. Recently published observations in multiple large scale studies cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional MRI, which seems to account for little behavioral variability. We leverage baseline data from thousands of children in the Adolescent Brain Cognitive DevelopmentSM (ABCD(R)) Study to inform the replication sample size required with both univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 41 individuals in the replication sample for working memory-related functional MRI, and [~]100 subjects for structural MRI. Even with 100 random re-samplings of 50 subjects in the discovery sample, prediction can be adequately powered with 98 subjects in the replication sample for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many investigators research programs and grants.

neuroscience↗

bioRxiv2022

White matter and literacy: a dynamic system in flux

Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individuals educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to reading skills over development or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N=14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the single-observation datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.

neuroscience↗

bioRxiv2019

Variations in Brain Morphometry Among Healthy Preschoolers Born Very Preterm

BackgroundPreterm birth is associated with an increased risk of neonatal brain injury, which can lead to alterations in brain maturation. Advances in neonatal care have dramatically reduced the incidence of the most significant medical consequences of preterm birth. Relatively healthy preterm infants remain at increased risk for subtle injuries that impact future neurodevelopmental and functioning.\n\nAimsTo investigate the gray matter morphometry measures of cortical thickness, surface area, and sulcal depth in the brain using magnetic resonance imaging at 5 years of age in healthy children born very preterm.\n\nStudy designCohort study\n\nSubjectsParticipants were 52 children born very preterm (VPT; less than 33 weeks gestational age) and 37 children born full term.\n\nOutcome measuresCortical segmentation and calculation of morphometry measures were completed using FreeSurfer version 5.3.0 and compared between groups using voxel-wise, surface-based analyses.\n\nResultsThe VPT group had a significantly thinner cortex in temporal and parietal regions as well as thicker gray matter in the occipital and inferior frontal regions. Reduced surface area was found in the fusiform area in the VPT group. Sulcal depth was also lower in the VPT group within the posterior parietal and inferior temporal regions and greater sulcal depth was found in the middle temporal and medial parietal regions. Results in some of these regions were correlated with gestational age at birth in the VPT group.\n\nConclusionsThe most widespread differences between the VPT and FT groups were found in cortical thickness. These findings may represent a combination of delayed maturation and permanent alterations caused by the perinatal processes associated with very preterm birth.

neuroscience↗

bioRxiv2019

Movement abilities and brain development in preschoolers born very preterm

AimTo examine how healthy preschoolers born very preterm (VPT) with and without significant movement impairments differ from full term (FT) controls in subcortical brain volume measures and white matter diffusion properties.\n\nMethodA case-control, observational study of fifty-four VPT-born and 32 FT-born children were administered the Movement Assessment Battery for Children - Second Edition (MABC-2) and underwent MRI within 6-months of starting kindergarten. Selected subcortical structural volumes, fractional anisotropy (FA), and mean diffusivity (MD) of selected white matter tracts were compared across VPT children with movement impairments (VPT-abnormal), and VPT and FT children without movement impairments.\n\nResultsThe VPT-abnormal group had higher MD in the corpus callosum and inferior frontal-occipital fasciculus and lower FA in the anterior thalamic radiations, corpus callosum, and cingulum than the FT group. The forceps major was particularly affected in the VPT-abnormal group compared with the VPT and FT groups without movement impairments. Both VPT groups had reduced brainstem and cerebellar white matter volumes and larger lateral ventricles compared to the FT group.\n\nInterpretationMovement impairments in healthy VPT preschoolers were associated with more abnormalities in white matter integrity and reduced subcortical brain volumes most likely reflecting a greater extent of white matter damage associated with their very preterm birth.

neuroscience↗