Biology subjects

Baker, F. C.

Publications and source records attributed to Baker, F. C..

5 recordsLinked to original sources

bioRxiv2025

Sleep duration and efficiency moderate the effects of prenatal and childhood ambient pollutant exposure on global white matter microstructural integrity in adolescence

BackgroundAir pollution is a ubiquitous neurotoxicant associated with alterations in structural connectivity. Good habitual sleep may be an important protective lifestyle factor due to its involvement in the brain waste clearance and its bidirectional relationship with immune function. Wearable multisensory devices may provide more objective measures of sleep quantity and quality. We investigated whether sleep duration and efficiency moderated the relationship between prenatal and childhood pollutant exposure and whole-brain white matter microstructural integrity at ages 10-13 years. MethodsWe used multi-shell diffusion-weighted imaging data collected on 3T MRI scanners and objective sleep data collected with Fitbit Charge 2 from the 2-year follow-up visit for 2178 subjects in the Adolescent Brain Cognitive Development Study(R). White matter tracts were identified using a probabilistic atlas. Restriction spectrum imaging was performed to extract restricted normalized isotropic (RNI) and directional (RND) signal fraction parameters for all white matter tracts, then averaged to calculate global measures. Sleep duration was calculated by summing the time spent in each sleep stage; sleep efficiency was calculated by dividing sleep duration by time spent in bed. Using an ensemble-based modeling approach, air pollution concentrations of PM2.5, NO2, and O3 were assigned to each childs residential addresses during the prenatal period (9-month average before birthdate) as well as at ages 9- 10 years. Multi-pollutant linear mixed effects models assessed the associations between global RNI and RND and sleep-by-pollutant interactions, adjusting for appropriate covariates. ResultsSleep duration interacted with childhood NO2 exposure and sleep efficiency interacted with prenatal O3 exposure to affect RND at ages 10-13 years. Longer sleep duration and higher sleep efficiency in the context of higher pollutant exposure was associated with lower RND compared to those with similar pollutant exposure but shorter sleep duration and lower sleep efficiency. ConclusionsLow-level air pollution poses a risk to brain health in youth, and healthy sleep duration and efficiency may increase resilience to its harmful effects on white matter microstructural integrity. Future studies should evaluate the generalizability of these results in more diverse cohorts as well as utilize longitudinal data to understand how sleep may impact brain health trajectories in the context of pollution over time.

neuroscience↗

bioRxiv2023

The Bicaudal-D/Egalitarian complex defines the specificity of cargo transport by Dynein.

Numerous motors of the Kinesin family contribute to plus-end microtubule transport. However, almost all transport towards the minus-end of microtubules involves a single motor, cytoplasmic Dynein (Dynein). To gain motility, Dynein must interact with activating cargo adaptors. One such adaptor is Bicaudal-D (BicD; BICD2 in humans). Mutations in BICD2 are associated with Spinal Muscular Atrophy (SMA), a degenerative motor neuron disease. BicD is autoinhibited from binding Dynein in the absence of cargo. A well-characterized cargo for BicD is the RNA binding protein, Egalitarian (Egl). Egl in conjunction with BicD links mRNA to Dynein in the Drosophila egg chamber and embryo. To better understand how Dynein is activated and whether BicD links additional cargo with Dynein, we defined the BicD interactome in the presence and absence of Egl. This revealed a vast number of potentially novel BicD cargos including the nucleoporin Nup358/RANBP2, a known cargo of mammalian BICD2. In strains depleted of Egl, BicD remained associated with most of its cargo including Nup358. However, the interaction of BicD with Dynein was reduced. Consequently, the localization of Nup358 and its association with Dynein was disrupted. Thus, while BicD can bind diverse cargos, linking these cargos with Dynein requires Egl. Furthermore, our studies revealed that a SMA associated mutation in the cargo binding domain of BicD enhanced the Dynein mediated localization of certain cargos but disrupted the localization of others. At the organismal level, this mutation resulted in compromised mobility. Specific transport defects might therefore underlie the etiology of BicD associated SMA.

cell biology↗

bioRxiv2021

In vivo proximity biotin ligation identifies the interactome of Egalitarian, a Dynein cargo adaptor.

Numerous motors of the Kinesin family contribute to plus-end directed microtubule transport. However, almost all transport towards the minus-end of microtubules involves Dynein. Understanding the mechanism by which Dynein transports this vast diversity of cargo is the focus of intense research. In select cases, adaptors that link a particular cargo with Dynein have been identified. However, the sheer diversity of cargo suggests that additional adaptors must exist. We used the Drosophila egg chamber as a model to address this issue. Within egg chambers, Egalitarian is required for linking mRNA with Dynein. However, in the absence of Egalitarian, Dynein transport into the oocyte is severely compromised. This suggests that additional cargoes might be liked to Dynein in an Egalitarian-dependent manner. We therefore used proximity biotin ligation to define the interactome of Egalitarian. This approach yielded several novel interacting partners, including P body components and proteins that associate with Dynein in mammalian cells. We also devised and validated a nanobody based proximity biotinylation strategy which can be used to define the interactome of any GFP-tagged protein.

cell biology↗

bioRxiv2021

Alcohol Use Disrupts Age-Appropriate Cortical Thinning in Adolescence: A Data Driven Approach

ObjectiveCortical thickness changes dramatically during development and is influenced by adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying heterogeneity from the effects of alcohol. MethodsAdolescents (n=657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) who endorsed little to no alcohol use at baseline were assessed with structural MRI and followed longitudinally at four yearly intervals. Seven unique spatially covarying patterns of cortical thickness were obtained from the baseline scans by applying a novel data-driven method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. ResultsIn most NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts, among moderate drinkers the decline was faster in the younger cohort and slower in the older cohort, among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort (FDR corrected p-values < 0.01). ConclusionsThe NMF method can delineate spatially coordinated patterns of cortical thickness at the vertex level that are unconstrained by anatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers.

neuroscience↗

bioRxiv2018

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.\n\nHighlightsO_LIAn overview of the MRI processing pipeline for the ABCD Study\nC_LIO_LIA discussion on the challenges of large, multisite population studies\nC_LIO_LIA methodological reference for users of publicly shared data from the ABCD Study\nC_LI

neuroscience↗