A5052214500- Advanced Neuroimaging Techniques and Applications
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- RNA modifications and cancer
- Glycogen Storage Diseases and Myoclonus
- Fetal and Pediatric Neurological Disorders
- Cancer-related molecular mechanisms research
- Advanced MRI Techniques and Applications
- Bioinformatics and Genomic Networks
- Ferroptosis and cancer prognosis
- Cerebral Palsy and Movement Disorders
- Molecular Biology Techniques and Applications
- Gene expression and cancer classification
- Mental Health and Psychiatry
- Child and Adolescent Health
- Spinal Dysraphism and Malformations
- Ultrasound Imaging and Elastography
- Barrier Structure and Function Studies
- Medical Research and Practices
- RNA and protein synthesis mechanisms
- Neural and Behavioral Psychology Studies
- Cancer-related Molecular Pathways
- Hydrogen Storage and Materials
- Parkinson's Disease and Spinal Disorders
- Sphingolipid Metabolism and Signaling
University of Miami
2016-2025
Indiana University – Purdue University Indianapolis
2015-2024
Databricks (United States)
2024
Sylvester Comprehensive Cancer Center
2016-2023
Indiana University School of Medicine
2020-2023
Duke Medical Center
2010-2020
Clinical Research Institute
2020
University of Kentucky
2020
Duke University
2011-2020
Johns Hopkins University
2020
The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated contribution in CS or (e-Cig) injury. Primary microvascular cells were exposed nicotine, e-Cig solution, condensed vapor (1-20 mM nicotine) nicotine-free solutions. Compared with nicotine-containing extract, free-CS...
Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer's disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that risk alleles are enriched in myeloid-specific epigenomic annotations. Here, show they specifically active enhancers monocytes, macrophages microglia. We integrated GWAS myeloid transcriptomic datasets using...
OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus gray white matter volumes anterior cingulate gyrus superior frontal were computed from contiguous 1.5-mm magnetic resonance images 23 psychotropic drug-naive OCD (seven male 16 female patients) 27 healthy volunteers (12 subjects 15...
<h3>Context</h3> There is increasing evidence that schizophrenia characterized by abnormalities in white matter. <h3>Objective</h3> To investigate the integrity of matter tracts adolescents with schizophrenia. <h3>Design</h3> Cross-sectional, case-control, whole-brain, voxel-based analysis and fiber tractography using diffusion tensor magnetic resonance imaging. <h3>Setting</h3> University research institute. <h3>Participants</h3> Forty-four individuals (age range, 11-18 years), 23...
Mucopolysaccharidosis (MPS) Type I (MPSI) is caused by mutations in the gene encoding lysosomal enzyme, α-L-iduronidase (IDUA), and a majority of patients present with severe neurodegeneration cognitive impairment. Recombinant IDUA does not cross blood-brain barrier (BBB). To enable BBB transport, was re-engineered as an IgG-IDUA fusion protein, valanafusp alpha, where IgG domain targets human insulin receptor to transport enzyme into brain. We report results 52-week clinical trial on safety...
ABSTRACT High-throughput technologies now produce a wide array of omics data, from genomic and transcriptomic profiles to epigenomic proteomic measurements. Integrating these diverse data types can yield deeper insights into the biological mechanisms driving complex traits diseases. Yet, extracting key shared biomarkers multiple layers remains major challenge. We present multivariate random forest (MRF)–based framework enhanced by novel inverse minimal depth (IMD) metric for integrative...
Physical fatigue crucially influences our decisions to partake in effortful action. However, there is a limited understanding of how impacts effort-based decision-making at the level brain and behavior. We use functional magnetic resonance imaging record markers activity while human participants engage uncertain choices for prospective physical effort, before after bouts exertion. Using computational modeling choice behavior we find that fatiguing exertions cause increase their subjective...
Objective Chronic gastro-oesophageal reflux disease, where acidic bile salts (ABS) into the oesophagus, is leading risk factor for oesophageal adenocarcinoma (EAC). We investigated role of ABS in promoting epithelial-mesenchymal transition (EMT) EAC. Design RNA sequencing data and public databases were analysed EMT pathway enrichment patients’ relapse-free survival. Cell models, pL2-IL1β transgenic mice, deidentified EAC derived xenografts (PDXs) tissues used to investigate Results Analysis...
Correlation of Apparent Diffusion Coefficient and Fractional Anisotropy Values in the Developing Infant BrainJames M. Provenzale1 2, Jared Isaacson3, Steven Chen1, Sandra Stinnett4 5 Chunlei Liu1 6Audio Available | Share
The purpose of this study was to test a first hypothesis that fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values continue change in late childhood adolescence second less mature white matter (WM) regions have higher rate than WM are relatively more mature.Eighty-seven healthy children (50 girls, 37 boys; mean age, 11.2 ± 3.6 years; range, 4.2-17.7 years) underwent six-direction diffusion-tensor imaging with 3-T MRI system. Three neuroradiologists independently drew...
The goal of this study was to determine the degree which ex vivo diffusion tensor imaging (DTI) parameters correlate one another in white matter regions on very high resolution MR scans. Specifically, we hypothesized that radial diffusivity (RD) and apparent coefficient (ADC) would more closely than either with fractional anisotropy (FA). We performed post mortem DTI three canine brains a 7 T scanner (TR = 100 ms, NEX 1, gradient amplitude 600 mT/m, b 1492-1,565 s/mm²) generated maps FA, RD,...
Abstract Alcohol use disorder (AUD) is a complex genetic characterized by problems arising from excessive alcohol consumption. Identifying functional variations that contribute to risk for AUD major goal. Alternative splicing of RNA mediates the flow information DNA gene expression and expands proteome diversity. We asked whether alternative could be factor AUD. Herein, we used Mendelian randomization (MR)-based approach identify skipped exons (the predominant event in brain) risk. Genotypes...
<h3>Objective</h3> To characterize the extent of CNS involvement in children with Pompe disease using brain MRI and developmental assessments. <h3>Methods</h3> The study included 14 (ages 6–18 years) infantile (IPD) (n = 12) or late-onset (LOPD) 2) receiving enzyme replacement therapy. White matter (WM) hyperintense foci seen MRIs were systematically quantified Fazekas scale (FS) grading system a novel approach: individual FS scores from 10 anatomical areas summed to yield total score (range...
Objective This study examined the effect of mucopolysaccharidosis (MPS) type 1 on diffusion tensor imaging (DTI) metrics in canine brain. We hypothesized 1) white matter regions MPS brain would show decreased fractional anisotropy (FA) and increased radial diffusivity (RD) compared to same normal brain, 2) FA, RD more closely correlate with myelin density fiber coherence, 3) DTI histological data from could be used accurately predict degree myelination using metrics. Methods performed one...
Alternative splicing alterations can contribute to human disease. The ability of an RNA-binding protein regulate alternative outcomes be modulated by a variety genetic and epigenetic mechanisms. In this study, we use computational framework investigate the roles certain genes, termed modulators, on changing RBPs' effect regulation. A total 1,040,254 modulator-mediated RBP-splicing interactions were identified, including 137 RBPs, 4,309 events 2,905 modulator candidates from TCGA-KIRC RNA...
Purpose The goal of this study was to compare the diffusion tensor imaging (DTI) metrics from an end-stage canine Krabbe brain evaluated by MR ex vivo those a normal dog brain. We hypothesized that white matter would show decreased fractional anisotropy (FA) values and increased apparent coefficient (ADC) radial diffusivity (RD) values. Methods An 11-week-old euthanized after disease progression. removed placed in solution 10% formalin. performed compared images similarly fixed post-mortem....
Influence of Analysis Technique on Measurement Diffusion Tensor Imaging ParametersEfsun Urger1, Michael D. DeBellis2, Steven R. Hooper3, Donald P. Woolley2, Chen1 and James M. Provenzale1, 4Audio Available | Share
Alternative RNA splicing is an important means of genetic control and transcriptome diversity. However, when alternative events are studied independently, coordinated modulated by common factors often not recognized. As a result, the molecular mechanisms how regulators promote or repress splice site recognition in context-dependent manner well understood. The functional coupling between multiple gene regulatory layers suggests that additional epigenetic components. Here, we developed...
Genetic variants can influence the expression of mRNA and protein. regulatory loci such as quantitative trait (eQTLs) protein (pQTLs) exist in several species. However, it remains unclear how human genetic regulate expression. Here, we characterized six mechanistic models for patterns single-nucleotide polymorphisms (SNPs) their actions on post-transcriptional Data from Yoruba HapMap lymphoblastoid cell lines were analyzed to identify cis-eQTLs pQTLs, well protein-specific QTLs (psQTLs). Our...
Purpose The purpose of this study was to investigate a novel tensor shape plot analysis technique diffusion imaging data as means assess microstructural differences in brain tissue. We hypothesized that could distinguish white matter regions with different compositions. Methods Three normal canines were euthanized at seven weeks old. Their brains imaged using identical protocols on 7T small-animal magnetic resonance system. examined two regions, the internal capsule and centrum semiovale,...
Purpose We describe a novel technique for measuring diffusion tensor imaging metrics in the canine brain. hypothesized that standard method region of interest placement could be developed is highly reproducible, with less than 10% difference measurements between raters. Methods Two sets brains (three seven-week-old full-brains and two 17-week-old single hemispheres) were scanned ex-vivo on 7T small-animal magnetic resonance system. Strict criteria then used by raters to independently measure...
Abstract Background While several multigene signatures are available for predicting breast cancer prognosis, particularly in early stage disease, effective molecular indicators needed, especially triple-negative carcinomas, to improve treatments and predict diagnostic outcomes. The objective of this study was identify transcriptional regulatory networks better understand mechanisms giving rise development incorporate information into a model clinical Methods Gene expression profiles from...