Center Event Calendar

Mark McIntosh,'s picture

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II.

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions.
Author: 
Milham MP
Mark McIntosh,'s picture

Methylated <i>cis</i>-regulatory elements mediate KLF4-dependent gene transactivation and cell migration.

Altered DNA methylation status is associated with human diseases and cancer; however, the underlying molecular mechanisms remain elusive. We previously identified many human transcription factors, including Krüppel-like factor 4 (KLF4), as sequence-specific DNA methylation readers that preferentially recognize methylated CpG (mCpG), here we report the biological function of mCpG-dependent gene regulation by KLF4 in glioblastoma cells. We show that KLF4 promotes cell adhesion, migration, and morphological changes, all of which are abolished by R458A mutation.
Author: 
Xia S

Center for Diversity Conference Videos

2017 Center for Diversity in Public Health Leadership Training

Mark McIntosh,'s picture

Whole-brain amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging in glioma patients using low-power steady-state pulsed chemical exchange saturation transfer (CEST) imaging at 7T.

To explore the relationship of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signal intensities with respect to different World Health Organization (WHO) brain tumor grades (II to IV) at 7T.APT-based and NOE-based signals at 7T using low-power steady-state chemical exchange saturation transfer (CEST) were compared among de novo primary gliomas of different WHO grades (II to IV).
Author: 
Pillai JJ
Mark McIntosh,'s picture

A dextran-based probe for the targeted magnetic resonance imaging of tumours expressing prostate-specific membrane antigen.

Safe imaging agents able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran -ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI.
Author: 
van Zijl P
Mark McIntosh,'s picture

MRI techniques to measure arterial and venous cerebral blood volume.

The measurement of cerebral blood volume (CBV) has been the topic of numerous neuroimaging studies. To date, however, most in vivo imaging approaches can only measure CBV summed over all types of blood vessels, including arterial, capillary and venous vessels in the microvasculature (i.e. total CBV or CBVtot).
Author: 
Kim SG
Mark McIntosh,'s picture

Monogenic disorders that mimic the phenotype of Rett syndrome.

Rett syndrome (RTT) is caused by mutations in methyl-CpG-binding protein 2 (MECP2), but defects in a handful of other genes (e.g., CDKL5, FOXG1, MEF2C) can lead to presentations that resemble, but do not completely mirror, classical RTT. In this study, we attempted to identify other monogenic disorders that share features with RTT. We performed a retrospective chart review on n = 319 patients who had undergone clinical whole exome sequencing (WES) for further etiological evaluation of neurodevelopmental diagnoses that remained unexplained despite extensive prior workup.
Author: 
Naidu S
Mark McIntosh,'s picture

Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger Spectrum Disorder.

Zellweger spectrum disorders (ZSDs) are autosomal-recessive disorders that are caused by defects in peroxisome biogenesis due to bi-allelic mutations in any of 13 different PEX genes. Here, we identified seven unrelated individuals affected with an apparent dominant ZSD in whom a heterozygous mutant PEX6 allele (c.2578C>T [p.Arg860Trp]) was overrepresented due to allelic expression imbalance (AEI).
Author: 
Waterham HR
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Mitochondrial DNA Deletions With Low-Level Heteroplasmy in Adult-Onset Myopathy.

We report the cases of 2 patients who presented to our Myositis Center with myalgias and elevated creatine kinase levels. Muscle biopsy showed pathological features consistent with mitochondrial myopathy. In both cases, a single large deletion in mitochondrial DNA at low-level heteroplasmy was identified by next-generation sequencing in muscle tissue. In 1 case, the deletion was identified in muscle tissue but not blood. In both cases, the deletion was only identified on next-generation sequencing of muscle mitochondrial DNA and missed on array comparative genome hybridization testing.
Author: 
Christopher-Stine L
Mark McIntosh,'s picture

Zoledronic acid improves bone histomorphometry in a murine model of Rett syndrome.

Rett syndrome (RTT) is a neurodevelopmental disorder predominately affecting young females, caused by deficiency of the global transcriptional protein methyl CpG binding protein 2 (MeCP2). Osteoblasts express MeCP2 and girls with RTT experience early onset osteoporosis, decreased bone mass and an increased fracture risk. There is no defined treatment for osteoporosis associated with RTT. The present study evaluated the effects of zoledronic acid (ZA), a third generation nitrogen-containing bisphosphonate with primarily anti-osteoclastic activity, in a mouse model of MeCP2 deficiency.
Author: 
Blue ME
Mark McIntosh,'s picture

Longitudinal telomere shortening and early Alzheimer's disease progression in adults with down syndrome.

Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without "mild cognitive impairment" (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population.
Author: 
Silverman WP
Mark McIntosh,'s picture

Brief Report: Self-Injurious Behaviors in Preschool Children with Autism Spectrum Disorder Compared to Other Developmental Delays and Disorders.

We compared the prevalence of self-injurious behaviors (SIB) in preschoolers aged 30-68 months with autism spectrum disorder (ASD) (n = 691) versus other developmental delays and disorders (DD) (n = 977) accounting for sociodemographic, cognitive, and medical factors. SIB prevalence was higher in ASD versus all DD [adjusted odds-ratio (aOR) 2.13 (95% confidence interval (95% CI) 1.53, 2.97)]. In subgroup analyses, SIB prevalence was higher in ASD versus DD without ASD symptoms [aOR 4.42 (95% CI 2.66, 7.33)], but was similar between ASD and DD with ASD symptoms [aOR 1.09 (95% CI 0.68, 1.77)].
Author: 
DiGuiseppi C
Mark McIntosh,'s picture

N-back versus Complex Span Working Memory Training.

Working memory (WM) is the ability to maintain and manipulate task-relevant information in the absence of sensory input. While its improvement through training is of great interest, the degree to which WM training transfers to untrained WM tasks (near transfer) and other untrained cognitive skills (far transfer) remains debated and the mechanism(s) underlying transfer are unclear. Here we hypothesized that a critical feature of dual n-back training is its reliance on maintaining relational information in WM.
Author: 
Courtney SM
Mark McIntosh,'s picture

Global Identification of SUMO Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration.

Proteomics studies have revealed that SUMOylation is widely used posttranslational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown.  Using a human proteome microarray-based activity screen, we identified over 2,500 proteins that undergo SUMO E3-dependent SUMOylation.  We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network.
Author: 
Zhu H
Mark McIntosh,'s picture

Water suppression in the human brain with hypergeometric RF pulses for single-voxel and multi-voxel MR spectroscopy.

To develop and investigate a novel water suppression sequence with hypergeometric pulses at 3 T.Simulations were used to optimize the delays and amplitudes of 5 hypergeometric prepulses, to minimize the residual water over a range of Tand Bvalues. Single-voxel data with hypergeometric water suppression (HGWS) prepulses were acquired in the centrum semiovale, 2 parietal regions, and insula of 7 subjects, and compared with VAPOR water suppression. Magnetic resonance spectroscopic imaging (MRSI) data using both VAPOR and HGWS prepulses were also collected and compared.
Author: 
Barker PB
Mark McIntosh,'s picture

Spatial Hadamard encoding of J-edited spectroscopy using slice-selective editing pulses.

A new approach for simultaneous dual-voxel J-difference spectral editing is described, which uses spatially selective spectral-editing pulses and Hadamard encoding. A theoretical framework for spatial Hadamard editing and reconstruction for parallel acquisition (SHERPA) was developed, applying gradient pulses during the frequency-selective editing pulses. Spectral simulations were performed for either one (gamma-aminobutyric acid, GABA) or two molecules (glutathione and lactate) simultaneously detected in two voxels.
Author: 
Edden RA
Mark McIntosh,'s picture

Isolating Visual and Proprioceptive Components of Motor Sequence Learning in ASD.

In addition to defining impairments in social communication skills, individuals with autism spectrum disorder (ASD) also show impairments in more basic sensory and motor skills. Development of new skills involves integrating information from multiple sensory modalities. This input is then used to form internal models of action that can be accessed when both performing skilled movements, as well as understanding those actions performed by others. Learning skilled gestures is particularly reliant on integration of visual and proprioceptive input.
Author: 
Oberman LM
Mark McIntosh,'s picture

Improved estimation of subject-level functional connectivity using full and partial correlation with empirical Bayes shrinkage.

Reliability of subject-level resting-state functional connectivity (FC) is determined in part by the statistical techniques employed in its estimation. Methods that pool information across subjects to inform estimation of subject-level effects (e.g., Bayesian approaches) have been shown to enhance reliability of subject-level FC. However, fully Bayesian approaches are computationally demanding, while empirical Bayesian approaches typically rely on using repeated measures to estimate the variance components in the model.
Author: 
Lindquist MA
Mark McIntosh,'s picture

Preschool Inhibitory Control Predicts ADHD Group Status and Inhibitory Weakness in School.

Discriminative utility of performance measures of inhibitory control was examined in preschool children with and without ADHD to determine whether performance measures added to diagnostic prediction and to prediction of informant-rated day-to-day executive function.Children ages 4-5 years (N = 105, 61% boys; 54 ADHD, medication-naïve) were assessed using performance measures (Auditory Continuous Performance Test for Preschoolers-Commission errors, Conflicting Motor Response Test, NEPSY Statue) and caregiver (parent, teacher) ratings of inhibition (Behavior Rating Inventory of Executive Functio
Author: 
Mahone EM
Mark McIntosh,'s picture

Reading-Related Causal Attributions for Success and Failure: Dynamic Links With Reading Skill.

The present study investigated the relation among reading skills and attributions, naming speed, and phonological awareness across a wide range of reading skill. Participants were 1,105 school-age children and youths from two understudied populations: African Americans and Hispanic Americans. Individual assessments of children ranging in age from 8 to 15 years were conducted for reading outcomes, cognitive and linguistic predictors of reading, and attributions for success and failure in reading situations.
Author: 
Gruen JR

Bullying, Harassment, and Intimidation of Students with Disabilities in Maryland Public Schools

This presentation will provide an overview of federal and state law and regulations, guidance from the federal government, and policies about bullying, harassment, and intimidations. The presenters will discuss how to address the issue in home, school, and the community, as well as provide tips for service providers and families.

Regulating Technology Use at Home: Tips and Techniques for Children with Autism

Despite the several benefits of children using interactive media and technology, they still face several risks when left unmonitored. It is important for parents to balance technology use and set rules about technology use to avoid these consequences. This presentation will include discussion of these risks, the current recommendations, and several realistic household implementations, including alternative activities to electronic use.

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Kennedy Krieger Institute Announces Retirement of President and CEO

Dr. Gary W. GoldsteinThe Institute’s board of directors is conducting a national search and is expected to name a new CEO in the coming months.
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