Digital Commons Network^™

Fgf-2 Induces Neuronal Death Through Upregulation Of System Xc-, Xiaoqian Liu, Rebecca Albano, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The cystine/glutamate antiporter (system xc-) transports cystine into cell in exchange for glutamate. Fibroblast growth factor-2 (FGF-2) upregulates system xc- selectively on astrocytes, which leads to increased cystine uptake, the substrate for glutathione production, and increased glutamate release. While increased intracellular glutathione can limit oxidative stress, the increased glutamate release can potentially lead to excitotoxicity to neurons. To test this hypothesis, mixed neuronal and glial cortical cultures were treated with FGF-2. Treatment with FGF-2 for 48 h caused a significant neuronal death in these cultures. Cell death was not observed in neuronal-enriched cultures, or astrocyte-enriched …

Exploring The Atomic Structure And Conformational Flexibility Of A 320 Å Long Engineered Viral Fiber Using X-Ray Crystallography., Anshul Bhardwaj, Sherwood R Casjens, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identified in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, …

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Robert Powers Publications

Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …

An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski

Dissertations, Theses, and Capstone Projects

An ethnobotanical, ecological and LC-MS-based chemometric investigation of Phaleria nisidai, a traditional adaptogen containing diterpene esters from Palau, Micronesia

Palau is a country with a rich heritage of traditional medicine still being practiced. One of the most popular and respected remedies in Palau is a tea made from fresh leaves of Phaleria nisidai Kaneh. (Thymelaeaceae). Interviews conducted to determine the use of this plant revealed that it is employed non-specifically to treat a variety of general health concerns. Its use as a prophylactic to keep away sickness, as a 'system cleaner', as well as for strength and energy indicate …

Two Distinct Dynamic Modes Subtend The Detection Of Unexpected Sounds, Jean-Rémi King, Alexandre Gramfort, Aaron Schurger, Lionel Naccache, Stanislas Dehaene

Psychology Faculty Articles and Research

The brain response to auditory novelty comprises two main EEG components: an early mismatch negativity and a late P300. Whereas the former has been proposed to reflect a prediction error, the latter is often associated with working memory updating. Interestingly, these two proposals predict fundamentally different dynamics: prediction errors are thought to propagate serially through several distinct brain areas, while working memory supposes that activity is sustained over time within a stable set of brain areas. Here we test this temporal dissociation by showing how the generalization of brain activity patterns across time can characterize the dynamics of the underlying …

The Multiscale Backbone Of The Human Phenotype Network Based On Biological Pathways, Christian Darabos, Marquitta J. White, Britney E. Graham, Derek N. Leung, Scott M. Williams, Jason H. Moore

Dartmouth Scholarship

Background:

Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes.

Results:

The resulting network has a …

Prion Infection Impairs Cholesterol Metabolism In Neuronal Cells, Huanhuan L. Cui, Belinda Guo, Benjamin Scicluna, Bradley M. Coleman, Victoria A. Lawson, Laura Ellett, Peter J. Meikle, Michael I. Bukrinsky, Nigora Mukhamedova, Dmitri Sviridov, Andrew F. Hill

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Conversion of prion protein (PrP^C) into a pathological isoform (PrP^Sc) during prion infection occurs in lipid rafts and is dependent on cholesterol. Here, we show that prion infection increases the abundance of cholesterol transporter, ATP-binding cassette transporter type A1 (ATP-binding cassette transporter type A1), but reduces cholesterol efflux from neuronal cells leading to the accumulation of cellular cholesterol. Increased abundance of ABCA1 in prion disease was confirmed in prion-infected mice. Mechanistically, conversion of PrP^C to the pathological isoform led to PrP^Sc accumulation in rafts, displacement of ABCA1 from rafts and the cell surface, and …

Detection Of Homocysteine With Bridged Viologen Chemical Probes, Davin Rautiola

Dissertations and Theses

Increased blood plasma concentrations of the aminothiol homocysteine (Hcy) are associated with a variety of disease states including those which cause impaired renal function, many forms of cardiovascular disease, and neurodegenerative diseases such as Alzheimer's. Therefore, Hcy has the potential to be a significant diagnostic biomarker. Routine monitoring of Hcy plasma concentration is encumbered by the time and resources required to quantify Hcy using currently accepted instrumental analysis methods. As part of the continuing effort to develop a quick, reliable, inexpensive, and user-friendly test to quantify Hcy at the point of care, we have designed a series of novel colorimetric …

The Evolutionary Young Mir-1290 Favors Mitotic Exit And Differentiation Of Human Neural Progenitors Through Altering The Cell Cycle Proteins., Sowmya V. Yelamanchili, Brenda M. Morsey, Emily B. Harrison, D. A. Rennard, Kathleen M. Emanuel, I Thapa, D. R. Bastola, H. S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We …

Methods And Matrices: Approaches To Identifying Mirnas For Nasopharyngeal Carcinoma, Jordan L. Plieskatt, Gabriel Rinaldi, Yanjung Feng, Paul H. Levine, Samantha Easley, Elizabeth Martinez, Salman Hashmi, Nader Sadeghi, Paul J. Brindley, Jeffrey M. Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

We tested two miRNA discovery workflows on two sample sources for miRNAs associated with NPC. In the first workflow, we assumed that NPC tumor tissue would be enriched for miRNAs, so we compared miRNA expression in FFPE from NPC cases and controls using microarray and RNA-Seq technologies. Candidate miRNAs from both technologies were verified by qPCR in FFPE and sera from an independent NPC sample set. In a second workflow, we directly interrogated NPC case and control sera by RNA-Seq for c-miRNAs associated with NPC, with candidate c-miRNAs verified by qPCR in the sera from the same independent NPC sample …

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …

Epc-Derived Microvesicles Protect Cardiomyocytes From Ang Ii-Induced Hypertrophy And Apoptosis, Shenhong Gu, Wei Zhang, Ji Chen, Ruilian Ma, Xiang Xiao, Xiaotang Ma, Zhen Yao, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Cell-released microvesicles (MVs) represent a novel way of cell-to-cell communication. Previous evidence indicates that endothelial progenitor cells (EPCs)-derived MVs can modulate endothelial cell survival and proliferation. In this study, we evaluated whether EPC-MVs protect cardiomyocytes (CMs) against angiotensin II (Ang II)-induced hypertrophy and apoptosis. The H9c2 CMs were exposed to Ang II in the presence or absence of EPC-MVs. Cell viability, apoptosis, surface area and β-myosin heavy chain (β-MHC) expression were analyzed. Meanwhile, reactive oxygen species (ROS), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS), and their phosphorylated proteins (p-Akt, p-eNOS) were measured. Phosphatidylinositol-3-kinase (PI3K) and NOS inhibitors were used …

Aortic Aneurysms In Loeys-Dietz Syndrome - A Tale Of Two Pathways?, Frank Davis, Debra L. Rateri, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by skeletal abnormalities, craniofacial malformations, and a high predisposition for aortic aneurysm. In this issue of the JCI, Gallo et al. developed transgenic mouse strains harboring missense mutations in the genes encoding type I or II TGF-β receptors. These mice exhibited several LDS-associated phenotypes. Despite being functionally defective, the mutated receptors enhanced TGF-β signaling in vivo, inferred by detection of increased levels of phosphorylated Smad2. Aortic aneurysms in these LDS mice were ablated by treatment with the Ang II type 1 (AT1) receptor antagonist losartan. The results from this …

A New Rhesus Macaque Assembly And Annotation For Next-Generation Sequencing Analyses, Aleksey V. Zimin, Adam S. Cornish, Mnirnal D. Maudhoo, Robert M. Gibbs, Xiongfei Zhang, Sanjit Pandey, Daniel T. Meehan, Kristin Wipfler, Steven E. Bosinger, Zachary P. Johnson, Gregory K. Tharp, Guillaume Marçais, Michael Roberts, Betsy Ferguson, Howard S. Fox, Todd Treangen, Steven L. Salzberg, James A. Yorke, Robert B. Norgren Jr.

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.0, is also available but is substantially more fragmented than rheMac2 with smaller contigs and scaffolds. Annotations for these two assemblies are limited in completeness and accuracy. High quality assembly and annotation files are required for a wide range of studies including expression, genetic and evolutionary analyses.

RESULTS: We report a new de novo assembly of the …

Molecular Genetic Evidence For Overlap Between General Cognitive Ability And Risk For Schizophrenia: A Report From The Cognitive Genomics Consortium (Cogent), T. Lencz, E. Knowles, G. Davies, S. Guha, D. C. Liewald, J. M. Starr, S. Djurovic, I. Melle, K. Sundet, A. Christoforou, I. Reinvang, S. Mukherjee, P. Derosse, A. Lundervold, V. M. Steen, M. John, T. Espeseth, K. Raikkonen, E. Widen, A. Palotie, J. G. Eriksson, I. Giegling, B. Konte, M. Ikeda, P. Roussos, S. Giakoumaki, K. E. Burdick, A. Payton, W. Ollier, M. Horan, G. Donohoe, D. Morris, A. Corvin, M. Gill, N. Pendleton, N. Iwata, A. Darvasi, P. Bitsios, D. Rujescu, J. Lahti, S. L. Hellard, M. C. Keller, O. A. Andreassen, I. J. Deary, D. C. Glahn, Anil Malhotra

Journal Articles

It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia (SCZ), evident before full illness onset and independent of medication. The possibility of genetic overlap between risk for SCZ and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with SCZ; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of SCZ have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of …

The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging, C. M. Marano, C. I. Workman, C. H. Lyman, E. Kramer, C. R. Hermann, Y. L. Ma, V. Dhawan, T. Chaly, D. Eidelberg, G. S. Smith

Journal Articles

Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer's disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n = 16) was correlated with PET scans of cerebral glucose metabolism …

Biological Insights From 108 Schizophrenia-Associated Genetic Loci, S. Ripke, B. M. Neale, A. Corvin, J. T. R. Walters, K. H. Farh, T. Lencz, A. K. Malhotra, Consortium Psychiat Genomics, Conso Psychosis Endophenotypes Int, Consor Wellcome Trust Case-Control, +292 Additional Authors

Journal Articles

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and …

Functional Development In Clinical High Risk Youth: Prediction Of Schizophrenia Versus Other Psychotic Disorders, S. I. Tarbox, J. Addington, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, D. O. Perkins, L. J. Seidman, M. T. Tsuang, E. F. Walker, S. W. Woods, +2 Additional Authors

Journal Articles

This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early …

Moderator Effects Of Working Memory On The Stability Of Adhd Symptoms By Dopamine Receptor Gene Polymorphisms During Development, J. Trampush, M. M. Jacobs, Y. L. Hurd, J. H. Newcorn, J. M. Halperin

Journal Articles

We tested the hypothesis that dopamine D1 and D2 receptor gene (DRD1 and DRD2, respectively) polymorphisms and the development of working memory skills can interact to influence symptom change over 10 years in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, we examined whether improvements in working memory maintenance and manipulation from childhood to early adulthood predicted the reduction of ADHD symptoms as a function of allelic variation in DRD1 and DRD2. Participants were 76 7-11-year-old children with ADHD who were genotyped and prospectively followed for almost 10 years. ADHD symptoms were rated using the Attention Problems scale on the Child Behavior …

Rdocs Redux, D. R. Weinberger, T. Goldberg

Journal Articles

No abstract provided.

Bone Morphogenetic Protein-Focused Strategies To Induce Cytotoxicity In Lung Cancer Cells, A. Fotinos, N. Nagarajan, A. S. Martins, D. T. Fritz, D. Garsetti, A. T. Lee, C. C. Hong, M. B. Rogers

Journal Articles

Background: High bone morphogenetic protein (BMP)-2 expression in lung carcinoma correlates with poor patient prognosis. The present study explored strategies to repress BMP signaling. Materials and Methods: The cytotoxicity of BMP2-knockdown, dorsomorphin derivatives, and microRNAs was tested in transformed and non-transformed lung cells. Microarray analyses of 1,145 microRNAs in A549 lung adenocarcinoma cells and two other transformed lung cell types relative to BEAS-2B bronchial epithelial cells were performed. Results: Reduced BMP2 synthesis inhibited A549 cell growth. The dorsomorphin derivative LDN-193189, but not DMH1 or DMH4, was strongly cytotoxic towards A549 cells, but not towards BEAS-2B cells. Microarray analysis revealed that …

Dietary Regimens Modify Early Onset Of Obesity In Mice Haploinsufficient For Rai1, Joseph T. Alaimo, Natalie H. Hahn, Sureni V. Mullegama, Sarah H. Elsea

Human and Molecular Genetics Publications

Smith-Magenis syndrome is a complex genomic disorder in which a majority of individuals are obese by adolescence. While an interstitial deletion of chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene alone results in most features of the disorder. Previous studies have shown that heterozygous knockout of Rai1 results in an obese phenotype in mice and that Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an altered transmission pattern of the mutant Rai1 allele, complicating large, extended studies in these models. In this study, we show that breeding C57Bl/6J Rai1+/−mice with FVB/NJ to …

Chmp1 Negatively Regulates Epidermal Growth Factor Signaling In The Drosophila Wing, Meagan Elisabeth Valentine

Theses, Dissertations and Capstones

A critical step in cellular signaling through transmembrane receptors is the down-regulation of activated receptors through the multivesicular body (MVB) pathway to the lysosome. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Though the ESCRT-III complex provides the core function of the ESCRT machinery, it is the least characterized of the ESCRT complexes. The Chmp1 protein is an ESCRT-III component and a putative tumor suppressor that has been linked to pancreatic and renal cancers in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not …

Cardiovascular Aging In The Female F344xbn Rat Model, Jacqueline C. Fannin

Theses, Dissertations and Capstones

Despite continued advances in medical care, cardiovascular disease (CVD) remains the leading cause of death for American women [1]. Although humans and non-human primates are the only mammals to experience menses, rodent models are commonly used to study age-associated cardiovascular alterations due to similar ovarian aging, low expense, and short lifetime to investigate cardiovascular aging. Previous studies have found that aging in the female rodent is characterized by increased ventricular apoptosis, elevations in oxidative-nitrosative stress, ventricular remodeling, increased collagen content, mild systolic and diastolic dysfunction, and reduced occurrence of arrhythmias compared to males [2-7]. Similarly, age-associated alterations in the female …

Fusion, 2014, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Inhibition Of Amp-Activated Protein Kinase Signaling Alleviates Impairments In Hippocampal Synaptic Plasticity Induced By Amyloid Beta, T. Ma, Y. R. Chen, V. Vingtdeux, H. T. Zhao, B. Viollet, P. Marambaud, E. Klann

Journal Articles

The AMP-activated protein kinase (AMPK) is a Ser/Thr kinase that is activated in response to low-energy states to coordinate multiple signaling pathways to maintain cellular energy homeostasis. Dysregulation of AMPK signaling has been observed in Alzheimer's disease (AD), which is associated with abnormal neuronal energy metabolism. In the current study we tested the hypothesis that aberrant AMPK signaling underlies AD-associated synaptic plasticity impairments by using pharmacological and genetic approaches. We found that amyloid beta (A beta)-induced inhibition of long-term potentiation (LTP) and enhancement of long-term depression were corrected by the AMPK inhibitor compound C (CC). Similarly, LTP impairments in APP/PS1 …

Effect Of The Calhm1 G330d And R154h Human Variants On The Control Of Cytosolic Ca2+ And A Beta Levels, V. Vingtdeux, J. E. Tanis, P. Chandakkar, H. T. Zhao, U. Dreses-Werringloer, F. Campagne, J. K. Foskett, P. Marambaud

Journal Articles

CALHM1 is a plasma membrane voltage-gated Ca2+-permeable ion channel that controls amyloid-beta (A beta) metabolism and is potentially involved in the onset of Alzheimer's disease (AD). Recently, Rubio-Moscardo et al. (PLoS One (2013) 8: e74203) reported the identification of two CALHM1 variants, G330D and R154H, in early-onset AD (EOAD) patients. The authors provided evidence that these two human variants were rare and resulted in a complete loss of CALHM1 function. Recent publicly available large-scale exome sequencing data confirmed that R154H is a rare CALHM1 variant (minor allele frequency (MAF) = 0.015%), but that G330D is not (MAF = 3.5% in …

A Disease-Specific Metabolic Brain Network Associated With Corticobasal Degeneration, M. Niethammer, C. C. Tang, A. Feigin, P. J. Allen, L. Heinen, S. Hellwig, F. Amtage, E. Hanspal, J. P. Vonsattel, D. Eidelberg, +3 Addtional Authors

Journal Articles

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 +/- 5.7 years) underwent metabolic brain imaging with 18 F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age …

Thalamocortical Connectivity Correlates With Phenotypic Variability In Dystonia, An Vo, W. Sako, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg

Journal Articles

Dystonia is a brain disorder characterized by abnormal involuntary movements without defining neuropathological changes. The disease is often inherited as an autosomal-dominant trait with incomplete penetrance. Individuals with dystonia, whether inherited or sporadic, exhibit striking phenotypic variability, with marked differences in the somatic distribution and severity of clinical manifestations. In the current study, we used magnetic resonance diffusion tensor imaging to identify microstructural changes associated with specific limb manifestations. Functional MRI was used to localize specific limb regions within the somatosensory cortex. Microstructural integrity was preserved when assessed in subrolandic white matter regions somatotopically related to the clinically involved limbs, …

Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond

Journal Articles

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and antinuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb + mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb + mice, metabolism declined at the site of BBB breach in the first 2 …