Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, 2018 Boston University
Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz. Da Rocha, Cheng Zhang, Wai Haung Yu, John D. Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin
Open Access Articles
The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer's disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies ...
Predicting Gains With Visuospatial Training After Stroke Using An Eeg Measure Of Frontoparietal Circuit Function, 2018 University of California, Irvine
Predicting Gains With Visuospatial Training After Stroke Using An Eeg Measure Of Frontoparietal Circuit Function, Robert J. Zhou, Hossein M. Hondori, Maryam Khademi, Jessica M. Cassidy, Katherine M. Wu, Derek Z. Yang, Nikhita Kathuria, Fareshte R. Erani, Lucy Dodakian, Alison Mckenzie, Cristina V. Lopes, Walt Scacchi, Ramesh Srinivasan, Steven C. Cramer
Physical Therapy Faculty Articles and Research
The heterogeneity of stroke prompts the need for predictors of individual treatment response to rehabilitation therapies. We previously studied healthy subjects with EEG and identified a frontoparietal circuit in which activity predicted training-related gains in visuomotor tracking. Here we asked whether activity in this same frontoparietal circuit also predicts training-related gains in visuomotor tracking in patients with chronic hemiparetic stroke. Subjects (n = 12) underwent dense-array EEG recording at rest, then received 8 sessions of visuomotor tracking training delivered via home-based telehealth methods. Subjects showed significant training-related gains in the primary behavioral endpoint, Success Rate score on a standardized test of ...
Guidance For Switching From Off-Label Antipsychotics To Pimavanserin For Parkinson’S Disease Psychosis: An Expert Consensus, 2018 Washington University in St. Louis
Guidance For Switching From Off-Label Antipsychotics To Pimavanserin For Parkinson’S Disease Psychosis: An Expert Consensus, Kevin J. Black, Henry Nasrallah, Stuart Isaacson, Mark Stacy, Rajesh Pahwa, Charles H. Adler, Gustavo Alva, Jeffrey W. Cooney, Daniel Kremens, Matthew A. Menza, Jonathan M. Meyer, Ashwin A. Patkar, Tanya Simuni, Debbi A. Morrissette, Stephen Stahl
Kevin J. Black, MD
Loss Of Sarm1 Does Not Suppress Motor Neuron Degeneration In The Sod1g93a Mouse Model Of Amyotrophic Lateral Sclerosis, 2018 University of Massachusetts Medical School
Loss Of Sarm1 Does Not Suppress Motor Neuron Degeneration In The Sod1g93a Mouse Model Of Amyotrophic Lateral Sclerosis, Owen M. Peters, Elizabeth A. Lewis, Jeannette M. Osterloh, Alexandra Weiss, Johnny Salameh, Jake P. Metterville, Robert H. Brown Jr., Marc R. Freeman
Neurobiology Publications and Presentations
Axon degeneration occurs in all neurodegenerative diseases, but the molecular pathways regulating axon destruction during neurodegeneration are poorly understood. Sterile Alpha and TIR Motif Containing 1 (Sarm1) is an essential component of the prodegenerative pathway driving axon degeneration after axotomy and represents an appealing target for therapeutic intervention in neurological conditions involving axon loss. Amyotrophic lateral sclerosis (ALS) is characterized by rapid, progressive motor neuron degeneration and muscle atrophy, causing paralysis and death. Patient tissue and animal models of ALS show destruction of upper and lower motor neuron cell bodies and loss of their associated axons. Here, we investigate whether ...
Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, 2018 St. Charles Community College
Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, Allison Houghton, Jennifer Walters, Mary Hong, Dhruv Joshi, Hee Jung Chung
Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal ...
Als-Associated Missense And Nonsense Tbk1 Mutations Can Both Cause Loss Of Kinase Function, 2018 King's College London
Als-Associated Missense And Nonsense Tbk1 Mutations Can Both Cause Loss Of Kinase Function, Martina De Majo, Kevin P. Kenna, Robert H. Brown Jr., John E. Landers, Christopher E. Shaw
Open Access Articles
Mutations in TANK binding kinase 1 (TBK1) have been linked to amyotrophic lateral sclerosis. Some TBK1 variants are nonsense and are predicted to cause disease through haploinsufficiency; however, many other mutations are missense with unknown functional effects. We exome sequenced 699 familial amyotrophic lateral sclerosis patients and identified 16 TBK1 novel or extremely rare protein-changing variants. We characterized a subset of these: p.G217R, p.R357X, and p.C471Y. Here, we show that the p.R357X and p.G217R both abolish the ability of TBK1 to phosphorylate 2 of its kinase targets, IRF3 and optineurin, and to undergo phosphorylation. They ...
Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., 2018 George Washington University
Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller
Anatomy and Regenerative Biology Faculty Publications
Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal ...
A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, 2018 University of Massachusetts Medical School
A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, Dan Wang, Shaoyong Li, Dominic J. Gessler, Jun Xie, Li Zhong, Jia Li, Karen Tran, Kim Van Vliet, Lingzhi Ren, Qin Su, Ran He, Jason E. Goetzmann, Terence R. Flotte, Mavis Agbandje-Mckenna, Guangping Gao
Open Access Articles
Adeno-associated virus (AAV) has provided the gene therapy field with the most powerful in vivo gene delivery vector to realize safe, efficacious, and sustainable therapeutic gene expression. Because many clinically relevant properties of AAV-based vectors are governed by the capsid, much research effort has been devoted to the development of AAV capsids for desired features. Here, we combine AAV capsid discovery from nature and rational engineering to report an AAV9 capsid variant, designated as AAV9.HR, which retains AAV9's capability to traverse the blood-brain barrier and transduce neurons. This variant shows reduced transduction in peripheral tissues when delivered through ...
A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, 2018 University of Massachusetts Medical School
A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, Lindsay S. Romo, Emily S. Mohn, Neil Aronin
RNA Therapeutics Institute Publications
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation that expands the polyglutamine (CAG) repeat in exon 1 of the huntingtin (HTT) gene. Wild-type HTT protein interacts with other proteins to protect cells against toxic stimuli, mediate vesicle transport and endocytosis, and modulate synaptic activity. Mutant HTT protein disrupts autophagy, vesicle transport, neurotransmitter signaling, and mitochondrial function. Although many of the activities of wild-type HTT protein and the toxicities of mutant HTT protein are characterized, less is known about the activities of HTT mRNA. Most putative HD therapies aim to target mutant HTT mRNA before it ...
Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, 2018 Central South University
Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng
Open Access Articles
EphrinB3 is important in the regulation of cell proliferation, differentiation and migration via cellcell contact, and can activate the reelin pathway during brain development. However, the effect of ephrinB3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrinB3 in pilocarpineinduced status epilepticus (SE) rats was investigated. SYBR Greenbased reverse transcriptionquantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrinB3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis ...
High-Resolution Imaging Of Myeloperoxidase Activity Sensors In Human Cerebrovascular Disease, 2018 New York University School of Medicine
High-Resolution Imaging Of Myeloperoxidase Activity Sensors In Human Cerebrovascular Disease, Youssef Z. Wadghiri, Dung Minh. Hoang, Anita M. Leporati, Matthew J. Gounis, Aurora Rodriguez-Rodriguez, Mary L. Mazzanti, John P. Weaver, Ajay K. Wakhloo, Peter Caravan, Alexei A. Bogdanov Jr
Radiology Publications and Presentations
Progress in clinical development of magnetic resonance imaging (MRI) substrate-sensors of enzymatic activity has been slow partly due to the lack of human efficacy data. We report here a strategy that may serve as a shortcut from bench to bedside. We tested ultra high-resolution 7T MRI (microMRI) of human surgical histology sections in a 3-year IRB approved, HIPAA compliant study of surgically clipped brain aneurysms. microMRI was used for assessing the efficacy of MRI substrate-sensors that detect myeloperoxidase activity in inflammation. The efficacy of Gd-5HT-DOTAGA, a novel myeloperoxidase (MPO) imaging agent synthesized by using a highly stable gadolinium (III) chelate ...
Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, 2018 Center for Nanomedicine, College of Engineering and Computing, Florida International University, Miami, Florida
Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev
This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson’s Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration ...
Role Of The Dorsal Striatum In Learning And Decision Making, 2018 The University of Western Ontario
Role Of The Dorsal Striatum In Learning And Decision Making, Nole M. Hiebert
Electronic Thesis and Dissertation Repository
The striatum, the input region of the basal ganglia, has been shown to mediate many cognitive functions. The striatum itself can be functionally segregated into dorsal (DS) and ventral striatum (VS). For more than 60 years, DS has been reported to mediate stimulus-response learning, though evidence has been accruing pointing to a role in decision making. These literatures have been growing independently and an aim of this thesis was to bridge these two bodies of knowledge. We directly investigated the role of DS in stimulus-response learning versus decision making using functional magnetic resonance imaging (fMRI) in patients with Parkinson’s ...
Assistive Utensil: A Spork For Hand Tremors And Spatial Awareness, 2018 City University of New York (CUNY)
Assistive Utensil: A Spork For Hand Tremors And Spatial Awareness, Ana Font Hernandez, Jacob Kabariti, Troy Taylor
Publications and Research
In this poster, we present a 3D printed solution for hand tremors and special awareness. Our spork is an assistive device designed and 3D printed for patients suffering from scleroderma, systemic sclerosis, Parkinson's, multiple sclerosis, drug withdrawal, etc. The scale-based handle will act as a counterweight to offset the contents on the other end and reduce shakiness. The larger grip allows an easy and comfortable hold. The product will be 3D printed for a customizable fit and at an affordable price. Lastly, the product will include a haptic feedback sensor to assist the visually impaired in locating food contents ...
Amygdala Corticofugal Input Shapes Mitral Cell Responses In The Accessory Olfactory Bulb, 2018 George Washington University
Amygdala Corticofugal Input Shapes Mitral Cell Responses In The Accessory Olfactory Bulb, Livio Oboti, Eleonora Russo, Tuyen Tran, Daniel Durstewitz, Joshua G. Corbin
Pediatrics Faculty Publications
Interconnections between the olfactory bulb and the amygdala are a major pathway for triggering strong behavioral responses to a variety of odorants. However, while this broad mapping has been established, the patterns of amygdala feedback connectivity and the influence on olfactory circuitry remain unknown. Here, using a combination of neuronal tracing approaches, we dissect the connectivity of a cortical amygdala [posteromedial cortical nucleus (PmCo)] feedback circuit innervating the mouse accessory olfactory bulb. Optogenetic activation of PmCo feedback mainly results in feedforward mitral cell (MC) inhibition through direct excitation of GABAergic granule cells. In addition, LED-driven activity of corticofugal afferents increases ...
Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin
Senior Honors Theses
The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research ...
Identification Of Epigenetic Regulators Of Dux4-Fl For Targeted Therapy Of Facioscapulohumeral Muscular Dystrophy, 2018 University of Massachusetts Medical School
Identification Of Epigenetic Regulators Of Dux4-Fl For Targeted Therapy Of Facioscapulohumeral Muscular Dystrophy, Charis L. Himeda, Takako I. Jones, Ching-Man A. Virbasius, Lihua Julie Zhu, Michael R. Green, Peter L. Jones
Open Access Articles
Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic de-repression of the disease locus, leading to pathogenic misexpression of the DUX4 gene in skeletal muscle. While the factors and pathways involved in normal repression of the FSHD locus in healthy cells have been well characterized, very little is known about those responsible for the aberrant activation of DUX4-fl in FSHD myocytes. Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes. We confirmed several of the strongest and most specific candidates (ASH1L, BRD2, KDM4C, and ...
Ethical Dilemma Of Alzheimer's Disease And Informed Consent, 2018 Augustana College, Rock Island Illinois
Ethical Dilemma Of Alzheimer's Disease And Informed Consent, Daenia La Rodé
Augustana Center for the Study of Ethics Essay Contest
No abstract provided.
Haplotype Analysis Of Apoe Intragenic Snps, 2018 Novosibirsk State University
Haplotype Analysis Of Apoe Intragenic Snps, Vladimir N. Babenko, Dmitry A. Afonnikov, Elena V. Ignatieva, Anton V. Klimov, Fedor E. Gusev, Evgeny I. Rogaev
Open Access Articles
BACKGROUND: APOE epsilon4 allele is most common genetic risk factor for Alzheimer's disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE epsilon4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals.
RESULTS: We performed APOE gene haplotype analysis for a short block of five SNPs ...
Motor Subtypes Of Parkinson’S Disease Can Be Identified By Frequency Component Of Postural Stability, 2018 Arizona State University
Motor Subtypes Of Parkinson’S Disease Can Be Identified By Frequency Component Of Postural Stability, Saba Rezvanian, Thurmon Lockhart, Christopher Frames, Rahul Soangra, Abraham Lieberman
Physical Therapy Faculty Articles and Research
Parkinson’s disease (PD) can be divided into two subtypes based on clinical features—namely tremor dominant (TD) and postural instability and gait difficulty (PIGD). This categorization is important at the early stage of PD, since identifying the subtypes can help to predict the clinical progression of the disease. Accordingly, correctly diagnosing subtypes is critical in initiating appropriate early interventions and tracking the progression of the disease. However, as the disease progresses, it becomes increasingly difficult to further distinguish those attributes that are relevant to the subtypes. In this study, we investigated whether a method using the standing center of ...