The University of Western Ontario
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Regis University
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University of Tennessee, Knoxville
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East Tennessee State University
University of Pennsylvania
Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype,
2021
University of Toronto
Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype, Farah Qaiser, Yue Yin, Carolyn B. Mervis, Colleen A. Morris, Bonita P. Klein-Tasman, Elaine Tam, Lucy R. Osborne, Ryan K.C. Yuen
School of Medicine Faculty Publications
© 2021, The Author(s). Background: 7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD). Results: We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two ...
Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment,
2021
CUNY Graduate Center
Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer
Publications and Research
Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons ...
Targeting Ampa Receptor Modulation During Early Life Adversity: A Mediator For Threat Associated Memories,
2021
The Graduate Center, City University of New York
Targeting Ampa Receptor Modulation During Early Life Adversity: A Mediator For Threat Associated Memories, Roseanna M. Zanca
Dissertations, Theses, and Capstone Projects
Early life adversity (ELA) is the exposure to a single or to multiple traumatic events before the age of 18 that go beyond the child’s coping. These adverse events are often exacerbated during adolescence particularly when cognitive performance is compromised. Adolescents who experienced ELA may show symptoms of post-traumatic stress disorder (PTSD), while not vividly recalling the early life trauma. These individuals show atypical connectivity between prefrontal-amygdala and hippocampus, all of which is associated with an increased risk of experiencing a traumatic event again later in life. While clinical research has increasingly stressed the importance in addressing the long-lasting ...
Expression And Subcellular Localization Of Circrnas Dysregulated Als That Are Encoded In Cytoskeletal Protein Genes,
2021
The University of Western Ontario
Expression And Subcellular Localization Of Circrnas Dysregulated Als That Are Encoded In Cytoskeletal Protein Genes, Asieh Alikhah
Electronic Thesis and Dissertation Repository
Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disorder that causes the death of motor neurons. While alterations in the metabolism of RNA, including RNA-binding proteins have been linked to the pathogenesis of ALS, our understanding of the role of non-coding RNAs including circRNAs is less well developed. In this study, using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence (IF) with markers of RNP granules, I investigated the effect of osmotic stress on the localization and expression of a selection of circRNAs whose expression is dysregulated in ALS. Alteration in the number of granules for ...
Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing,
2021
University of Connecticut
Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He
Honors Scholar Theses
Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...
Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing,
2021
University of Connecticut
Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He
University Scholar Projects
Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...
Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines,
2021
City University of New York (CUNY)
Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich
Student Theses
Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary ...
Vitamin B12 Deficiency Does Not Stimulate Amyloid-Beta Toxicity In A Ceanorhabditis Elegans Model Of Alzheimer’S Disease,
2021
East Tennessee State University
Vitamin B12 Deficiency Does Not Stimulate Amyloid-Beta Toxicity In A Ceanorhabditis Elegans Model Of Alzheimer’S Disease, Opeyemi F. Showemimo
Electronic Theses and Dissertations
Alzheimer’s disease (AD) is symptomized by amyloid-beta plaques in the brain and accounts for more than 65 percent of dementia cases. Vitamin B12 (cobalamin) deficiency can result in similar cognitive impairment and roughly 15% of the elderly are vitamin B12 deficient. Vitamin B12 deficiency results in the accumulation of toxic methylmalonic acid and homocysteine. Hyperhomocysteinemia is a strong risk factor for AD. To test if vitamin B12 deficiency stimulates amyloid-beta toxicity, Caenorhabditis elegans expressing amyloid-beta in muscle were fed either vitamin B12-deficient OP50-1 or vitamin B12-rich HT115(DE3) E. coli bacteria. Increased amyloid-beta toxicity was found in worms fed ...
Translational Fidelity And Its Role In Neuronal Homeostasis,
2021
University of Maine
Translational Fidelity And Its Role In Neuronal Homeostasis, Markus Terrey
Electronic Theses and Dissertations
The process of translation, which refers to decoding genetic information from mRNA to protein, is vital for all cellular function. Translational fidelity starts at the level of aminoacylation of transfer RNAs (tRNA). This reaction is catalyzed by aminoacyl tRNA synthetases where each amino acid is transferred to its corresponding cognate tRNA. Because tRNAs harbor the anticodon sequence to decodes a particular mRNA codon, the specific aminoacylation of the tRNA with a cognate amino acid establishes the rules of decoding genetic code into proteins. Aminoacylated tRNAs are then delivered to ribosomes, where ribosomes in a highly organized manner need to accurately ...
Psychedelics Can Save: The Scientific And Social Case For Rescheduling Psychedelic Compounds,
2021
University of Tennessee, Knoxville
Psychedelics Can Save: The Scientific And Social Case For Rescheduling Psychedelic Compounds, Galen M. Fader
Chancellor’s Honors Program Projects
No abstract provided.
Npy Expression Of Low-Birth Weight Offspring In Nutrient-Restricted Utero,
2021
Susquehanna University
Npy Expression Of Low-Birth Weight Offspring In Nutrient-Restricted Utero, Janine Levandowski, Holly Young
Senior Scholars Day
No abstract provided.
Validation Of Induced Microglia-Like Cells (Img Cells) For Future Studies Of Brain Diseases,
2021
University of Nevada, Las Vegas
Validation Of Induced Microglia-Like Cells (Img Cells) For Future Studies Of Brain Diseases, Atoshi Banerjee, Yimei Lu, Kenny Do, Travis Mize, Xiaogang Wu, Xiangning Chen, Jingchun Chen
School of Medicine Faculty Publications
Microglia are the primary resident immune cells of the central nervous system that maintain physiological homeostasis in the brain and contribute to the pathogenesis of many psychiatric disorders and neurodegenerative diseases. Due to the lack of appropriate human cellular models, it is difficult to study the basic pathophysiological processes linking microglia to brain diseases. In this study, we adopted a microglia-like cellular model derived from peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34). We characterized and validated this in vitro cellular model by morphology, immunocytochemistry, gene expression profiles, and functional study. Our results indicated that the iMG ...
Anhedonia And Its Intervention In Depressive Adults: New Developments Based On Research Domain Criteria (Rdoc) In Mental Illnesses,
2021
Faculty of Psychology, Southwest University, Chongqing 400715, China
Anhedonia And Its Intervention In Depressive Adults: New Developments Based On Research Domain Criteria (Rdoc) In Mental Illnesses, J. Mao, J. Yuan
Stress and Brain
Anhedonia, as one of the core symptoms of depression, is of great significance for the diagnosis and treatment of depression. Traditionally, anhedonia has been referred to as "loss of pleasure" , while the recent research emphasizes that anhedonia is a complex and multidimensional construct based on reward processing impairment. Exploring different manifestations of anhedonia and developing the corresponding interventions have become indispensable in the current research of depression. Based on the positive valence system of the Research Domain Criteria (RDoC), this paper firstly demonstrates that the anhedonia of depressive adults are mainly characterized by the impairments in anticipatory pleasure, incentive motivation ...
Exposure To Single Prolonged Stress Fails To Induce Anxiety-Like Behavior In Mice,
2021
Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, China
Exposure To Single Prolonged Stress Fails To Induce Anxiety-Like Behavior In Mice, W-J. You, Y. He, W-Z. Liu, Yu-Ge Zhu, Ping Hu, Bing-Xing Pan, Wen-Hua Zhang
Stress and Brain
Single prolonged stress (SPS) is a well-established and most frequently used rat model to induce post-traumatic stress disorder (PTSD)-like symptoms, which helps to understand the neurobiological mechanisms as well as developing novel therapeutic strategies for PTSD. However, whether such stress model works efficiently in mice remains unknown. In the present study, we established a mouse SPS (mSPS) model by exposing C57BL/6J mice to a series of multimodal stressors on a single day, then the anxiety-like behavior was measured by open-field test, elevated plus maze test, dark-light box, and novelty-suppressed feeding test. Our results showed that mSPS had no ...
A Meta-Analysis Of Brain Dna Methylation Across Sex, Age, And Alzheimer's Disease Points For Accelerated Epigenetic Aging In Neurodegeneration,
2021
Institute of Neurological Sciences of Bologna
A Meta-Analysis Of Brain Dna Methylation Across Sex, Age, And Alzheimer's Disease Points For Accelerated Epigenetic Aging In Neurodegeneration, Camilla Pellegrini, Danielle Fernandes Durso, Maria Giulia Bacalini
Open Access Publications by UMMS Authors
Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of four brain regions (temporal, frontal, entorhinal cortex, and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age-, and AD-associated epigenetic profiles. In one of these datasets it was also possible to distinguish 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC ...
Quantifying And Mitigating Motor Phenotypes Induced By Antisense Oligonucleotides In The Central Nervous System [Preprint],
2021
University of Massachusetts Medical School
Quantifying And Mitigating Motor Phenotypes Induced By Antisense Oligonucleotides In The Central Nervous System [Preprint], Michael P. Moazami, Julia M. Rembetsy-Brown, Feng Wang, Pranathi Meda Krishnamurthy, Alexandra Weiss, Miklos G. Marosfoi, Robert M. King, Mona Motwani, Heather L. Gray-Edwards, Katherine A. Fitzgerald, Robert H. Brown Jr., Jonathan K. Watts
University of Massachusetts Medical School Faculty Publications
Antisense oligonucleotides (ASOs) are emerging as a promising class of therapeutics for neurological diseases. When injected directly into the cerebrospinal fluid, ASOs distribute broadly across brain regions and exert long-lasting therapeutic effects. However, many phosphorothioate (PS)-modified gapmer ASOs show transient motor phenotypes when injected into the cerebrospinal fluid, ranging from reduced motor activity to ataxia or acute seizure-like phenotypes. The effect of sugar and phosphate modifications on these phenotypes has not previously been systematically studied. Using a behavioral scoring assay customized to reflect the timing and nature of these effects, we show that both sugar and phosphate modifications influence ...
Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex,
2021
The Graduate Center, City University of New York
Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich
Dissertations, Theses, and Capstone Projects
Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of ...
Glial Cell Dysfunction In C9orf72-Related Amyotrophic Lateral Sclerosis And Frontotemporal Dementia,
2021
University of Massachusetts Medical School
Glial Cell Dysfunction In C9orf72-Related Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Mehdi Ghasemi, Kiandokht Keyhanian, Catherine Douthwright
Open Access Publications by UMMS Authors
Since the discovery of the chromosome 9 open reading frame 72 (C9orf72) repeat expansion mutation in 2011 as the most common genetic abnormality in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and frontotemporal dementia (FTD), progress in understanding the signaling pathways related to this mutation can only be described as intriguing. Two major theories have been suggested-(i) loss of function or haploinsufficiency and (ii) toxic gain of function from either C9orf72 repeat RNA or dipeptide repeat proteins (DPRs) generated from repeat-associated non-ATG (RAN) translation. Each theory has provided various signaling pathways that potentially participate in ...
Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation,
2021
University of Nevada, Las Vegas
Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines
Psychology Faculty Publications
© 2021, The Author(s). Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we ...
Deletions In Cwh43 Cause Idiopathic Normal Pressure Hydrocephalus,
2021
University of Massachusetts Medical School
Deletions In Cwh43 Cause Idiopathic Normal Pressure Hydrocephalus, Hong Wei Yang, Dejun Yang, Huijun Dai, Yan Zhang, Sijun Zhao, Shuo Zhang, Yan Ma, George Wang, Shaokuan Zheng, Rona S. Carroll, Mark D. Johnson
Radiology Publications
Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared ...
