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Production Of Poly(Ga) In C9orf72 Patient Motor Neurons Derived From Induced Pluripotent Stem Cells, Sandra Almeida, Gopinath Krishnan, Mia Rushe, Yuanzheng Gu, Mark W. Kankel, Fen-Biao Gao 2019 University of Massachusetts Medical School

Production Of Poly(Ga) In C9orf72 Patient Motor Neurons Derived From Induced Pluripotent Stem Cells, Sandra Almeida, Gopinath Krishnan, Mia Rushe, Yuanzheng Gu, Mark W. Kankel, Fen-Biao Gao

Open Access Articles

GGGGCC (G4C2) repeat expansion in the first intron of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A key pathological hallmark of C9ORF72-related ALS/FTD is the accumulation of dipeptide repeat (DPR) proteins synthesized from both sense and antisense repeat RNAs in affected neurons.To investigate how DPR proteins are synthesized in C9ORF72 human neurons, we used CRISPR-Cas9 technology to generate a homozygous deletion in the first intron of C9ORF72, 5′ to the G4C2 repeats to assess the effect of this deletion on DPR production.


The Influence Of Neural Reward Processing On Memory In Depression, Nathan M. Hager 2019 Old Dominion University

The Influence Of Neural Reward Processing On Memory In Depression, Nathan M. Hager

Psychology Theses & Dissertations

Theories and research suggest that depression involves impaired reward sensitivity and a deficit in memory for rewarding stimuli. Some researchers propose that this memory deficit may result from reduced neural reward sensitivity, which impairs the encoding of reward-related memories, but few studies have directly probed this connection. Such research may benefit from examining the reward positivity (RewP), an event-related potential (ERP) previously linked to reduced reward sensitivity in depression. Undergraduates with high or low self-reported depression completed a task in which they chose one of three doors, revealing a neutral word written in a color which indicated an outcome of ...


Viscoelastic Properties Of Shock Wave Exposed Brain Tissue Subjected To Unconfined Compression Experiments, Annastacia K. McCarty, Ling Zhang, Sarah Hansen, William J. Jackson, Sarah A. Bentil 2019 Iowa State University

Viscoelastic Properties Of Shock Wave Exposed Brain Tissue Subjected To Unconfined Compression Experiments, Annastacia K. Mccarty, Ling Zhang, Sarah Hansen, William J. Jackson, Sarah A. Bentil

Mechanical Engineering Publications

Traumatic brain injuries (TBI) affect millions of people each year. While research has been dedicated to determining the mechanical properties of the uninjured brain, there has been a lack of investigation on the mechanical properties of the brain after experiencing a primary blast-induced TBI. In this paper, whole porcine brains were exposed to a shock wave to simulate blast-induced TBI. First, ten (10) brains were subjected to unconfined compression experiments immediately following shock wave exposure. In addition, 22 brains exposed to a shock wave were placed in saline solution and refrigerated between 30 minutes and 6.0 hours before undergoing ...


Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes 2019 University of Tennessee, Knoxville

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.


In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins 2019 Stanford University

In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins

Open Access Articles

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two ...


Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei 2019 University of Nevada, Las Vegas

Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei

School of Medicine Faculty Publications

Genome-wide association studies (GWAS) have identified over 100 loci associated with schizophrenia. Most of these studies test genetic variants for association one at a time. In this study, we performed GWAS of the molecular genetics of schizophrenia (MGS) dataset with 5334 subjects using multivariate Bayesian variable selection (BVS) method Posterior Inference via Model Averaging and Subset Selection (piMASS) and compared our results with the previous univariate analysis of the MGS dataset. We showed that piMASS can improve the power of detecting schizophrenia-associated SNPs, potentially leading to new discoveries from existing data without increasing the sample size. We tested SNPs in ...


Non-Equilibrium Critical Dynamics Of Bursts In Theta And Delta Rhythms As Fundamental Characteristic Of Sleep And Wake Micro-Architecture, Jilin W. J. L. Wang, Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, Plamen Ch. Ivanov 2019 Boston University

Non-Equilibrium Critical Dynamics Of Bursts In Theta And Delta Rhythms As Fundamental Characteristic Of Sleep And Wake Micro-Architecture, Jilin W. J. L. Wang, Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, Plamen Ch. Ivanov

Open Access Articles

Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate theta and delta wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in theta and delta rhythms exhibit a complex temporal organization, with long-range power-law correlations and ...


Introduction To The Special Issue On Reproducibility In Neuroimaging, Russell A. Poldrack, Kirstie Whitaker, David N. Kennedy 2019 Stanford University

Introduction To The Special Issue On Reproducibility In Neuroimaging, Russell A. Poldrack, Kirstie Whitaker, David N. Kennedy

Open Access Articles

The last decade has seen increasing attention to the problem of scientific reproducibility, across a broad range of scientific fields (Camerer et al., 2016;Morrison, 2014;Open Science Collaboration, 2015). Within the field of neuroimaging, there has been a particular focus on issues of analytic variability (Bowring et al., 2019;Carp, 2012) statistical power (Button et al., 2013;Poldrack et al., 2017), and test-retest reliability (Bennett and Miller, 2013), all of which have raised alarms regarding the potential for irreproducible results. In addition, failed replications (Boekel et al., 2015;Dinga et al., 2019) and meta-analytic null results (Müller et al ...


Executive Dysfunction Following A Sport-Related Concussion Is Independent Of Task-Based Symptom Burden, Naila Ayala Angumba 2019 The University of Western Ontario

Executive Dysfunction Following A Sport-Related Concussion Is Independent Of Task-Based Symptom Burden, Naila Ayala Angumba

Electronic Thesis and Dissertation Repository

The present work examined whether oculomotor deficits associated with a sport-related concussion (SRC) reflect an impairment to executive-based planning mechanisms or a task-based increase in concussion symptomology (e.g., headache, vertigo). Therefore, I employed a standardized measure of SRC symptom severity (SCAT-5), antisaccade performance and pupillometry metrics in persons with a SRC during early (i.e., initial assessment: ≤12 days post-SRC) and later (i.e., follow-up assessment: 14-30 days post-SRC) stages of recovery. In the initial assessment, the SRC group yielded longer reaction times (RT) (p=0.001), increased directional errors (p=0.002) and larger task-evoked pupil dilations (TEPD ...


Drosophila Psi Controls Circadian Period And The Phase Of Circadian Behavior Under Temperature Cycle Via Tim Splicing, Lauren E. Foley, Jinli Ling, Radhika Sudhir Joshi, Naveh Evantal, Sebastian Kadener, Patrick Emery 2019 University of Massachusetts Medical School

Drosophila Psi Controls Circadian Period And The Phase Of Circadian Behavior Under Temperature Cycle Via Tim Splicing, Lauren E. Foley, Jinli Ling, Radhika Sudhir Joshi, Naveh Evantal, Sebastian Kadener, Patrick Emery

Open Access Articles

The Drosophila circadian pacemaker consists of transcriptional feedback loops subjected to post-transcriptional and post-translational regulation. While post-translational regulatory mechanisms have been studied in detail, much less is known about circadian post-transcriptional control. Thus, we targeted 364 RNA binding and RNA associated proteins with RNA interference. Among the 43 hits we identified was the alternative splicing regulator P-element somatic inhibitor (PSI). PSI regulates the thermosensitive alternative splicing of timeless (tim), promoting splicing events favored at warm temperature over those increased at cold temperature. Psi downregulation shortens the period of circadian rhythms and advances the phase of circadian behavior under temperature cycle ...


Free Circular Introns With An Unusual Branchpoint In Neuronal Projections, Harleen Saini, Alicia A. Bicknell, Sean R. Eddy, Melissa J. Moore 2019 University of Massachusetts Medical School

Free Circular Introns With An Unusual Branchpoint In Neuronal Projections, Harleen Saini, Alicia A. Bicknell, Sean R. Eddy, Melissa J. Moore

Open Access Articles

The polarized structure of axons and dendrites in neuronal cells depends in part on RNA localization. Previous studies have looked at which polyadenylated RNAs are enriched in neuronal projections or at synapses, but less is known about the distribution of non-adenylated RNAs. By physically dissecting projections from cell bodies of primary rat hippocampal neurons and sequencing total RNA, we found an unexpected set of free circular introns with a non-canonical branchpoint enriched in neuronal projections. These introns appear to be tailless lariats that escape debranching. They lack ribosome occupancy, sequence conservation, and known localization signals, and their function, if any ...


Reassessing The Role Of Histaminergic Tuberomammillary Neurons In Arousal Control, Anne Venner, Takatoshi Mochizuki, Roberto De Luca, Christelle Anaclet, Thomas E. Scammell, Clifford B. Saper, Elda Arrigoni, Patrick M. Fuller 2019 Harvard Medical School

Reassessing The Role Of Histaminergic Tuberomammillary Neurons In Arousal Control, Anne Venner, Takatoshi Mochizuki, Roberto De Luca, Christelle Anaclet, Thomas E. Scammell, Clifford B. Saper, Elda Arrigoni, Patrick M. Fuller

Neurobiology Publications

The histaminergic neurons of the tuberomammillary nucleus (TMN(HDC)) of the posterior hypothalamus have long been implicated in promoting arousal. More recently, a role for GABAergic signaling by the TMN(HDC) neurons in arousal control has been proposed. Here, we investigated the effects of selective chronic disruption of GABA synthesis (via genetic deletion of the GABA synthesis enzyme, glutamic acid decarboxylase 67) or GABAergic transmission (via genetic deletion of the vesicular GABA transporter (VGAT)) in the TMN(HDC) neurons on sleep-wake in male mice. We also examined the effects of acute chemogenetic activation and optogenetic inhibition of TMN(HDC) neurons ...


#44 - Effects Of Chemical Vagotomy On The Neonatal Mouse Paraventricular Nucleus Of The Hypothalamus, Aviva Gars, Alexandra Castillo-Ruiz, Benoit Chassaing, Nancy Forger 2019 Georgia State University

#44 - Effects Of Chemical Vagotomy On The Neonatal Mouse Paraventricular Nucleus Of The Hypothalamus, Aviva Gars, Alexandra Castillo-Ruiz, Benoit Chassaing, Nancy Forger

Georgia Undergraduate Research Conference (GURC)

Birth is marked by a dramatic transition from the sterile womb to a world full of microorganisms that colonize every body surface. We previously found that this colonization exerts rapid effects on brain development, as in mice born in the absence of microbes had increased cell death in the paraventricular nucleus of the hypothalamus (PVN), an effect not seen 12 h prior to expected delivery. The gut microbiota influences the development of many body systems, and communicates bi-directionally with the brain. We hypothesize that the microbiota exerts effects on neuronal cell death via the vagus nerve, which connects the gut ...


#7 - The Role Of Rnf216/Triad3 In Neuroinflammation Through Interactions With Toll-Like-Receptors, Dustin Grossman 2019 Georgia State University

#7 - The Role Of Rnf216/Triad3 In Neuroinflammation Through Interactions With Toll-Like-Receptors, Dustin Grossman

Georgia Undergraduate Research Conference (GURC)

Ubiquitin E3 ligases are enzymes that mark certain substrates with ubiquitin proteins which leads to different cellular fates. Ring finger protein 216 (RNF216) is a ubiquitin E3 ligase that is involved in synaptic plasticity, inhibiting cellular autophagy, and the immune response in the peripheral nervous system. Previous literature has demonstrated that RNF216 participates in various aspects of inflammation by regulating ubiquitination and proteasomal degradation of receptor-interacting serine-threonine kinase 1 (RIPK1), toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), and TIR-domain-containing adapter-inducing interferon-β (TRIF), targeting TNF receptor associated factor 3 (TRAF3) for degradation. TLRs initiate signal transduction pathways which can lead ...


#45 - The Ancient Origins Of Trp-Dependent Menthol Sensing, Maggie Benson 2019 Georgia State University

#45 - The Ancient Origins Of Trp-Dependent Menthol Sensing, Maggie Benson

Georgia Undergraduate Research Conference (GURC)

Authors: Maggie N. Benson, Nathaniel J. Himmel, Jamin M. Letcher, Akira Sakurai, Thomas R. Gray, and Daniel N. Cox

Author emails: nhimmel1@student.gsu.edu, jletcher@student.gsu.edu, akira@gsu.edu, tgray18@gsu.edu, dcox18@gsu.edu

In humans, topical application of menthol typically elicits a pleasant cooling sensation. Insects like Drosophila melanogaster, however, find menthol aversive. In chordates, the primary molecular sensors of menthol are the transient receptor potential (TRP) channels TRPA1 and TRPM8. TRP channels are highly conserved, incredibly ancient, and important in sensing both noxious and innocuous stimuli – importantly, they are key to systems underlying nociception ...


#4 - Endosomal Proteins In Neurodevelopmental Disorders, Ruvimbo Dzvurumi, Jhodi Webster, Jennifer Larimore Dr, Lauren Neal, Rachel Thompson, Alex Lombardo, Camryn Smith, Sami Hatcher 2019 Agnes Scott College

#4 - Endosomal Proteins In Neurodevelopmental Disorders, Ruvimbo Dzvurumi, Jhodi Webster, Jennifer Larimore Dr, Lauren Neal, Rachel Thompson, Alex Lombardo, Camryn Smith, Sami Hatcher

Georgia Undergraduate Research Conference (GURC)

Rett Syndrome is a neurodevelopmental disorder that primarily affects females and is detected at 6-18 months of age. Rett Syndrome results from a mutations in the methyl-CpG binding protein 2 gene (MECP2) which is found on the X chromosome. Its mutation results in impairment in cognitive, sensory, emotional, motor and autonomic functions. Schizophrenia is also a neurodevelopmental disorder with onset in adulthood, however there is no single genetic cause. Endosomal proteins have been implicated in both disorders through GWAS studies and animal models, suggesting a common molecular mechanism shared between these neurodevelopmental disorders. Previous research in our lab has demonstrated ...


#17 - Glia Characterization In Bloc-1 Deficient Mice, Jhodi Webster, Jennifer Larimore 2019 Agnes Scott College

#17 - Glia Characterization In Bloc-1 Deficient Mice, Jhodi Webster, Jennifer Larimore

Georgia Undergraduate Research Conference (GURC)

Schizophrenia (SZ) is a chronic mental disorder characterized by hallucinations, disorganized speech, memory deficits and an emotionless demeanor. It has been reported that dysbindin, a subunit of the octomeric BLOC-1 complex, is reduced in the hippocampus of patients with SZ. Dysbindin regulates endosomal trafficking and has also been localized to the astroglial endfeet and endothelial cells that line capillaries in the cerebellum. Microglial activation has been implicated in neurological disorders and may regulate SZ progression. Thus, further characterization of glia cell function in SZ is necessary. This study will examine glia cell markers in dysbindin deficient mice in an effort ...


#50 - Parkinson’S Disease And Task Switching: Effects Of Varying The Frequency Of Deep Brain Stimulation In The Subthalamic Nucleus, Ta-Tyonna Buck, Rachel Cole 2019 Georgia Southern University

#50 - Parkinson’S Disease And Task Switching: Effects Of Varying The Frequency Of Deep Brain Stimulation In The Subthalamic Nucleus, Ta-Tyonna Buck, Rachel Cole

Georgia Undergraduate Research Conference (GURC)

Managing multiple cognitive tasks at once incurs a “switch cost”, measured as slower responses and increased errors when switching between tasks. This switch cost is greater in individuals with Parkinson’s Disease (PD). Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is an effective treatment for motor symptoms in PD patients; however, high frequency STN-DBS in the motor region often leads to worsening cognitive control. Studies suggest that oscillations at low frequencies (2-7 Hz) across brain circuits support cognition, yet little work has been done on the cognitive effects of different DBS frequencies. We predicted that PD patients would ...


A Multi-Approach Investigation To Evaluate Compounds That Mitigate Neuroinflammation., Gabriella Hernandez-Tyler 2019 Georgia Gwinnett College

A Multi-Approach Investigation To Evaluate Compounds That Mitigate Neuroinflammation., Gabriella Hernandez-Tyler

Georgia Undergraduate Research Conference (GURC)

Parkinson’s disease is a progressive neurodegenerative disorder, which affects the basal ganglia and the activity of dopamine, a neurotransmitter in the brain. This interruption of dopamine appears to provide an explanation as to the loss of motor function by those who have Parkinson’s disease (PD). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prodrug to MPP+, a known neurotoxin which induces Parkinsonian symptoms to those exposed to it. The goal of this study was to: 1) to investigate the potential for nicotine and velvet bean extract to protect against MPTP-induced neurotoxicity and 2) to establish a zebrafish (Danio rerio ...


Function And Dissipation In Finite State Automata - From Computing To Intelligence And Back, Natesh Ganesh 2019 University of Massachusetts Amherst

Function And Dissipation In Finite State Automata - From Computing To Intelligence And Back, Natesh Ganesh

Doctoral Dissertations

Society has benefited from the technological revolution and the tremendous growth in computing powered by Moore's law. However, we are fast approaching the ultimate physical limits in terms of both device sizes and the associated energy dissipation. It is important to characterize these limits in a physically grounded and implementation-agnostic manner, in order to capture the fundamental energy dissipation costs associated with performing computing operations with classical information in nano-scale quantum systems. It is also necessary to identify and understand the effect of quantum in-distinguishability, noise, and device variability on these dissipation limits. Identifying these parameters is crucial to ...


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