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Dipeptide Repeat Proteins Inhibit Homology-Directed Dna Double Strand Break Repair In C9orf72 Als/Ftd, Nadja S. Andrade, Abbas Abdallah, Christian Mueller, Zane Zeier 2020 University of Miami

Dipeptide Repeat Proteins Inhibit Homology-Directed Dna Double Strand Break Repair In C9orf72 Als/Ftd, Nadja S. Andrade, Abbas Abdallah, Christian Mueller, Zane Zeier

Open Access Articles

BACKGROUND: The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. The C9ORF72 expansion encodes five dipeptide repeat proteins (DPRs) that are produced through a non-canonical translation mechanism. Among the DPRs, proline-arginine (PR), glycine-arginine (GR), and glycine-alanine (GA) are the most neurotoxic and increase the frequency of DNA double strand breaks (DSBs). While the accumulation of these genotoxic lesions is increasingly recognized as a feature of disease, the mechanism(s) of DPR-mediated DNA damage are ill-defined and the effect of DPRs on the efficiency ...


Antagonistic Regulation Of Circadian Output And Synaptic Development By Jetlag And The Dyschronic-Slowpoke Complex, Angelique Lamaze, James E.C. Jepson, Oghenerukevwe Akpoghiran, Kyunghee Koh 2020 Thomas Jefferson University

Antagonistic Regulation Of Circadian Output And Synaptic Development By Jetlag And The Dyschronic-Slowpoke Complex, Angelique Lamaze, James E.C. Jepson, Oghenerukevwe Akpoghiran, Kyunghee Koh

Department of Neurosciences Faculty Papers

Circadian output genes act downstream of the clock to promote rhythmic changes in behavior and physiology, yet their molecular and cellular functions are not well understood. Here we characterize an interaction between regulators of circadian entrainment, output, and synaptic development in Drosophila that influences clock-driven anticipatory increases in morning and evening activity. We previously showed the JETLAG (JET) E3 ubiquitin ligase resets the clock upon light exposure, whereas the PDZ protein DYSCHRONIC (DYSC) regulates circadian locomotor output and synaptic development. Surprisingly, we find that JET and DYSC antagonistically regulate synaptic development at the larval neuromuscular junction, and reduced JET activity ...


A Chromosomal Connectome For Psychiatric And Metabolic Risk Variants In Adult Dopaminergic Neurons, Sergio Espeso-Gil, Tyler M. Borrman, Zhiping Weng, Schahram Akbarian 2020 Icahn School of Medicine at Mount Sinai

A Chromosomal Connectome For Psychiatric And Metabolic Risk Variants In Adult Dopaminergic Neurons, Sergio Espeso-Gil, Tyler M. Borrman, Zhiping Weng, Schahram Akbarian

Open Access Articles

BACKGROUND: Midbrain dopaminergic neurons (MDN) represent 0.0005% of the brain's neuronal population and mediate cognition, food intake, and metabolism. MDN are also posited to underlay the neurobiological dysfunction of schizophrenia (SCZ), a severe neuropsychiatric disorder that is characterized by psychosis as well as multifactorial medical co-morbidities, including metabolic disease, contributing to markedly increased morbidity and mortality. Paradoxically, however, the genetic risk sequences of psychosis and traits associated with metabolic disease, such as body mass, show very limited overlap.

METHODS: We investigated the genomic interaction of SCZ with medical conditions and traits, including body mass index (BMI), by exploring ...


A Re-Evaluation Of Silk Measurement By The Cecropia Caterpillar (Hyalophora Cecropia) During Cocoon Construction Reveals Use Of A Silk Odometer That Is Temporally Regulated, Hana Sehadova, Patrick A. Guerra, Ivo Sauman, Steven M. Reppert 2020 University of South Bohemia

A Re-Evaluation Of Silk Measurement By The Cecropia Caterpillar (Hyalophora Cecropia) During Cocoon Construction Reveals Use Of A Silk Odometer That Is Temporally Regulated, Hana Sehadova, Patrick A. Guerra, Ivo Sauman, Steven M. Reppert

Open Access Articles

The late 5th instar caterpillar of the cecropia silk moth (Hyalophora cecropia) spins a silken cocoon with a distinct, multilayered architecture. The cocoon construction program, first described by the seminal work of Van der Kloot and Williams, consists of a highly ordered sequence of events. We perform behavioral experiments to re-evaluate the original cecropia work, which hypothesized that the length of silk that passes through the spinneret controls the orderly execution of each of the discrete events of cocoon spinning. We confirm and extend by three-dimensional scanning and quantitative measurements of silk weights that if cocoon construction is interrupted, upon ...


Carbon Dioxide Attracts Nesting Behavior In Captive African Naked Mole-Rats, Dan McCloskey 2020 CUNY College of Staten Island

Carbon Dioxide Attracts Nesting Behavior In Captive African Naked Mole-Rats, Dan Mccloskey

Publications and Research

This dataset contains raw Radio Frequency Identification data for a 185 hour gas infusion study conducted in the TT-2 colony at the College of Staten Island in May-June 2019. The purpose of this experiment was to determine whether colony members would be attracted to a chamber with elevated carbon dioxide levels matching the highest values recorded in the typical colony nest. The results show a significant attraction to the CO2-infused chamber during and after the period of CO2 in=fusion, with the relocation of the colony nest to this site for the first time in the history of this colony ...


B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe 2020 University of Iowa

B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe

Neurology Faculty Publications

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including ...


Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin CJ Nixon 2020 The University of Western Ontario

Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon

Electronic Thesis and Dissertation Repository

Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming ...


Transcriptomics Of Gabra4 Knockout Mice Reveals Common Nmdar Pathways Underlying Autism, Memory, And Epilepsy, Cuixia Fan, Yue Gao, Guanmei Liang, Lang Huang, Jing Wang, Xiaoxue Yang, Yiwu Shi, Ursula C. Drager, Mei Zhong, Tian-Ming Gao, Xinping Yang 2020 Southern Medical University

Transcriptomics Of Gabra4 Knockout Mice Reveals Common Nmdar Pathways Underlying Autism, Memory, And Epilepsy, Cuixia Fan, Yue Gao, Guanmei Liang, Lang Huang, Jing Wang, Xiaoxue Yang, Yiwu Shi, Ursula C. Drager, Mei Zhong, Tian-Ming Gao, Xinping Yang

Open Access Articles

Autism spectrum disorder (ASD) is a neuronal developmental disorder with impaired social interaction and communication, often with abnormal intelligence and comorbidity with epilepsy. Disturbances in synaptic transmission, including the GABAergic, glutamatergic, and serotonergic systems, are known to be involved in the pathogenesis of this disorder, yet we do not know if there is a common molecular mechanism. As mutations in the GABAergic receptor subunit gene GABRA4 are reported in patients with ASD, we eliminated the Gabra4 gene in mice and found that the Gabra4 knockout mice showed autistic-like behavior, enhanced spatial memory, and attenuated susceptibility to pentylenetetrazol-induced seizures, a constellation ...


Loss Of Huntingtin Function Slows Synaptic Vesicle Endocytosis In Striatal Neurons From The Htt(Q140/Q140) Mouse Model Of Huntington's Disease, Robyn L. McAdam, Andrew Morton, Sarah L. Gordon, Julia F. Alterman, Anastasia Khvorova, Michael A. Cousin, Karen J. Smillie 2020 University of Edinburgh

Loss Of Huntingtin Function Slows Synaptic Vesicle Endocytosis In Striatal Neurons From The Htt(Q140/Q140) Mouse Model Of Huntington's Disease, Robyn L. Mcadam, Andrew Morton, Sarah L. Gordon, Julia F. Alterman, Anastasia Khvorova, Michael A. Cousin, Karen J. Smillie

Open Access Articles

Huntington's disease (HD) is caused by CAG repeat expansion within the HTT gene, with the dysfunction and eventual loss of striatal medium spiny neurons a notable feature. Since medium spiny neurons receive high amounts of synaptic input, we hypothesised that this vulnerability originates from an inability to sustain presynaptic performance during intense neuronal activity. To test this hypothesis, primary cultures of either hippocampal or striatal neurons were prepared from either wild-type mice or a knock-in HD mouse model which contains 140 poly-glutamine repeats in the huntingtin protein (htt(Q140/Q140)). We identified a striatum-specific defect in synaptic vesicle (SV ...


Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave 2020 The Graduate Center, City University of New York

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

All Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- ...


Blocking Visual Awareness With Continuous Flash Suppression Prevents Cognitive Control, Jonathan LoVoi 2020 The Graduate Center, City University of New York

Blocking Visual Awareness With Continuous Flash Suppression Prevents Cognitive Control, Jonathan Lovoi

All Dissertations, Theses, and Capstone Projects

Cognitive control refers to a set of functions that allow for the execution of goal-directed behavior while remaining flexible to changes in task demands. Findings addressing whether or not awareness is necessary to elicit cognitive control are inconsistent, possibly stemming from the short stimulus presentation times employed in most masking paradigms, which could prevent sufficient processing time in some cases or provide a gist of the masked stimulus in other cases. The present study examined the necessity of awareness in cognitive control using Continuous Flash Suppression (CFS) to suppress stimulus awareness for periods of time longer than possible with other ...


Tamalin/Gras-1 Connects Glutamate Receptor Activity To The Insulin/Igf Signaling Cascade To Regulate Neuroprotection In A Nematode Model Of Excitotoxicity, Ayesha Chowdhury 2020 The Graduate Center, City University of New York

Tamalin/Gras-1 Connects Glutamate Receptor Activity To The Insulin/Igf Signaling Cascade To Regulate Neuroprotection In A Nematode Model Of Excitotoxicity, Ayesha Chowdhury

All Dissertations, Theses, and Capstone Projects

Brain ischemia is a major cause of debilitation and death in the United States. Excitotoxicity, a condition that arises from the accumulation of glutamate (Glu) in the synapse that leads to overactivation of Glu receptors (GluRs), is the major mechanism of neuronal damage in brain ischemia / stroke. Although it is commonly acknowledged that over activation of GluRs leads to neurodegeneration, it has been recently shown that even during excitotoxicity Glu has a concurrent important role in regulating neuroprotection. GluR-activated transcription factors seem to mediate this neuroprotection, but it remains unclear which signaling cascades and transcription factors are regulated by GluRs ...


Experience-Dependent Changes In Nucleus Accumbens Activity Predict Cued Approach Learning: Contribution Of Nmda Receptors, Mercedes Vega Villar 2020 The Graduate Center, City University of New York

Experience-Dependent Changes In Nucleus Accumbens Activity Predict Cued Approach Learning: Contribution Of Nmda Receptors, Mercedes Vega Villar

All Dissertations, Theses, and Capstone Projects

Animals learn associations between environmental cues and the natural rewards they predict (e.g., food, water, sex). As a result, reward-predictive cues come to trigger vigorous reward-seeking responses. Many neurons in the nucleus accumbens (NAc) become excited upon presentation of an already-learned reward-predictive cue. These NAc responses encode the motivational value of the cue and are necessary for the expression of the subsequent approach behavior. However, the precise temporal relationship between the emergence of cue-evoked excitations in the NAc and the acquisition of cued approach behavior remains unknown. In Experiment 1, NAc activity was recorded as rats learned to approach ...


Using An Internal Auditory Stimulus To Activate The Developing Primary Auditory Cortex: A Fetal Fmri Study, Estee Goldberg 2020 The University of Western Ontario

Using An Internal Auditory Stimulus To Activate The Developing Primary Auditory Cortex: A Fetal Fmri Study, Estee Goldberg

Electronic Thesis and Dissertation Repository

Insight into the rapidly developing brain in utero is scarce. Fetal functional magnetic resonance imaging (fMRI) is a technique used to gain awareness into the developmental process. Previous auditory task-based fMRI studies employed an external sound stimulus directly on the maternal abdomen. However, there has since been recommendation to cease doing so. We sought to investigate a reliable paradigm to study the development of fetal brain networks and postulate that by using an internal stimulus, such as the mother singing, it would result in activation of the fetal primary auditory cortex. Volunteers carrying singleton fetuses with a gestational age of ...


Integrated Mirna-/Mrna-Seq Of The Habenulo-Interpeduncular Circuit During Acute Nicotine Withdrawal, Alison P. Casserly, Junko Tsuji, Rubing Zhao-Shea, Ciearra B. Smith, Susanna Molas-Casacuberta, Andrew R. Tapper, Zhiping Weng, Paul D. Gardner 2020 University of Massachusetts Medical School

Integrated Mirna-/Mrna-Seq Of The Habenulo-Interpeduncular Circuit During Acute Nicotine Withdrawal, Alison P. Casserly, Junko Tsuji, Rubing Zhao-Shea, Ciearra B. Smith, Susanna Molas-Casacuberta, Andrew R. Tapper, Zhiping Weng, Paul D. Gardner

Open Access Articles

Tobacco use is the leading preventable cause of mortality in the world. The limited number of smoking cessation aids currently available are minimally effective, highlighting the need for novel therapeutic interventions. We describe a genome-wide approach to identify potential candidates for such interventions. Next-generation sequencing was performed using RNA isolated from the habenulo-interpeduncular circuit of male mice withdrawn from chronic nicotine treatment. This circuit plays a central role in the nicotine withdrawal response. Differentially expressed miRNAs and mRNAs were validated using RT-qPCR. Many of the differentially expressed mRNAs are predicted targets of reciprocally expressed miRNAs. We illustrate the utility of ...


Toward A Neurological Understanding Of Metacognition, Philip Hulbig 2020 Lesley University

Toward A Neurological Understanding Of Metacognition, Philip Hulbig

Educational Studies Dissertations

Metacognitive interventions have been shown to be tremendously important to general education and supporting individuals with neurological disabilities (Brown, 1978; Webb, 1989; Dunlosky & Metcalfe, 2009; Dweck, 2017). This paper details the many facets and relationships between neurology and metacognition. The investigation draws from a wide diversity of neuro-investigational techniques and findings related to metacognition, executive function, self-reflection, self-evaluation, self-development and self-directed learning. It ends with a discussion of common threads and themes drawn from the research, and how methodological definitions for metacognitive knowledge and metacognitive regulation can be combined with physiologically-focused neurobiological approaches and consciousness-focused psychological approaches to broaden understanding and further ...


Modeling Conventionalization And Predictability Within Mwes At The Brain Level, Shohini Bhattasali, Murielle Popa-Fabre, Christophe Pallier, John Hale 2020 University of Maryland, College Park

Modeling Conventionalization And Predictability Within Mwes At The Brain Level, Shohini Bhattasali, Murielle Popa-Fabre, Christophe Pallier, John Hale

Proceedings of the Society for Computation in Linguistics

While expressions have traditionally been binarized as compositional and noncompositional in linguistic theory, Multiword Expressions (MWEs) demonstrate finer-grained distinctions. Using Association Measures like Pointwise Mutual Information and Dice's Coefficient, MWEs can be characterized as having different degrees of conventionalization and predictability. Our goal is to investigate how these gradiences could reflect cognitive processes. In this study, fMRI recordings of naturalistic narrative comprehension is used to probe to what extent these computational measures and the cognitive processes they could operationalize are observable during on-line sentence processing. Our results show that Dice's Coefficent, representing lexical predictability, is a better predictor ...


Implicit Bias Through The Lens Of Electroencephalography, Hope Cooper 2020 Connecticut College

Implicit Bias Through The Lens Of Electroencephalography, Hope Cooper

Behavioral Neuroscience Honors Papers

Unconscious or implicit bias is a part of everyday life. All human beings both exhibit implicit bias and (some more than others) are also the victims of it. Due to the way humans have evolved implicit bias will never be something that ceases to exist. Thus, it is important that neuroscience and social science closely study how it works and how to curb the behaviors caused by implicit bias. In the following research EEG (electroencephalography) was used alongside a weapons IAT (Implicit Association Test) to examine specific neural components that may correlate with higher bias scores on the IAT. Specific ...


Epigenetic Alterations At Synaptic Plasticity Genes In A Genetically Heterogeneous Rat Model Of Neuropsychiatric Disorders, Doan M. On 2020 Virginia Commonwealth University

Epigenetic Alterations At Synaptic Plasticity Genes In A Genetically Heterogeneous Rat Model Of Neuropsychiatric Disorders, Doan M. On

Theses and Dissertations

Sensorimotor gating impairments are observed across a range of neuropsychiatric conditions. The prepulse inhibition of the acoustic startle response (PPI) is a validated measure of sensorimotor gating. Genetic and pharmacological manipulations in rodents have shown PPI is regulated by specific brain monoaminergic systems. Using genetically heterogeneous NIH-HS rats, we stratified individuals by %PPI. In low PPI animals, we observed elevated mRNA levels of certain neurotransmitter receptors, including metabotropic glutamate receptor Grm2, dopamine receptors Drd1 and Drd2, serotonin receptors Htr1a and Htr2a, and scaffolding protein Homer1, in the frontal cortex (FC) and striatum (STR). We found Drd2 mRNA levels were significantly ...


A Genome-Wide Association Study Of Cocaine Use Disorder Accounting For Phenotypic Heterogeneity And Gene–Environment Interaction, Jiangwen Sun, Henry R. Kranzler, Joel Gelernter, Jinbo Bi 2020 Old Dominion University

A Genome-Wide Association Study Of Cocaine Use Disorder Accounting For Phenotypic Heterogeneity And Gene–Environment Interaction, Jiangwen Sun, Henry R. Kranzler, Joel Gelernter, Jinbo Bi

Computer Science Faculty Publications

Background: Phenotypic heterogeneity and complicated gene-environment interplay in etiology are among the primary factors that hinder the identification of genetic variants associated with cocaine use disorder. Methods: To detect novel genetic variants associated with cocaine use disorder, we derived disease traits with reduced phenotypic heterogeneity using cluster analysis of a study sample (n = 9965). We then used these traits in genome-wide association tests, performed separately for 2070 African Americans and 1570 European Americans, using a new mixed model that accounted for the moderating effects of 5 childhood environmental factors. We used an independent sample (918 African Americans, 1382 European Americans ...


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