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Single-Base Resolution Mapping Of 5-Hydroxymethylcytosine Modifications In Hippocampus Of Alzheimer's Disease Subjects, Elizabeth M. Ellison, Melissa A. Bradley-Whitman, Mark A. Lovell 2017 University of Kentucky

Single-Base Resolution Mapping Of 5-Hydroxymethylcytosine Modifications In Hippocampus Of Alzheimer's Disease Subjects, Elizabeth M. Ellison, Melissa A. Bradley-Whitman, Mark A. Lovell

Chemistry Faculty Publications

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects ...


Regulation Of The Amyloid Precursor Protein By Prostaglandin J2, A Mediator Of Inflammation: Relevance To Alzheimer’S Disease, Teneka L. Jean-Louis 2017 The Graduate Center, City University of New York

Regulation Of The Amyloid Precursor Protein By Prostaglandin J2, A Mediator Of Inflammation: Relevance To Alzheimer’S Disease, Teneka L. Jean-Louis

All Dissertations, Theses, and Capstone Projects

Inflammation plays a major role in Alzheimer’s disease (AD). Investigating how specific mediators of inflammation contribute to neurodegeneration in AD is crucial. Our studies focused on cyclooxygenases, which are key enzymes in inflammation and highly relevant to AD. Cyclooxygenases (COX -1, constitutive; COX-2, inducible) have emerged as important determinants of AD pathogenesis and progression. COX-2 is highly induced in AD, correlating with AD severity, and COX-1 is also involved in AD. Cyclooxygenases are the rate-limiting enzymes that convert arachidonic acid into prostaglandins (PGs), the principal mediators of CNS neuroinflammation.

The overall GOAL of these studies was to address the ...


The Dopamine Transporter Recycles Via A Retromer-Dependent Postendocytic Mechanism: Tracking Studies Using A Novel Fluorophore-Coupling Approach, Sijia Wu, Rita R. Fagan, Chayasith Uttamapinant, Lawrence M. Lifshitz, Kevin E. Fogarty, Alice Y. Ting, Haley Melikian 2017 University of Massachusetts Medical School

The Dopamine Transporter Recycles Via A Retromer-Dependent Postendocytic Mechanism: Tracking Studies Using A Novel Fluorophore-Coupling Approach, Sijia Wu, Rita R. Fagan, Chayasith Uttamapinant, Lawrence M. Lifshitz, Kevin E. Fogarty, Alice Y. Ting, Haley Melikian

University of Massachusetts Medical School Faculty Publications

Presynaptic reuptake, mediated by the dopamine (DA) transporter (DAT), terminates DAergic neurotransmission and constrains extracellular DA levels. Addictive and therapeutic psychostimulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neuropsychiatric disorders. These findings underscore that DAT is critical for DA neurotransmission and homeostasis. DAT surface availability is regulated acutely by endocytic trafficking, and considerable effort has been directed toward understanding mechanisms that govern DAT's plasma membrane expression and postendocytic fate. Multiple studies have demonstrated DAT endocytic recycling and enhanced surface delivery in response to various stimuli. Paradoxically, imaging studies have not detected DAT ...


Alterations In Mrna 3' Utr Isoform Abundance Accompany Gene Expression Changes In Human Huntington's Disease Brains, Lindsay S. Romo, Ami Ashar-Patel, Edith L. Pfister, Neil Aronin 2017 University of Massachusetts Medical School

Alterations In Mrna 3' Utr Isoform Abundance Accompany Gene Expression Changes In Human Huntington's Disease Brains, Lindsay S. Romo, Ami Ashar-Patel, Edith L. Pfister, Neil Aronin

Open Access Articles

The huntingtin gene has two mRNA isoforms that differ in their 3' UTR length. The relationship of these isoforms with Huntington's disease is not established. We provide evidence that the abundance of huntingtin 3' UTR isoforms differs between patient and control neural stem cells, fibroblasts, motor cortex, and cerebellum. Huntingtin 3' UTR isoforms, including a mid-3' UTR isoform, have different localizations, half-lives, polyA tail lengths, microRNA sites, and RNA-binding protein sites. Isoform shifts in Huntington's disease motor cortex are not limited to huntingtin; 11% of alternatively polyadenylated genes change the abundance of their 3' UTR isoforms. Altered expression ...


C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl Eggers, Noelle L’Etoile, Laura Miller Conrad, Miri VanHoven 2017 San Jose State University

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl Eggers, Noelle L’Etoile, Laura Miller Conrad, Miri Vanhoven

Faculty Publications, Chemistry

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic ...


C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen T. O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Y. Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl K. Eggers, Noelle L’Etoile, Laura C. Miller Conrad, Miri VanHoven 2017 San Jose State University

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen T. O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Y. Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl K. Eggers, Noelle L’Etoile, Laura C. Miller Conrad, Miri Vanhoven

Daryl K. Eggers

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic ...


C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen T. O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Y. Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl K. Eggers, Noelle L’Etoile, Laura C. Miller Conrad, Miri VanHoven 2017 San Jose State University

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen T. O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Y. Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl K. Eggers, Noelle L’Etoile, Laura C. Miller Conrad, Miri Vanhoven

Miri VanHoven

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic ...


Study Of Regulated Cell Death In Two Systems: Pd-1 In Natural Killer Cells And Rip3 In Neurons, YU HUANG 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Study Of Regulated Cell Death In Two Systems: Pd-1 In Natural Killer Cells And Rip3 In Neurons, Yu Huang

UT GSBS Dissertations and Theses (Open Access)

Cell death is not only an essential phenomenon in normal development and homeostasis, but also crucial in various pathologies. It is now clear that many types of cell death can be regulated by pharmacological or genetic interventions. These were largely achieved by identifying the molecular mechanisms underlying the regulated cell death (RCD). While in the immune system, RCD needs to be facilitated to help the clearance of pathogens and tumors, in healthy cells, especially the terminally differentiated neurons in the nervous system, it is more desirable to protect cells from dying due to stress under pathological conditions. Thus, understating the ...


Modulation Of The Sodium/Potassium Atpase Function And Expression By Transcranial Direct Current Stimulation Of The Right Sensorimotor Cortex In Mice, Salim Bendaoud 2017 The Graduate Center, City University of New York

Modulation Of The Sodium/Potassium Atpase Function And Expression By Transcranial Direct Current Stimulation Of The Right Sensorimotor Cortex In Mice, Salim Bendaoud

All Dissertations, Theses, and Capstone Projects

Direct current stimulation is used as a noninvasive therapeutic technique to enhance motor recovery following stroke, and to improve cognitive functions. This technique also showed promising results in the treatment of depression, schizophrenia, and multiple sclerosis. Transcranial direct current stimulation has been proven to cause a polarization (depolarization or hyperpolarization) of the target tissues depending on the polarity of the current and cell orientation. Because of the induced polarization, the spontaneous activity of the neurons is further affected. With exception to this electrophysiological effect, the overall biological mechanisms of transcranial direct current stimulation on the underlying tissues remain largely unknown ...


Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael 2017 The Graduate Center, City University of New York

Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael

All Dissertations, Theses, and Capstone Projects

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present ...


Microglia In Alzheimer's Disease, Heela Sarlus, Michael T. Heneka 2017 University of Bonn

Microglia In Alzheimer's Disease, Heela Sarlus, Michael T. Heneka

Open Access Articles

Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. Microglia express a wide range of receptors that act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition to their classical immune cell function, microglia act as guardians of the brain by promoting phagocytic clearance and providing trophic support to ensure tissue repair and maintain cerebral homeostasis. Conditions associated with loss of homeostasis or tissue changes induce several dynamic microglial processes, including changes of cellular morphology, surface phenotype, secretory mediators, and proliferative responses (referred to as an "activated state ...


Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo 2017 University of Kentucky

Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in ...


Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque 2017 The University of Western Ontario

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show ...


Inflammasome Activation By Methamphetamine Potentiates Lipopolysaccharide Stimulation Of Il-1Β Production In Microglia, Enquan Xu 2017 University of Nebraska Medical Center

Inflammasome Activation By Methamphetamine Potentiates Lipopolysaccharide Stimulation Of Il-1Β Production In Microglia, Enquan Xu

Theses & Dissertations

Methamphetamine (Meth) is a psychostimulant drug that is widely abused all around the world. The administration of Meth causes a strong instant euphoria effect, and long-term of abuse is correlative of drug-dependence and neurotoxicity. The neuroimaging studies demonstrated that the long-term abuse of Meth is associated with the reduction of the dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) in the striatum. Neuroinflammation is well-accepted as an important mechanism underlying the Meth-induced neurotoxicity. The over-activated microglia were found both in Meth human abusers and animal models.

NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is the most predominant Nod-like ...


Pattern Recognition Receptors, Immune Proteins, And Nf-Κb Signaling Regulate Behaviors Associated With Aging Phenotypes, Nicholas W. DeKorver 2017 University of Nebraska Medical Center

Pattern Recognition Receptors, Immune Proteins, And Nf-Κb Signaling Regulate Behaviors Associated With Aging Phenotypes, Nicholas W. Dekorver

Theses & Dissertations

The aging process is accompanied by functional impairments, including reduced locomotor function, fragmentation of active states, and alterations in energy balance. Our lab has demonstrated that immune proteins are increased in specific regions of the mouse brain that correlate with strain specific deficits. These immune proteins include toll-like receptors (Tlr), class I major histocompatibility complex proteins (MHC I), and complement proteins. There is an increasing appreciation for the role of immune proteins in neurodevelopment; however, their involvement in age-associated deficits is poorly understood. Here, we present data demonstrating that 1) activation of a specific immune receptor (Tlr2) leads to changes ...


Modification Of Aplysia Feeding Network By L-Dopa And Dopamine-Dependent Learning, Curtis Neveu, Curtis L. Neveu 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Modification Of Aplysia Feeding Network By L-Dopa And Dopamine-Dependent Learning, Curtis Neveu, Curtis L. Neveu

UT GSBS Dissertations and Theses (Open Access)

Dopamine (DA) is a ubiquitous neuromodulator of neuronal networks in the animal kingdom and has a well-established role in modulating motor behavior and encoding reward information. Although the effects of DA and DA-dependent learning at the behavioral and molecular levels are well-understood, many questions still remain concerning the effects of DA at the network level. DA-dependent learning effects on a neuronal circuit were examined by measuring the biophysical properties before and after in vitro operant conditioning (OC) of the feeding circuit of Aplysia. OC reduced the excitability of B4 and the B4-to-B51 synaptic connection, with a trend towards an enhancement ...


Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay 2017 University of Tennessee, Knoxville

Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay

Doctoral Dissertations

Alcohol abuse induces many disorders including depression, metabolic syndrome, and sleep disturbances. The strong link between alcohol abuse and sleep problems, along with the close connection between sleep and circadian rhythms, led us to investigate ethanol’s effects on the circadian clock. Previous work has shown that acute ethanol blocks photic phase shifts in vivo and glutamatergic phase shifts in vitro. However, neural systems become tolerant to ethanol across different timeframes. Despite both ethanol tolerance and ethanol withdrawal syndrome being listed as criteria for developing alcohol use disorders, little is known about how ethanol tolerance and withdrawal induced hyperexcitability develop ...


Evolution Of Caffeine Biosynthetic Enzymes And Pathways In Flowering Plants, Ruiqi Huang 2017 Western Michigan University

Evolution Of Caffeine Biosynthetic Enzymes And Pathways In Flowering Plants, Ruiqi Huang

Dissertations

Convergent evolution generally refers to the independent evolution of similar biological function more than once in unrelated species. Caffeine is thought to have evolved by convergence, and is naturally produced through secondary metabolism in plants to defend against pathogen attack and insect feeding or to attract pollinators. The same caffeine biosynthetic pathway has been elucidated in Camellia (tea) and Coffea (coffee), in which xanthosine is sequentially methylated to caffeine via 7-methylxanthine and theobromine. However, although the same catalysis pathway is used, different (paralogous) enzymes in the SAMT/BAMT/theobromine synthase (SABATH) multigene family are used in the two species. In ...


Regulation Of Local Translation, Synaptic Plasticity, And Cognitive Function By Cnot7, Rhonda L. McFleder 2017 University of Massachusetts Medical School

Regulation Of Local Translation, Synaptic Plasticity, And Cognitive Function By Cnot7, Rhonda L. Mcfleder

GSBS Dissertations and Theses

Local translation of mRNAs in dendrites is vital for synaptic plasticity and learning and memory. Tight regulation of this translation is key to preventing neurological disorders resulting from aberrant local translation. Here we find that CNOT7, the major deadenylase in eukaryotic cells, takes on the distinct role of regulating local translation in the hippocampus. Depletion of CNOT7 from cultured neurons affects the poly(A) state, localization, and translation of dendritic mRNAs while having little effect on the global neuronal mRNA population. Following synaptic activity, CNOT7 is rapidly degraded resulting in polyadenylation and a change in the localization of its target ...


Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin 2017 University of Missouri - St. Louis

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence ...


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