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Full-Text Articles in Diseases

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan Feb 2019

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that EGCG prevents …


Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval Feb 2019

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT4R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT4R expression …


An In Vitro And In Vivo Evaluation Of The Anticancer Potential Of Resveratrol And Pterostilbene Against Hpv-E6 Positive Cancers, Kaushiki Chatterjee Feb 2019

An In Vitro And In Vivo Evaluation Of The Anticancer Potential Of Resveratrol And Pterostilbene Against Hpv-E6 Positive Cancers, Kaushiki Chatterjee

Dissertations, Theses, and Capstone Projects

Cervical cancer remains as one of the most prevalent cancers effecting women globally. Lack of awareness and affordable prophylactic and therapeutic options in developing countries drive the need for alternative low-cost approaches. Dietary polyphenols have gained increased attention as possible anti-cancer agents. Our study aims to investigate whether two natural structural analogs, resveratrol and pterostilbene, exhibit anti-HPV (Human papillomavirus) activity in cervical cancer. To determine the efficacy of these polyphenols, extensive in vitro and in vivo analyses were carried out. For the in vitro studies we utilized human HeLa cells (HPV18 positive) and murine TC1 cells (HPV 16 oncogene positive). …


Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner Jan 2019

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …


Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang Jan 2019

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …


Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan Jan 2019

Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan

Yale Day of Data

Whole transcriptome wide gene expression profiles in the sputum and circulation from 100 asthma patients were measured using the Affymetrix HuGene 1.0ST arrays. Unsupervised clustering analysis based on pathways from KEGG were used to identify TEA clusters of patients from the sputum gene expression profiles. The identified TEA clusters have significantly different pre-bronchodilator FEV1, bronchodilator responsiveness, exhaled nitric oxide levels, history of hospitalization for asthma and history of intubation. Evaluation of TEA clusters in children from Asthma BRIDGE cohort confirmed the identified differences in intubation and hospitalization. Furthermore, evaluation of the TH2 gene signatures suggested a much lower prevalence of …


Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp Jan 2019

Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp

Yale Day of Data

This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.


The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria Jan 2019

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …


Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks Jan 2019

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …


A Bird's-Eye View Of The Multiple Biochemical Mechanisms That Propel Pathology Of Alzheimer's Disease: Recent Advances And Mechanistic Perspectives On How To Halt The Disease Progression Targeting Multiple Pathways., Caleb Vegh, Kyle Stokes, Dennis Ma, Darcy Wear, Jerome Cohen, Sidhartha D. Ray, Siyaram Pandey Jan 2019

A Bird's-Eye View Of The Multiple Biochemical Mechanisms That Propel Pathology Of Alzheimer's Disease: Recent Advances And Mechanistic Perspectives On How To Halt The Disease Progression Targeting Multiple Pathways., Caleb Vegh, Kyle Stokes, Dennis Ma, Darcy Wear, Jerome Cohen, Sidhartha D. Ray, Siyaram Pandey

Touro College of Pharmacy (New York) Publications and Research

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including …


Effect Of Propionic Acid-Derivative Ibuprofen On Neural Stem Call Differentiation; A Potential Link To Autism Spectrum Disorder, Aseelia Samsam Jan 2019

Effect Of Propionic Acid-Derivative Ibuprofen On Neural Stem Call Differentiation; A Potential Link To Autism Spectrum Disorder, Aseelia Samsam

Honors Undergraduate Theses

Propionic acid (PPA) is a short chain fatty acid that is produced by the human gut microbiome. Propionate, butyrate and acetates are the end products of the fermentation of the complex carbohydrates by human gut friendly microbiome and are being used as sources of energy in our body. PPA is used as a food preservative against molds in various daily products and has been implicated in the pathogenesis of autism. In a recent study we showed that PPA in human neuronal stem cell (NSC) culture increases the astrocyte population and decreases the neuronal number and increases the inflammatory cytokines. In …


White Matter Hyperintensities In Vascular Contributions To Cognitive Impairment And Dementia (Vcid): Knowledge Gaps And Opportunities, Jessica Alber, Suvarna Alladi, Hee-Joon Bae, David A. Barton, Laurel A. Beckett, Joanne M. Bell, Sara E. Berman, Geert Jan Biessels, Sandra E. Black, Isabelle Bos, Gene L. Bowman, Emanuele Brai, Adam M. Brickman, Brandy L. Callahan, Roderick A. Corriveau, Silvia Fossati, Rebecca F. Gottesman, Deborah R. Gustafson, Vladimir Hachinski, Kathleen M. Hayden, Alex M. Helman, Timothy M. Hughes, Jeremy D. Isaacs, Angela L. Jefferson, Sterling C. Johnson, Alifiya Kapasi, Silke Kern, Jay C. Kwon, Juraj Kukolja, Athene Lee, Brittani R. Price, Donna M. Wilcock Jan 2019

White Matter Hyperintensities In Vascular Contributions To Cognitive Impairment And Dementia (Vcid): Knowledge Gaps And Opportunities, Jessica Alber, Suvarna Alladi, Hee-Joon Bae, David A. Barton, Laurel A. Beckett, Joanne M. Bell, Sara E. Berman, Geert Jan Biessels, Sandra E. Black, Isabelle Bos, Gene L. Bowman, Emanuele Brai, Adam M. Brickman, Brandy L. Callahan, Roderick A. Corriveau, Silvia Fossati, Rebecca F. Gottesman, Deborah R. Gustafson, Vladimir Hachinski, Kathleen M. Hayden, Alex M. Helman, Timothy M. Hughes, Jeremy D. Isaacs, Angela L. Jefferson, Sterling C. Johnson, Alifiya Kapasi, Silke Kern, Jay C. Kwon, Juraj Kukolja, Athene Lee, Brittani R. Price, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to …


Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal Jan 2019

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …


Waist Circumference And The Relation To Aerobic Exercise And Perception Of Illness In Adults With Type 2 Diabetes Mellitus, Bailey J. Huebner Jan 2019

Waist Circumference And The Relation To Aerobic Exercise And Perception Of Illness In Adults With Type 2 Diabetes Mellitus, Bailey J. Huebner

Masters Theses

The purpose of this study was to observe the relationship between waist circumference (WC), amount of aerobic exercise performed weekly and overall Health Belief Model (HBM) score in adults with diagnosed type 2 diabetes mellitus (T2DM). Members from a local Midwest adult fitness program (n = 5) who had been diagnosed T2DM participated in this study. Participants ranged in age from 70 to 80 years with an average age of 74 years. Four of the participants were female and one participant was male. The questions included in this study were 1 .) in those with diagnosed T2DM, was a low …


A 3d Bioprinter Platform For Mechanistic Analysis Of Tumoroids And Chimeric Mammary Organoids, John A. Reid, Xavier-Lewis Palmer, Peter A. Mollica, Nicole Northam, Patrick C. Sachs, Robert D. Bruno Jan 2019

A 3d Bioprinter Platform For Mechanistic Analysis Of Tumoroids And Chimeric Mammary Organoids, John A. Reid, Xavier-Lewis Palmer, Peter A. Mollica, Nicole Northam, Patrick C. Sachs, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise …


Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan Jan 2019

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …


How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond Jan 2019

How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond

World of Viruses

Equitable learning opportunities are critical to the goals of science education. However, major curriculum standards are vague on how to achieve equity goals, and educators must often develop their own resources and strategies to achieve equity goals. This study examines how educators used a comic book series designed to interest youth in virology as a way to make science more broadly appealing to their diverse students. We begin with the notion of Pedagogical Design Capacity, which describes a dynamic relationship between teachers and their tools and the ability for teachers to perceive and leverage affordances of artifacts as tools in …


Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak Jan 2019

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …


Elucidating The Role Of Oxygen And Biotype In The Environmental Persistence Of Vibrio Cholerae, Amy M. Freiberg Jan 2019

Elucidating The Role Of Oxygen And Biotype In The Environmental Persistence Of Vibrio Cholerae, Amy M. Freiberg

Honors Undergraduate Theses

Vibrio cholerae is a natural inhabitant of aquatic environments and serves as the etiological agent for the severe diarrheal disease, cholera. Cholera epidemics follow a regular seasonal pattern, which account for tens to hundreds of thousands of deaths in a given year. V. choleraenaturally persist between epidemics through entry into a dormant state known as viable but nonculturable (VBNC). Research has shown that V. choleraein this VBNC state experience drastic morphological and metabolic changes, which serve as survival mechanisms until environmental conditions become suitable again. The natural marine ecosystem that V. cholerae inhabitis comprised of a complex …


Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford Jan 2019

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …


Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian Jan 2019

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …


Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria Jan 2019

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …


Multistate Survey Of American Dog Ticks (Dermacentor Variabilis) For Rickettsia Species, Joy A. Hecht, Michelle E.J. Allerdice, Elizabeth A. Dykstra, Laura Mastel, Rebecca J. Eisen, Tammi L. Johnson, Holly D. Gaff, Andrea S. Varela-Stokes, Jerome Goddard, Benedict B. Pagac, Christopher D. Paddock, Sandor E. Karpathy Jan 2019

Multistate Survey Of American Dog Ticks (Dermacentor Variabilis) For Rickettsia Species, Joy A. Hecht, Michelle E.J. Allerdice, Elizabeth A. Dykstra, Laura Mastel, Rebecca J. Eisen, Tammi L. Johnson, Holly D. Gaff, Andrea S. Varela-Stokes, Jerome Goddard, Benedict B. Pagac, Christopher D. Paddock, Sandor E. Karpathy

Biological Sciences Faculty Publications

Dermacentor variabilis, a common human-biting tick found throughout the eastern half and along the west coast of the United States, is a vector of multiple bacterial pathogens. Historically, D. variabilis has been considered a primary vector of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. A total of 883 adult D. variabilis, collected between 2012 and 2017 from various locations in 12 states across the United States, were screened for rickettsial DNA. Tick extracts were evaluated using three real-time PCR assays; an R. rickettsii-specific assay, a Rickettsia bellii-specific assay, and a Rickettsia genus-specific …


Host Factors Against Plant Viruses, Hernan García-Ruiz Jan 2019

Host Factors Against Plant Viruses, Hernan García-Ruiz

Department of Plant Pathology: Faculty Publications

Plant virus genome replication and movement is dependent on host resources and factors. However, plants respond to virus infection through several mechanisms, such as autophagy, ubiquitination, mRNA decay and gene silencing, that target viral components. Viral factors work in synchrony with pro-viral host factors during the infection cycle and are targeted by antiviral responses. Accordingly, establishment of virus infection is genetically determined by the availability of the pro-viral factors necessary for genome replication and movement, and by the balance between plant defence and viral suppression of defence responses. Sequential requirement of pro-viral factors and the antagonistic activity of antiviral factors …


Effects Of The Dual Orexin Receptor Antagonist Dora-22 On Sleep In 5xfad Mice, Marilyn J. Duncan, Hannah Farlow, Chairtra Tirumalaraju, Do-Hyun Yun, Chanung Wang, James A. Howard, Madison N. Sanden, Bruce F. O'Hara, Kristen J. Mcquerry, Adam D. Bachstetter Jan 2019

Effects Of The Dual Orexin Receptor Antagonist Dora-22 On Sleep In 5xfad Mice, Marilyn J. Duncan, Hannah Farlow, Chairtra Tirumalaraju, Do-Hyun Yun, Chanung Wang, James A. Howard, Madison N. Sanden, Bruce F. O'Hara, Kristen J. Mcquerry, Adam D. Bachstetter

Neuroscience Faculty Publications

Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD.

Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Aβ plaques, Aβ levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively.

Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Aβ levels, …


Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn Jan 2019

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …


Anti-C1q Autoantibodies Are Frequently Detected In Patients With Systemic Sclerosis Associated With Pulmonary Fibrosis, C. Liaskos, S. Rentouli, T. Simopoulou, A. Gkoutzourelas, G. L. Norman, A. Brotis, I. Alexiou, C. Katsiari, D. P. Bogdanos, L. I. Sakkas Jan 2019

Anti-C1q Autoantibodies Are Frequently Detected In Patients With Systemic Sclerosis Associated With Pulmonary Fibrosis, C. Liaskos, S. Rentouli, T. Simopoulou, A. Gkoutzourelas, G. L. Norman, A. Brotis, I. Alexiou, C. Katsiari, D. P. Bogdanos, L. I. Sakkas

Biological Sciences Faculty Publications

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE) but their presence in other rheumatic diseases has not been adequately investigated.

OBJECTIVE: We aim to assessanti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc).

METHODS: One hundred twenty four patients with SSc (106 females; median age 59.4 years, range 25-81.4; 75(60.5%) with limited cutaneous SSc[lcSSc], and 49(39.5%) with diffuse cutaneous SSc[dcSSc]), were studied. Twenty-five patients with Sjögren's syndrome (SjS), 29 with rheumatoid arthritis (RA), and 38 patients with systemic lupus erythematosus (SLE) and 53 healthy controls (NC) were also included. ELISAs with high and low salt …


Field Testing Integrated Interventions For Schistosomiasis Elimination In The People's Republic Of China: Outcomes Of A Multifactorial Cluster-Randomized Controlled Trial, Gail M. Williams, Yue-Sheng Li, Darren J. Gray, Zheng-Yuan Zhao, Donald A. Harn, Lisa M. Shollenberger, Sheng-Ming Li, Xinglin Yu, Zeng Feng, Jia-Gang Guo, Jie Zhou, Yu-Lan Dong, Yuan Li, Biao Guo, Patrick Driguez, Marina Harvie, Hong You, Allen G. Ross, Donald P. Mcmanus Jan 2019

Field Testing Integrated Interventions For Schistosomiasis Elimination In The People's Republic Of China: Outcomes Of A Multifactorial Cluster-Randomized Controlled Trial, Gail M. Williams, Yue-Sheng Li, Darren J. Gray, Zheng-Yuan Zhao, Donald A. Harn, Lisa M. Shollenberger, Sheng-Ming Li, Xinglin Yu, Zeng Feng, Jia-Gang Guo, Jie Zhou, Yu-Lan Dong, Yuan Li, Biao Guo, Patrick Driguez, Marina Harvie, Hong You, Allen G. Ross, Donald P. Mcmanus

Biological Sciences Faculty Publications

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicum infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the S. japonicum, lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) …


A Review Of Rat Lungworm Infection And Recent Data On Its Definitive Hosts In Hawaii, Chris N. Niebuhr, Susan I. Jarvi, Shane R. Siers Jan 2019

A Review Of Rat Lungworm Infection And Recent Data On Its Definitive Hosts In Hawaii, Chris N. Niebuhr, Susan I. Jarvi, Shane R. Siers

Human–Wildlife Interactions

Rat lungworm (Angiostrongylus cantonensis) is a zoonotic nematode that causes rat lungworm disease (angiostrongyliasis), a potentially debilitating form of meningitis, in humans worldwide. The definitive hosts for rat lungworm are primarily members of the genus Rattus, with gastropods as intermediate hosts. This parasite has emerged as an important public health concern in the United States, especially in Hawaii, where the number of human cases has increased in the last decade. Here we discuss the current knowledge of the rat lungworm, including information on the life cycle and host species, as well as updates on known infection levels. Three …


Investigating Iron Metabolism In Subarachnoid Hemorrhage Patients, Alexander A. Maynard, Gardenia Pacheco Jan 2019

Investigating Iron Metabolism In Subarachnoid Hemorrhage Patients, Alexander A. Maynard, Gardenia Pacheco

Williams Honors College, Honors Research Projects

Subarachnoid hemorrhage (SAH) is a stroke characterized by bleeding into the subarachnoid space of the brain, typically resulting in high mortality rate.8 Delayed cerebral ischemia (DCI), characterized by vasospasms induced arterial constriction, occurs in roughly one third of the surviving patients.20 The development of DCI and neurodegeneration could be linked to metabolic pathology that occurs after SAH, specifically iron induced changes in redox status. The oxidized environment induced by iron has the potential to functionally affect the ferroxidase ceruloplasmin (Cp), which is linked to neurodegeneration.15 Global LC-MS based metabolomics data revealed alterations in metabolism in the CSF …