Diseases Commons^™

Strategies For Enriching Variant Coverage In Candidate Disease Loci On A Multiethnic Genotyping Array, Stephanie Bien, Genevieve L. Wojcik, Niha Zubair, Christopher Gignoux, Alicia R. Martin, Lisa W. Martin, Page Study Investigators

Medicine Faculty Publications

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA) …

Epidemiology Of White Spot Syndrome Virus In The Daggerblade Grass Shrimp (Palaemonetes Pugio) And The Gulf Sand Fiddler Crab (Uca Panacea), Muhammad

Dissertations

Ever since the first outbreaks of White spot syndrome virus (WSSV), which causes White Spot Disease (WSD), in Asia in the early 1990s, the pathogen has been a major constraint to the profitability of the shrimp aquaculture industry across the globe. WSSV has a broad host range and is routinely detected in wild decapod crustaceans. In the present study, two common species in the tidal salt marsh along the northern coast of the Gulf of Mexico, the daggerblade grass shrimp (Palaemonetes pugio) and the Gulf sand fiddler crab (Uca panacea), were investigated for their role as …

Evolving Healthy Populations, Nina H. Fefferman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Influence Of Preventive Measures To Eradicate The Spread Of The Zika Arbovirus, Pradyuta Padmanabhan, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Impact Of Devil Facial Tumor Disease On The Tasmanian Devil Age Structure, Christopher Bruno, Vashni Vasquez

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Kinetics Of Type 1 Interferons During Influenza Virus Infection, Margaret A. Myers

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Optimal Control Of Vaccination Rate In An Epidemiological Model Of Clostridium Difficile Transmission, Brittany Stephenson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Investigating Stromal Contributions To The Regulation Of Cancer Progression, Krista M. Vincent

Electronic Thesis and Dissertation Repository

Tumours are not insular masses of proliferating cells, rather tumour cells evolve within a complex local environment complete with matrix, stromal, and immune components. Therefore, successful tumour growth and eventual metastasis is not determined solely by tumour cells themselves, but also by the fitness advantage or disadvantage conferred by their local environment. However, many of our current cancer models are composed solely of tumour cell isolates. As tumour fitness is dependent on the entire local cellular context, we were interested in characterizing the accuracy of cell lines as models of the tumour microenvironment, with a focus on the secreted Frizzled-related …

The Development Of Novel Imaging Modalities & High-Throughput Drug Screening Platforms In The Drosophila Melanogaster Model Of Human Calcium Oxalate Nephrolithiasis, Sohrab Naushad Ali

Electronic Thesis and Dissertation Repository

Nephrolithiasis is a common urological disorder. Despite advances in the surgical treatment of kidney stone disease, research into its prevention and medical management remain stagnant. This is due to lack of viable pre-clinical models to study the disorder. In this project, we develop and characterize a robust Drosophila melanogaster model for human calcium oxalate nephrolithiasis. Using this model, we have developed intravital imaging techniques to study stone formation and novel high-throughput drug screening platforms. We successfully demonstrate calcium oxalate stone formation by sodium oxalate and ethylene glycol supplementation, with subsequent intravital imaging using bisphosphonate based fluorescent probes. Screening of 360 …

A Generalized-Growth Model To Characterize The Early Ascending Phase Of Infectious Disease Outbreaks, Cecile Viboud, Lone Simonsen, Gerardo Chowell

Global Health Faculty Publications

Background

A better characterization of the early growth dynamics of an epidemic is needed to dissect the important drivers of disease transmission, refine existing transmission models, and improve disease forecasts.

Materials and methods

We introduce a 2-parameter generalized-growth model to characterize the ascending phase of an outbreak and capture epidemic profiles ranging from sub-exponential to exponential growth. We test the model against empirical outbreak data representing a variety of viral pathogens in historic and contemporary populations, and provide simulations highlighting the importance of sub-exponential growth for forecasting purposes.

Results

We applied the generalized-growth model to 20 infectious disease outbreaks representing …

Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, Katherine P. Mueller

Lawrence University Honors Projects

DAF-19, the only RFX transcription factor found in C. elegans, is required for the formation of neuronal sensory cilia. Four isoforms of the DAF-19 protein have been reported, and the m86 nonsense (null) mutation affecting all four isoforms has been shown to prevent cilia formation. Transcriptome analyses employing microarrays of L1 and adult stage worms were completed using RNA from daf-19(m86) worms and an isogenic wild type strain to identify additional putative DAF-19 target genes. Using transcriptional fusions with GFP, we compared the expression patterns of several potential gene targets using fluorescence confocal microscopy. Expression patterns were characterized in …

A Bi-Stable Switch In Virus Dynamics Can Explain The Differences In Disease Outcome Following Siv Infections In Rhesus Macaques, Stanca Ciupe, Christopher Miller, Jonathan Forde

Biology and Medicine Through Mathematics Conference

No abstract provided.

Determinants Of The Efficacy Of Hiv Latency Reversing Agents And Implications For Drug And Treatment Design, Ruian Ke

Biology and Medicine Through Mathematics Conference

No abstract provided.

Using Mathematical Modeling To Unmask The Concealed Nature Of Long Qt-3 Syndrome, Steven Poelzing, Amara Greer-Short, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Influence Of Temperature Variation On Dengue Fever: A Model-Based Investigation, Michael A. Robert, Paula D. Weber, Rebecca C. Christofferson, Christopher N. Mores, Helen J. Wearing

Biology and Medicine Through Mathematics Conference

No abstract provided.

Optimal Insecticide-Treated Bed-Net Coverage And Malaria Treatment In A Malaria-Hiv Co-Infection Model, Eric Numfor

Biology and Medicine Through Mathematics Conference

No abstract provided.

A Mathematical Model Of The Spread Of Dengue Fever Incorporating Mobility, Kelly A. Reagan

Biology and Medicine Through Mathematics Conference

No abstract provided.

Global Dynamics Of A Model Of Joint Hormone Treatment With Dendritic Cell Vaccine For Prostate Cancer, Erica M. Rutter, Yang Kuang

Biology and Medicine Through Mathematics Conference

No abstract provided.

Can Including Time Delay In Epidemic Models Significantly Improve Predictions Concerning Intervention Strategies?, Adrienna N. Bingham, Leah Shaw

Biology and Medicine Through Mathematics Conference

No abstract provided.

Low Energy Defibrillation By Synchronization; 90 % Less Energy Compared To One Shock., Flavio H. Fenton, Yanyan Ji, Ilija Uzelac, Niels Otani, Elizabeth M. Cherry

Biology and Medicine Through Mathematics Conference

No abstract provided.

An Initial Analysis Of A Long-Term Ketogenic Diet’S Impact On Motor Behavior, Brain Purine Systems, And Nigral Dopamine Neurons In A New Genetic Rodent Model Of Parkinson’S Disease, Jacob Rubin, William H. Church

Senior Theses and Projects

A growing body of research suggests that dopaminergic cell death seen in Parkinson’s disease is caused by mitochondrial dysfunction. Oxidative stress, with subsequent generation of reactive oxygen species, is the hallmark biochemical product of mitochondrial dysfunction. The ketogenic diet has been found to enhance mitochondrial energy production, protect against reactive oxygen species-generated cell death, and increase adenosine, a purine that modulates dopamine activity. The current study evaluates the effects of a long-term (5-month) ketogenic diet on behavioral, neurochemical, and neuroanatomical measures in PINK1-KO rats, a new animal model of Parkinson’s disease. Both wild-type and PINK1-KO animals fed a ketogenic diet …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

An Initial Analysis Of A Long-Term Ketogenic Diet’S Impact On Motor Behavior, Brain Purine Systems, And Nigral Dopamine Neurons In A New Genetic Rodent Model Of Parkinson’S Disease, Jacob Rubin, William H. Church

Masters Theses

A growing body of research suggests that dopaminergic cell death seen in Parkinson’s disease is caused by mitochondrial dysfunction. Oxidative stress, with subsequent generation of reactive oxygen species, is the hallmark biochemical product of mitochondrial dysfunction. The ketogenic diet has been found to enhance mitochondrial energy production, protect against reactive oxygen species-generated cell death, and increase adenosine, a purine that modulates dopamine activity. The current study evaluates the effects of a long-term (5-month) ketogenic diet on behavioral, neurochemical, and neuroanatomical measures in PINK1-KO rats, a new animal model of Parkinson’s disease. Both wild-type and PINK1-KO animals fed a ketogenic diet …

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Identification Of Genetic Variation And Haplotype Structure Of The Canine Abca4 Gene For Retinal Disease Association Studies, Barbara Zangerl, Sarah J. Lindauer, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Over 200 mutations in the retina specific member of the ATP-binding cassette transporter superfamily (ABCA4) have been associated with a diverse group of human retinal diseases. The disease mechanisms, and genotype–phenotype associations, nonetheless, remain elusive in many cases. As orthologous genes are commonly mutated in canine models of human blinding disorders, canine ABCA4 appears to be an ideal candidate gene to identify and study sequence changes in dogs affected by various forms of inherited retinal degeneration. However, the size of the gene and lack of haplotype assignment significantly limit targeted association and/or linkage approaches. This study assessed the naturally observed …

Modeling The Structural Consequences Of Best1 Missense Mutations, Karina E. Guziewicz, Gustavo D. Aguirre, Barbara Zangerl

Gustavo D. Aguirre, VMD, PhD

Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied …

Bone Marrow Transplantation For Feline Mucopolysaccharidosis I, Norman Matthew Ellinwood, Marie-Anne Colle, Margaret A. Weil, Margret L. Casal, Charles H. Vite, Staci Wiemelt, Christopher W. Hasson, Thomas M. O'Malley, Xingxuan He, Ulana Prociuk, Lucie Verot, John R. Melniczek, Anne Lannon, Gustavo D. Aguirre, Van W. Knox, Sydney M. Evans, Marie T. Vanier, Edward H. Schuchman, Steven U. Walkley, Mark E. Haskins

Gustavo D. Aguirre, VMD, PhD

Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107–1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to …

Development And Validation Of A Canine-Specific Profiling Array To Examine Expression Of Pro-Apoptotic And Pro-Survival Genes In Retinal Degenerative Diseases, Sem Genini, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

We developed an expression profiling array to examine pro-apoptotic and pro-survival genes in dog retinal degeneration models. Gene-specific canine TaqMan assays were developed and included in a custom real-time quantitative reverse transcription-PCR (qRT-PCR) array. Of the 96 selected genes, 93 belonged to known relevant pro-apoptotic and pro-survival pathways, and/or were positive controls expressed in retina, while three were housekeeping genes. Ingenuity Pathway Analysis (IPA) showed that the selected genes belonged to expected biological functions (cell death, cell-mediated immune response, cellular development, function, and maintenance) and pathways (death receptor signaling, apoptosis, TNFR1 signaling, and induction of apoptosis by HIV1). Validation of …

Linkage Disequilibrium Mapping In Domestic Dog Breeds Narrows The Progressive Rod-Cone Degeneration Interval And Identifies Ancestral Disease-Transmitting Chromosome, Orly Goldstein, Barbara Zangerl, Sue Pearce-Kelling, Duska J. Sidjanin, James W. Kijas, Jeanette Felix, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Canine progressive rod–cone degeneration (prcd) is a retinal disease previously mapped to a broad, gene-rich centromeric region of canine chromosome 9. As allelic disorders are present in multiple breeds, we used linkage disequilibrium (LD) to narrow the ∼6.4-Mb interval candidate region. Multiple dog breeds, each representing genetically isolated populations, were typed for SNPs and other polymorphisms identified from BACs. The candidate region was initially localized to a 1.5-Mb zero recombination interval between growth factor receptor-bound protein 2 (GRB2) and SEC14-like 1 (SEC14L). A fine-scale haplotype of the region was developed, which reduced the LD interval to 106 kb and identified …