Disease Modeling Commons^™

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.

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

Dissertations and 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 …

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 …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

Editorial: Biology Of Cognitive Aging: Model Systems, Technologies, And Beyond, Shin Murakami

Faculty Publications & Research of the TUC College of Osteopathic Medicine

The author provides an introduction to a research issue of Frontiers in Genetics on models and techniques related to age-related memory impairment.

Selective Mutation Accumulation: A Computational Model Of The Paternal Age Effect, Eoin C. Whelan, Alexander C. Nwala, Christopher Osgood, Stephan Olariu

Biological Sciences Faculty Publications

Motivation: As the mean age of parenthood grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father, but have a deleterious effect in offspring. In this paper we present a computational technique to model the SSC niche in order to examine the phenomenon and draw conclusions across different genes and disorders.

Results: We used a Markov chain to model the probabilities of …

Assessing The Expression Of Astrocytic Markers In Retinal Ganglion Cell Projection Of Lcr/Hcr Rats, Isabella K. Bartholomew, Samuel Crish, James Holda, Jordan Renna, Gina Wilson

Williams Honors College, Honors Research Projects

Metabolic Syndrome is a human condition that presents with various metabolic issues such as abnormal distribution of body fat, high blood pressure, and a prothrombotic state, among other problems (Alberti,et al, 2005). This syndrome is a risk factor for visual disorders, such as glaucoma, and is often associated with increased levels of neuroinflammation. Currently, the animal model used to replicate this syndrome is The Low Capacity Runner and High Capacity Runner Rat Model. These rats have been bred based on their running capacities for 30+ generations to have drastic metabolic differences. We assessed key areas of the retinal ganglion cell …

Modulation Of Body Weight By Intestinal Flora In Orphan Nuclear Receptor Shp-/- Mice, Ryan Mifflin

Williams Honors College, Honors Research Projects

The whole-body deletion of small heterodimer partner (SHP) in mice is associated with protection from diet-induced obesity and hepatic steatosis upon feeding of a western diet. This protection was reported to be mediated through decreases in hepatic gene expression for lipogenesis, as well as increases in gene expression for fatty acid oxidation. SHP has been known to regulate the expression of the CYP7A1 gene, encoding the rate-limiting enzyme for bile acid synthesis, thereby altering the bile acid pool. The effects of this altered bile acid profile on the gut microbiome are unknown, as some bacteria in the gut are responsible …

“The Most Poisonous Of All Diseases Of Mind Or Body”: Colorphobia And The Politics Of Reform, April J. Gemeinhardt

Graduate Student Theses, Dissertations, & Professional Papers

Focusing on the mid-1830s through 1865, this thesis explores colorphobia—the irrational fear and hatred of black people otherwise known as racial prejudice—as a reform tactic adopted by abolitionists. It argues that colorphobia played a pivotal role in the radical abolitionist reform agenda for promoting anti-slavery, immediate emancipation, equal rights, and black advancement. By framing racial prejudice as a disease, abolitionists believed connotations, stigmas, and fears of illness would elicit more attention to the rapidly increasing racial prejudice in the free North and persuade prejudiced white Americans into changing their ways. Abolitionists used parallels to cholera, choleraphobia (fear of cholera), and …

Space-Time Modelling Of Emerging Infectious Diseases: Assessing Leptospirosis Risk In Sri Lanka, Cameron C F Plouffe

Theses and Dissertations (Comprehensive)

In this research, models were developed to analyze leptospirosis incidence in Sri Lanka and its relation to rainfall. Before any leptospirosis risk models were developed, rainfall data were evaluated from an agro-ecological monitoring network for producing maps of total monthly rainfall in Sri Lanka. Four spatial interpolation techniques were compared: inverse distance weighting, thin-plate splines, ordinary kriging, and Bayesian kriging. Error metrics were used to validate interpolations against independent data. Satellite data were used to assess the spatial pattern of rainfall. Results indicated that Bayesian kriging and splines performed best in low and high rainfall, respectively. Rainfall maps generated from …

Effect Of Genetic Background On The Dystrophic Phenotype In Mdx Mice., William D Coley, Laurent Bogdanik, Maria Candida Vila, Qing Yu, Terence A Partridge, Kanneboyina Nagaraju, +12 Additional Authors

Genomics and Precision Medicine Faculty Publications

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them to the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared to their respective …

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations and Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

Age-Dependent Breakdown Of The Blood Brain Barrier And Associated Changes In S100b Ko Mice, Eric V. Brown

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies play an important role in many autoimmune diseases. Recent research has shown that breakdown of the blood brain barrier (BBB) occurs concomitant to generation of brain reactive autoantibodies in many neurodegenerative diseases, which serve as biomarkers and drivers of pathology. SI00B, a calcium binding protein found most highly expressed in astrocytes which ensheathe the BBB, has many functions in neural development and signaling. Currently literature indicates that S100B KO mice develop normally, with no phenotypic abnormalities. Here, it is demonstrated that S100B KO mice seem to develop a chronic BBB breakdown similar to that seen in human neurodegenerative diseases. …

Human Animal Chimeras For Therapeutic Protocols, Bracha Sklar

The Science Journal of the Lander College of Arts and Sciences

Research on humans is limited, therefore human animal chimeras have been used to study human systems. A Human animal chimera is an animal containing animal and human cell lines. The primary goal of human animal chimera research is to establish an animal with human cellular characters, which can and should more realistically be able to imitate as closely as possible the in vivo situations in humans. This research is very important, because it allows scientists to study human systems in vivo using a humanized animal model. However ethical issues arise when experimenting with humans and animals being mixed together. Using …

Information Maximizing Component Analysis Of Left Ventricular Remodeling Due To Myocardial Infarction, Xingyu Zhang, Bharath Ambale-Venkatesh, David A. Bluemke, Brett R. Cowan, J. Paul Finn, Alan H. Kadish, Pau Medrano-Gracia

Office of the President Publications and Research

Background: Although adverse left ventricular shape changes (remodeling) after myocardial infarction (MI) are predictive of morbidity and mortality, current clinical assessment is limited to simple mass and volume measures, or dimension ratios such as length to width ratio. We hypothesized that information maximizing component analysis (IMCA), a supervised feature extraction method, can provide more efficient and sensitive indices of overall remodeling.

Methods: IMCA was compared to linear discriminant analysis (LDA), both supervised methods, to extract the most discriminatory global shape changes associated with remodeling after MI. Finite element shape models from 300 patients with myocardial infarction from the …

Functional Characterization Of Rai1 In Zebrafish, Joshua S. Beach

Theses and Dissertations

Smith-Magenis Syndrome (SMS; OMIM #182290) is a multiple congenital abnormality and intellectual disability (ID) disorder caused by either an interstitial deletion of the 17p11.2 region containing the retinoic acid induced-1 (RAI1) gene or a mutation of the RAI1 gene. Individuals diagnosed with SMS typically present characteristics such as ID, self-injurious behavior, sleep disturbance, ocular and otolaryngological abnormalities, craniofacial and skeletal abnormalities, neurological and behavioral abnormalities, as well as other systemic defects and manifestations. Previous work by Vyas in 2009 showed temporal expression of rai1 in zebrafish embryos as early as 9 hpf. We hypothesize that there is maternal …

Development Of In Vitro Denture Biofilm Models For Halitosis Related Bacteria And Their Application In Testing The Efficacy Of Antimicrobial Agents, Tingxi Wu, Xuesong He, David J. Bradshaw, Alyson Axe, Zvi G. Loewy, Honghu Liu, Renate Lux

Touro College of Pharmacy (New York) Publications and Research

Objective: Since dentures can serve as a reservoir for halitosis-causing oral bacteria, halitosis development is a concern for denture wearers. In this study, we surveyed the prevalence of four selected halitosis-related species (Fusobacterium nucleatum, Tannerella forsythia, Veillonella atypica and Klebsiella pneumoniae) in clinical denture plaque samples, and developed denture biofilm models for these species in vitro to facilitate assessment of antimicrobial treatment efficacy. Design: Denture plaque from ten healthy and ten denture stomatitis patients was screened for the presence of aforementioned four species by PCR. Biofilm formation by these halitosis-associated species on the surfaces of denture …

Neural Stem Cells As A Model To Study Huntington’S Disease, Rawan Bakhsh

Dissertations, Masters Theses, Capstones, and Culminating Projects

Huntington’s disease (HD) is a heritable neurodegenerative disorder that affects muscle coordination and diminishes cognitive abilities, by affecting the medium spiny neurons in the brain. In HD patients, neurons are damaged and destroyed because of the toxicity of the mutant Huntington protein (mHtt). The mechanism of how mHtt protein affects the neurons is unknown. In this study we explored the effects of mHtt expression by looking at changes in huntingtin localization, changes in the expression and co-localization of related proteins and differences in cell morphology. We examine how this expression affects the cytoskeletal structures using neural stem cells Q7 (wild …

Nack Is An Integral Component Of The Notch Transcriptional Activation Complex And Is Critical For Development And Tumorigenesis, Kelly L Weaver, Marie-Clotilde Alves-Guerra, Ke Jin, Zhiqiang Wang, Xiaoqing Han, Prathibha Ranganathan, Xiaoxia Zhu, Thiago Dasilva, Wei Liu, Francesca Ratti, Renee M Demarest, Cristos Tzimas, Meghan Rice, Rodrigo Vasquez-Del Carpio, Nadia Dahmane, David J Robbins, Anthony J Capobianco

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are …