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Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu May 2016

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …


Improving Access To Care For Arkansas Youth Athletes With Sport-Related Concussion: Establishing “Teleconcussion” In Arkansas, Kristin Maxey May 2016

Improving Access To Care For Arkansas Youth Athletes With Sport-Related Concussion: Establishing “Teleconcussion” In Arkansas, Kristin Maxey

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Proper management of sport-related concussion (SRC) is critical for improved recovery outcomes in youth athletes. Several barriers exist to improving the standard of care for youth athletes with SRC. Many rural areas lack medical professionals with specialized training in SRC. Innovative methods for providing specialized healthcare to youth athletes with SRC are needed. Telehealth may be an effective means of providing specialized care for youth athletes with SRC located in underserved areas that have a shortage of healthcare providers specializing in SRC.

Purpose: The purpose of this study was to compare patient, caregiver, and provider ratings of the therapeutic …


Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun May 2016

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …


Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian May 2016

Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian

Electronic Theses and Dissertations

SA-4-1BBL is a recombinant costimulatory molecule that is active in its soluble form and has pleiotropic effects on the functions of innate, adaptive, and regulatory immune cells. We have previously shown that SA-4-1BBL makes CD4+ T conventional cells (Tconvs) resistant to suppression by CD4+CD25+Foxp3+ T regulatory cells (Tregs). The mechanistic basis of this observation is the subject of this study. We demonstrate that Tconvs, but not Tregs, are the direct targets of SA-4-1BBL-mediated evasion of Treg suppression without contribution from antigen presenting cells (APCs). SA-4-1BBL engagement with its receptor, 4-1BB, on Tconvs resulted in the production of high levels of …


The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan May 2016

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 …


Doulas Could Improve Foreign-Born Women’S Perinatal And Postpartum Satisfaction And Increase Health Providers’ Cultural Competency In A Multicultural Urban Area Of The United States., Crystal Kazik May 2016

Doulas Could Improve Foreign-Born Women’S Perinatal And Postpartum Satisfaction And Increase Health Providers’ Cultural Competency In A Multicultural Urban Area Of The United States., Crystal Kazik

Sustainability and Social Justice

Doulas act as a cultural bridge between clients and providers through the support, advocacy, and education they provide. Unfortunately, migrant women may be at a disadvantage for accessing and benefiting from their services due to a variety of socioeconomic and cultural factors including predisposed ideas of care and structure based on experiences in native countries, language barriers, lower health literacy, and a lack of awareness and understanding from hospital/clinic staff.

A strategic multifaceted approach utilizing doulas, such as Boston Medical Center’s collaborative and culturally competent model, may greatly improve foreign-born women’s experience and satisfaction with healthcare when pregnant and giving …


Diffusion Modeling And Device Development For Peritoneal Membrane Oxygenation, Liana Hatoum May 2016

Diffusion Modeling And Device Development For Peritoneal Membrane Oxygenation, Liana Hatoum

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Acute respiratory distress syndrome (ARDS) is a pulmonary disease that causes hypoxemia and respiratory failure. The mortality rate for ARDS ranges between 27% and 45%. Current treatments including mechanical ventilation and extracorporeal membrane oxygenation (ECMO) are often associated with high risk complications including barotrauma, infection, thrombosis, and hemorrhage. Alternative pulmonary support techniques are needed to improve the survival rate of patients suffering from ARDS. Previous studies introducing pure O2 gas, perfluorocarbons and red blood cells into the intraperitoneal (IP) cavity have reported no effect or only a mild increase in oxygenation. Here we report peritoneal membrane oxygenation (PMO) using …


Induced Stem Cells As A Novel Multiple Sclerosis Therapy., Chong Xie, Yan-Qun Liu, Yang-Tai Guan, Guang-Xian Zhang May 2016

Induced Stem Cells As A Novel Multiple Sclerosis Therapy., Chong Xie, Yan-Qun Liu, Yang-Tai Guan, Guang-Xian Zhang

Department of Neurology Faculty Papers

Stem cell replacement is providing hope for many degenerative diseases that lack effective therapeutic methods including multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Transplantation of neural stem cells or mesenchymal stem cells is a potential therapy for MS thanks to their capacity for cell repopulation as well as for their immunomodulatory and neurotrophic properties. Induced pluripotent stem cell (iPSC), an emerging cell source in regenerative medicine, is also being tested for the treatment of MS. Remarkable improvement in mobility and robust remyelination have been observed after transplantation of iPSC-derived neural cells into demyelinated models. Direct …


Pulmonary Primary Blast Injuries, Moe Uddin Apr 2016

Pulmonary Primary Blast Injuries, Moe Uddin

Honors Scholar Theses

Primary underwater explosions are particularly dangerous because of the water properties relative to air, and the resulting pathologies presents difficulty in determining their etiologies. The whole body is affected by the blast wave and the survivor is considered a trauma patient. The exact mechanism of injury is not well understood. In the literature, there are inconsistencies between the explosive and the resulting outcome of the experimental animals. Primary lung blast injuries is the leading cause of mortality in underwater explosions and this explores the different pathologies, symptoms, and treatments that are currently available.


Circadian Factors Bmal1 And Rorα Control Hif-1Α Transcriptional Activity In Nucleus Pulposus Cells: Implications In Maintenance Of Intervertebral Disc Health., Kaori Suyama, Elizabeth S Silagi, Hyowon Choi, Kou Sakabe, Joji Mochida, Irving M Shapiro, Makarand V Risbud Apr 2016

Circadian Factors Bmal1 And Rorα Control Hif-1Α Transcriptional Activity In Nucleus Pulposus Cells: Implications In Maintenance Of Intervertebral Disc Health., Kaori Suyama, Elizabeth S Silagi, Hyowon Choi, Kou Sakabe, Joji Mochida, Irving M Shapiro, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or …


Aberrant Dna Methylation: Implications In Racial Health Disparity, Xuefeng Wang, Ping Ji, Yuanhao Zhang, Joseph F. Lacomb, Xinyu Tian, Ellen Li, Jennie L. Williams Apr 2016

Aberrant Dna Methylation: Implications In Racial Health Disparity, Xuefeng Wang, Ping Ji, Yuanhao Zhang, Joseph F. Lacomb, Xinyu Tian, Ellen Li, Jennie L. Williams

Department of Biomedical Engineering Faculty Publications

Background Incidence and mortality rates of colorectal carcinoma (CRC) are higher in African Americans (AAs) than in Caucasian Americans (CAs). Deficient micronutrient intake due to dietary restrictions in racial/ethnic populations can alter genetic and molecular profiles leading to dysregulated methylation patterns and the inheritance of somatic to germline mutations. Materials and Methods Total DNA and RNA samples of paired tumor and adjacent normal colon tissues were prepared from AA and CA CRC specimens. Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing were employed to evaluate total genome methylation of 5’-regulatory regions and dysregulation of gene expression, respectively. Robust analysis was …


S100a4 Drives Non-Small Cell Lung Cancer Invasion, Associates With Poor Prognosis, And Is Effectively Targeted By The Fda-Approved Anti-Helminthic Agent Niclosamide, Rachel L. Stewart, Brittany L. Carpenter, Dava S. West, Teresa Knifley, Lili Liu, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, Susanne M. Arnold, Kathleen L. O'Connor, Min Chen Apr 2016

S100a4 Drives Non-Small Cell Lung Cancer Invasion, Associates With Poor Prognosis, And Is Effectively Targeted By The Fda-Approved Anti-Helminthic Agent Niclosamide, Rachel L. Stewart, Brittany L. Carpenter, Dava S. West, Teresa Knifley, Lili Liu, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, Susanne M. Arnold, Kathleen L. O'Connor, Min Chen

Markey Cancer Center Faculty Publications

S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular …


Role Of Dietary Components In Modulating Hypertension, Andrew Feyh, Lucas Bracero, Hari Vishal Lakhani, Prasanna Santhanam, Joseph I. Shapiro Md, Zeid Khitan Md, Komal Sodhi Apr 2016

Role Of Dietary Components In Modulating Hypertension, Andrew Feyh, Lucas Bracero, Hari Vishal Lakhani, Prasanna Santhanam, Joseph I. Shapiro Md, Zeid Khitan Md, Komal Sodhi

Biochemistry and Microbiology

Hypertension is a major health issue, particularly in medically underserved populations that may suffer from poor health literacy, poverty, and limited access to healthcare resources. Management of the disease reduces the risk of adverse outcomes, such as cardiovascular or cerebrovascular events, vision impairment due to retinal damage, and renal failure. In addition to pharmacological therapy, lifestyle modifications such as diet and exercise are effective in managing hypertension. Current diet guidelines include the DASH diet, a low-fat and low-sodium diet that encourages high consumption of fruits and vegetables. While the diet is effective in controlling hypertension, adherence to the diet is …


Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty Apr 2016

Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have …


Geodemographic Features Of Human Blastomycosis In Eastern Wisconsin, Megan E. Huber, Dennis J. Baumgardner, Jessica J. F. Kram, Melissa A. Lemke Apr 2016

Geodemographic Features Of Human Blastomycosis In Eastern Wisconsin, Megan E. Huber, Dennis J. Baumgardner, Jessica J. F. Kram, Melissa A. Lemke

Journal of Patient-Centered Research and Reviews

Purpose

Blastomycosis is an endemic fungal infection. In rural northern Wisconsin, blastomycosis cases are associated with certain environmental features including close proximity to waterways. Other studies have associated blastomycosis with particular soil chemicals. However, blastomycosis also occurs in urban and suburban regions. We explored the geodemographic associations of blastomycosis cases in the more urban/suburban landscape of eastern Wisconsin.

Methods

We conducted a retrospective study of 193 laboratory-identified blastomycosis cases in a single eastern Wisconsin health system, 2007–2015. Controls were 250 randomly selected cases of community-diagnosed pneumonia from a similar time period. Geographic features of home addresses were explored using Google …


Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner Apr 2016

Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

In introducing the infectious disease focus for this edition of the Journal of Patient-Centered Research and Reviews, the author describes the unsolved mysteries surrounding the dimorphic fungus Blastomyces and the related pathogenesis of pulmonary blastomycosis.


Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner Apr 2016

Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

A number of fungal pathogens that may result in a variety of human diseases are found in residential homes and yards. The growth of these microscopic fungi is often favored by particular characteristics of the dwelling and nearby outdoor environment. Evolved virulence factors or increased ability of specific fungi to grow in diverse, and sometimes harsh, microenvironments presented by the domestic environment may promote growth and pathogenesis. Infection may occur by inhalation or direct inoculation and include endemic fungi in addition to opportunistic or emerging species. Systemic or locally aggressive fungal infections are particularly likely and may be life-threatening in …


Nitrilase 1 Modulates Lung Tumor Progression In Vitro And In Vivo., Yong Antican Wang, Yunguang Sun, Justin M Le Blanc, Charalambos C. Solomides, Md, Tingting Zhan, Bo Lu, Md Apr 2016

Nitrilase 1 Modulates Lung Tumor Progression In Vitro And In Vivo., Yong Antican Wang, Yunguang Sun, Justin M Le Blanc, Charalambos C. Solomides, Md, Tingting Zhan, Bo Lu, Md

Department of Radiation Oncology Faculty Papers

Uncovering novel growth modulators for non-small cell lung cancer (NSCLC) may lead to new therapies for these patients. Previous studies suggest Nit1 suppresses chemically induced carcinogenesis of the foregut in a mouse model. In this study we aimed to determine the role of Nit1 in a transgenic mouse lung cancer model driven by a G12D Kras mutation. Nit1 knockout mice (Nit1-/-) were crossed with KrasG12D/+ mice to investigate whether a G12D Kras mutation and Nit1 inactivation interact to promote or inhibit the development of NSCLC. We found that lung tumorigenesis was suppressed in the Nit1-null background (Nit1-/-:KrasG12D/+). Micro-CT scans and …


Steroid Binding To Autotaxin Links Bile Salts And Lysophosphatidic Acid Signalling, Willem-Jan Keune, Jens Hausmann, Ruth Bolier, Dagmar Tolenaars, Andreas Kremer, Tatjana Heidebrecht, Robbie P. Joosten, Manjula Sunkara, Andrew J. Morris, Elisa Matas-Rico, Wouter H. Moolenaar, Ronald P. Oude Elferink, Anastassis Perrakis Apr 2016

Steroid Binding To Autotaxin Links Bile Salts And Lysophosphatidic Acid Signalling, Willem-Jan Keune, Jens Hausmann, Ruth Bolier, Dagmar Tolenaars, Andreas Kremer, Tatjana Heidebrecht, Robbie P. Joosten, Manjula Sunkara, Andrew J. Morris, Elisa Matas-Rico, Wouter H. Moolenaar, Ronald P. Oude Elferink, Anastassis Perrakis

Gill Heart & Vascular Institute Faculty Publications

Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors …


Endothelial To Mesenchymal Transition (Endomt) In The Pathogenesis Of Human Fibrotic Diseases., Sonsoles Piera-Velazquez, Fabian A. Mendoza, Sergio A. Jimenez Apr 2016

Endothelial To Mesenchymal Transition (Endomt) In The Pathogenesis Of Human Fibrotic Diseases., Sonsoles Piera-Velazquez, Fabian A. Mendoza, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Fibrotic diseases encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis, sclerodermatous graft versus host disease, nephrogenic systemic fibrosis, and IgG₄-associated sclerosing disease, as well as numerous organ-specific disorders including radiation-induced fibrosis, and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrous tissue macromolecules in affected organs leading to their dysfunction and ultimate failure. The pathogenesis of fibrotic diseases is complex and despite extensive investigation has remained elusive. Numerous studies have identified myofibroblasts as the cells …


Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton Apr 2016

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …


Proceedings Of The Third Annual Deep Brain Stimulation Think Tank: A Review Of Emerging Issues And Technologies, P. Justin Rossi, Aysegul Gunduz, Jack Judy, Linda Wilson, Andre Machado, James J Giordano, W. Jeff Elias, Marvin A. Rossi, Christopher L. Butson, Michael D. Fox, Cameron C. Mcintyre, Nader Pouratian, Nicole C. Swann, Coralie De Hemptinne, Robert E. Gross, Howard J. Chizeck, Michele Tagliati, Andres M. Lozano, Wayne Goodman, Jean-Philippe Langevin, Ron L. Alterman, Umer Akbar, Greg A. Gerhardt, Warren M. Grill, Mark Hallett, Todd Herrington, Jeffrey Herron, Craig Van Horne, Brian H. Kopell, Anthony E. Lang Apr 2016

Proceedings Of The Third Annual Deep Brain Stimulation Think Tank: A Review Of Emerging Issues And Technologies, P. Justin Rossi, Aysegul Gunduz, Jack Judy, Linda Wilson, Andre Machado, James J Giordano, W. Jeff Elias, Marvin A. Rossi, Christopher L. Butson, Michael D. Fox, Cameron C. Mcintyre, Nader Pouratian, Nicole C. Swann, Coralie De Hemptinne, Robert E. Gross, Howard J. Chizeck, Michele Tagliati, Andres M. Lozano, Wayne Goodman, Jean-Philippe Langevin, Ron L. Alterman, Umer Akbar, Greg A. Gerhardt, Warren M. Grill, Mark Hallett, Todd Herrington, Jeffrey Herron, Craig Van Horne, Brian H. Kopell, Anthony E. Lang

Neuroscience Faculty Publications

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and …


Dcc Mediates Functional Assembly Of Peripheral Auditory Circuits., Young J Kim, Sheng-Zhi Wang, Stephen Tymanskyj, Le Ma, Huizhong W Tao, Li I Zhang Apr 2016

Dcc Mediates Functional Assembly Of Peripheral Auditory Circuits., Young J Kim, Sheng-Zhi Wang, Stephen Tymanskyj, Le Ma, Huizhong W Tao, Li I Zhang

Department of Neuroscience Faculty Papers

Proper structural organization of spiral ganglion (SG) innervation is crucial for normal hearing function. However, molecular mechanisms underlying the developmental formation of this precise organization remain not well understood. Here, we report in the developing mouse cochlea that deleted in colorectal cancer (Dcc) contributes to the proper organization of spiral ganglion neurons (SGNs) within the Rosenthal's canal and of SGN projections toward both the peripheral and central auditory targets. In Dcc mutant embryos, mispositioning of SGNs occurred along the peripheral auditory pathway with misrouted afferent fibers and reduced synaptic contacts with hair cells. The central auditory pathway simultaneously exhibited similar …


The Changing Roles And Reputations Of Dais In Rural Uttarakhand: An Investigation Into The Maternal Health Services Of Villages In Okhalkanda Block In Nainital, Jenna Davis Apr 2016

The Changing Roles And Reputations Of Dais In Rural Uttarakhand: An Investigation Into The Maternal Health Services Of Villages In Okhalkanda Block In Nainital, Jenna Davis

Independent Study Project (ISP) Collection

The dai, once a prominent figure in Indian maternal health, now faces marginalization as the government of India adopts the goal of universal institutional delivery. Under pressure from international discourse that Skilled Birth Attendants (SBAs) were more effective at lowering Maternal Mortality Rate (MMR) than Traditional Birth Attendants (TBAs) like dais (World Health Organization), dai training was discontinued and left in the hands of NGOs, while concurrently women and ASHAs were monetarily incentivized for every institutional birth (Park, 419). Yet in rural, isolated, or hilly areas like Okhalakanda block in Uttarakhand, institutional delivery is a long way from universal—only …


Low Radiation Dose Calcium Scoring: Evidence And Techniques, Kaitlin B. Baron, Andrew D. Choi, Marcus Y. Chen Apr 2016

Low Radiation Dose Calcium Scoring: Evidence And Techniques, Kaitlin B. Baron, Andrew D. Choi, Marcus Y. Chen

Medicine Faculty Publications

Coronary computed tomography (CT) allows for the acquisition of thin slices of the heart and coronary arteries, which can be used to detect and quantify coronary artery calcium (CAC), a marker of atherosclerotic cardiovascular disease. Despite the proven clinical value in cardiac risk prognostication, there remain concerns regarding radiation exposure from CAC CT scans. There have been several recent technical advancements that allow for significant radiation dose reduction in CAC scoring. This paper reviews the clinical utility and recent literature in low radiation dose CAC scoring.


Endothelial To Mesenchymal Transition (Endomt) In The Pathogenesis Of Systemic Sclerosis-Associated Pulmonary Fibrosis And Pulmonary Arterial Hypertension. Myth Or Reality?, Sergio A. Jimenez, Sonsoles Piera-Velazquez Apr 2016

Endothelial To Mesenchymal Transition (Endomt) In The Pathogenesis Of Systemic Sclerosis-Associated Pulmonary Fibrosis And Pulmonary Arterial Hypertension. Myth Or Reality?, Sergio A. Jimenez, Sonsoles Piera-Velazquez

Department of Dermatology and Cutaneous Biology Faculty Papers

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells …


Investigating The Role Of The Basic Helix-Loop-Helix Transcription Factor Mist1 In Pancreatic Diseases, Anju Karki Apr 2016

Investigating The Role Of The Basic Helix-Loop-Helix Transcription Factor Mist1 In Pancreatic Diseases, Anju Karki

Open Access Dissertations

Acinar cells of the exocrine pancreas are dedicated to synthesize, package and secrete immense quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Dysregulation of enzyme secretion in acinar cells can give rise to exocrine diseases including acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis—events that can transition into the earliest stages of pancreatic ductal adenocarcinoma (PDAC). The focus of this thesis is to interrogate transcriptional regulatory networks that are susceptible to AP and the role that these networks play in acinar cell and exocrine pancreas responses. The …


Influence Of The 3d Microenvironment On Glioblastoma Migration And Drug Response, Ruth Marisol Herrera Perez Apr 2016

Influence Of The 3d Microenvironment On Glioblastoma Migration And Drug Response, Ruth Marisol Herrera Perez

Open Access Dissertations

Glioblastoma (GBM) is a highly invasive brain cancer characterized by poor prognosis. Despite significant efforts by the basic and clinical research community our understanding of GBM progression and recurrence has been incremental. Improvements in therapeutic response have been dismal, and GBM continues to be the deadliest tumor of the central nervous system, with patient average survival rate of 12 months. Synergistic relationships that the tumor cells establish with the brain microenvironment have been proven fundamental for successful tumor progression and maintenance. Yet, many in vitro GBM studies are performed in formats that fail to recapitulate the most essential component of …


Neonatal Abstinence Syndrome: Pharmacologic Strategies For The Mother And Infant., Walter K. Kraft, Megan W. Stover, Jonathan M. Davis Apr 2016

Neonatal Abstinence Syndrome: Pharmacologic Strategies For The Mother And Infant., Walter K. Kraft, Megan W. Stover, Jonathan M. Davis

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem. In particular, in utero opioid exposure can result in neonatal abstinence syndrome (NAS) which is a serious condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the approach to the pregnant mother and neonate with prenatal opiate exposure. Although the cornerstone of prenatal management of opioid dependence is opioid maintenance therapy, the ideal agent has yet …


Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth Apr 2016

Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.

STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.

RESULTS: Annualized GFR change in subjects …