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Full-Text Articles in Medicine and Health Sciences

Dendritic Spine Density Varies Between Unisensory And Multisensory Cortical Regions, Moazzum Bajwa Jan 2010

Dendritic Spine Density Varies Between Unisensory And Multisensory Cortical Regions, Moazzum Bajwa

Theses and Dissertations

In the brain, the dendritic spine is a point of information exchange that extends the neuronal surface on which synapses occur, as well as facilitates and stabilizes those contacts. Furthermore, dendritic spines dynamically change in shape and number in response to a variety of factors. Dendritic spine numbers are reduced in mental retardation, enhanced during development, sensory enrichment or physical exercise, or fluctuate during the reproductive cycle. Thus, for a given neuron type, it might be expected that dendritic spine number might achieve a dynamic optimum. Indeed, many studies of spine density of pyramidal neurons in sensory cortex indicate that …


Alternative Regulation Of The Alginate Algd Operon By An Activated Algb In Nonmucoid Pseudomonas Aeruginosa Is Dependent On Sigma 54, Jean Kim Jan 2010

Alternative Regulation Of The Alginate Algd Operon By An Activated Algb In Nonmucoid Pseudomonas Aeruginosa Is Dependent On Sigma 54, Jean Kim

Theses and Dissertations

Alginate overproduction by Pseudomonas aeruginosa, which causes a mucoid phenotype, is a major virulence factor associated with chronic pulmonary infections in cystic fibrosis patients. Expression of the algD operon for alginate biosynthesis requires three major regulators in association with the ECF sigma factor, σ22, in mucoid strains that are typically defective in anti-sigma factor, MucA. One such algD regulator is AlgB, a member of the NtrC family of two-component systems, which typically utilize σ54. However, neither σ54 nor the cognate sensor kinase (KinB) of AlgB are required for algD expression in such mucoid strains. I hypothesized that KinB-phosphorylated AlgB must …


Novel Cinnamic Acid-Based Dehydropolymers For Emphysema: In Vitro And In Vivo Assessment Of Their Activities, Bhawana Saluja Jan 2010

Novel Cinnamic Acid-Based Dehydropolymers For Emphysema: In Vitro And In Vivo Assessment Of Their Activities, Bhawana Saluja

Theses and Dissertations

Pulmonary emphysema is a serious worldwide illness, causing progressive and irreversible alveolar wall loss and difficulty in breathing. It is caused mostly by cigarette smoking. However, its unresolved complex and multiple pathogenic mechanisms have left this disease without effective pharmacotherapy. This project hypothesized that cinnamic acid-based dehydropolymers (DHPs), originally discovered as novel anti-coagulants, protect against emphysema through their potent triple inhibitory actions against oxidative stress, inflammation and elastase, some of the pathogenic mechanisms associated with this disease. Three in vitro inhibitory activity assays for oxidative stress, lung inflammation and neutrophil elastase (NE) were developed and used to identify the most …


The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger Jan 2010

The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger

Theses and Dissertations

We study the activity-dependent refinement of sensory systems by using the mouse retinogeniculate system as a model. Spontaneous retinal waves lead to robust excitatory post-synaptic activity in developing relay cells in the dorsal lateral geniculate nucleus (dLGN) of the thalamus and are reportedly needed to help guide the segregation of retinal inputs into eye-specific domains as well as for the pruning of extraneous retinal inputs onto single dLGN relay cells. The composition of retinally evoked post-synaptic activity activated by these retinal waves in dLGN is largely unknown, but based on our in vitro recordings, such activity seems well suited to …


Patient Ventilator Dyssynchrony: Types, Frequency And Patterns In Critically Ill Adults, Karen Mellott Jan 2010

Patient Ventilator Dyssynchrony: Types, Frequency And Patterns In Critically Ill Adults, Karen Mellott

Theses and Dissertations

Patient ventilator dyssynchrony (PVD) occurs frequently, but little is known about the types, frequency and patterns of PVD for longer than 30 minutes. Deeper levels of sedation are associated with PVD. Evaluation of ventilator graphics and the ability to identify PVD should assist clinicians to optimize patient ventilator interactions and promote earlier interventions. The purpose of this study was to identify the different types, frequency and patterns of PVD in critically ill adults and determine the effect of sedation level on PVD. Thirty medical and surgical ICU adult patients were enrolled; 27 were used for analysis. Pressure/time and flow/ time …


The Prognostic Potential Of The Epidermal Growth Factor Receptor And Nuclear Factor Kappa B Pathways And Associated Therapeutic Strategies In Patients With Squamous Cell Carcinoma Of The Head And Neck, Pamela Wirth Jan 2010

The Prognostic Potential Of The Epidermal Growth Factor Receptor And Nuclear Factor Kappa B Pathways And Associated Therapeutic Strategies In Patients With Squamous Cell Carcinoma Of The Head And Neck, Pamela Wirth

Theses and Dissertations

Little is known about the signaling pathways that contribute to treatment response in advanced stage head and neck tumors. Increased expression of epidermal growth factor receptor (EGFR) and downstream pathways such as nuclear factor kappa B (NFκB) are implicated in aggressive tumor phenotypes and limited response to therapy. This study explored the rationale for combining the proteasome inhibitor bortezomib with the EGFR inhibitor gefitinib in a subset of head and neck squamous cell carcinomas with high EGFR gene amplification. Drug responses of gefitinib and bortezomib as single agents and in combination within head and neck squamous cell carcinoma cell lines …


Antibiotic Use By Members Of The American Association Of Endodontics: A National Survey For 2009- A Follow Up From The Report In 1999, Pye Kyu Dec 2009

Antibiotic Use By Members Of The American Association Of Endodontics: A National Survey For 2009- A Follow Up From The Report In 1999, Pye Kyu

Theses and Dissertations

The purpose of this study was to determine the changes in prescribing habits of active members of American Association of Endodontics (AAE) with regards to antibiotics in comparison to the findings reported by Yingling et al. in 1999. The invitations to take the online survey were sent via email to 2593 active members. A response rate of 37.75% was obtained. It was determined to be adequate for analysis and for comparison to the results obtained by Yingling et al. Comparisons between the percentages shown in this survey and the previous survey were tested using a z-test. An ANOVA model was …


The Association Between Lead Exposure And Respiratory Health In Children, Colleen Coleman Dec 2009

The Association Between Lead Exposure And Respiratory Health In Children, Colleen Coleman

Theses and Dissertations

Purpose: The substantial impact of indoor air quality and environmental hazards in the home on one’s health has long been recognized in the field of public health. This cross-sectional study investigates the risk between home based hazards, specifically lead, and respiratory health in children. The objective of this study is to examine the extent to which children testing positive for blood lead exposure are at an increased risk for having poor respiratory health. Methods: A nationally representative sample of 977 children ages 1- 6 years was obtained from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Information from the …


Examining The Association Of Fruit And Vegetable Intake And Breast And Prostate Cancer Screening, Mark Yu Dec 2009

Examining The Association Of Fruit And Vegetable Intake And Breast And Prostate Cancer Screening, Mark Yu

Theses and Dissertations

Breast and prostate cancer incidence and mortality have been steadily decreasing. Reasons for these reductions may be related to increased rates of cancer screening and other factors such as improvements in diet, including consumption of fruits and vegetables. We wanted to determine if individuals who get screened for breast and prostate cancer are more or less likely to consume adequate servings of fruit and vegetables. A cross-sectional study using the BRFSS survey was conducted. Individuals included in this study (n=26,222), were asked about their breast or prostate cancer screening history. They were also asked about their servings per day of …


Cardiovascular Reactivity To Forgiveness In Females, Carolyn Mccrocklin Dec 2009

Cardiovascular Reactivity To Forgiveness In Females, Carolyn Mccrocklin

Theses and Dissertations

Empirical evidence exists directly relating forgiveness to physiological markers of cardiovascular health based on the manner in which individuals respond to interpersonal offenses. Extant literature has identified the harmful effects of stress in cardiovascular disease and health in general and unforgiveness has been identified as a stressor with potential implications for cardiac health. Understanding cardiac response to the stress of unforgiveness may have favorable implications for heart disease prevention and treatment in women and may prove to be beneficial in reducing allostatic load.


Community Voice: Taking It To The People, Guidelines For Conducting A Process Evaluation, Tiffany Mcghee Dec 2009

Community Voice: Taking It To The People, Guidelines For Conducting A Process Evaluation, Tiffany Mcghee

Theses and Dissertations

Background The Community Voice program is designed for African-Americans and explores key factors that can contribute to African-American infant mortality. This program was implemented in Henrico County based on Virginia Health Statistics that the White infant mortality rate average during the years of 2001-2005 was 5.3 deaths per 1,000 live births and in the same time period the infant mortality rate for African-Americans was 13.7 deaths per 1,000 live births. At the time of implementation of the program, no plans to evaluate the program had been made. Objective This evaluation was designed to develop guidelines regarding the evaluation process of …


Vitamin B6 Metabolism And Regulation Of Pyridoxal Kinase, Amit Gandhi Dec 2009

Vitamin B6 Metabolism And Regulation Of Pyridoxal Kinase, Amit Gandhi

Theses and Dissertations

Pyridoxal 5'-phosphate (PLP) is the cofactor for over 140 vitamin B6 (PLP)-dependent enzymes that are involved in various metabolic and biosynthetic pathways. Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two key enzymes that metabolize nutritional forms of vitamin B6, including pyridoxal (PL), pyridoxine (PN), and pyridoxamine (PM) to the active cofactor form, PLP. Disruption of the PLP metabolic pathway due to mutations in PNP oxidase or PL kinase result in PLP deficiency, which is implicated in several neurological pathologies. Several ingested compounds are also known to result in PLP deficiency with concomitant neurotoxic effects. How …


The 2009 H1n1 Influenza A “Swine Flu” Virus Presentation In Virginia 2009, Tammie Smith Dec 2009

The 2009 H1n1 Influenza A “Swine Flu” Virus Presentation In Virginia 2009, Tammie Smith

Theses and Dissertations

Objective: 2009 H1N1 influenza was first detected in the Northern Hemisphere in April 2009. National data have suggested that the novel influenza virus disproportionately causes severe illness in children and young adults, a somewhat different presentation from traditional seasonal flu which normally strikes hardest in the very young and older adults. This may or may not be the case in Virginia, which, if it is different, may suggest a need to alter flu prevention messages and vaccine policy as the outbreak continues through the fall 2009-10 influenza season. This report examined the early presentation of the new influenza virus in …


Client Perceptions And Working Alliance: Predictors Of Outcome?, Theresa Do Dec 2009

Client Perceptions And Working Alliance: Predictors Of Outcome?, Theresa Do

Theses and Dissertations

BACKGROUND In recent years, there has been a push to measure and monitor the quality of health care and the delivery of effective services. Substance use disorders are debilitating and in order to better understand this facet of substance abuse, it is important for organizations and providers to assess the quality of services, client satisfaction, and the relationships that exist between clients and treatment providers. PURPOSE The purpose of the study was to (1) assess the extent of the relationship between measures of client perceptions of satisfaction and treatment outcomes and (2) to assess the relationship between measures of therapeutic …


Association Between Preconception Multivitamin Use And The Risk Of Preeclampsia/High Blood Pressure In Pregnant Women, Krisandra Allen Dec 2009

Association Between Preconception Multivitamin Use And The Risk Of Preeclampsia/High Blood Pressure In Pregnant Women, Krisandra Allen

Theses and Dissertations

Gestational Hypertension and Preeclampsia are significant causes of morbidity and mortality among pregnant women and neonates. This study examined the relationship between multivitamin use and incidence of reported high blood pressure or preeclampsia using data from the 2007 Oregon State Pregnancy Risk Assessment Monitoring System (PRAMS). Overall there were n=1894 women included in the study. Women were asked two to four months after delivery to report their multivitamin or prenatal vitamin usage in the month prior to conception and were categorized as daily users, or less than daily users. The unadjusted prevalence of high blood pressure or preeclampsia was 13.4% …


Developing A Comprehensive Youth Obesity Initiative For The State Of Virginia, Jennifer Thompson Dec 2009

Developing A Comprehensive Youth Obesity Initiative For The State Of Virginia, Jennifer Thompson

Theses and Dissertations

The 2009 Virginia General Assembly Session unanimously voted to change the legislation governing the Virginia Tobacco Settlement Foundation to create the Virginia Foundation for Healthy Youth (VFHY) and incorporate childhood overweight and obesity prevention and reduction in its mission. In order to successfully meet the requirements of this legislation, VFHY needed assistance developing a strategic plan for the obesity initiative and a knowledge base to draw from. A comprehensive assessment of the status of Virginia’s childhood obesity problem was conducted, including the prevalence of the illness, the barriers existing to and the benefits to obesity prevention programs, the need for …


Use Of Oral Chemotherapeutic Medications In Non-Traditional Ambulatory Settings, Sameer Arora Dec 2009

Use Of Oral Chemotherapeutic Medications In Non-Traditional Ambulatory Settings, Sameer Arora

Theses and Dissertations

Background: Cancer is the second leading cause of death in economically developed countries. The use and availability of oral treatment for cancer has increased dramatically in the past 10 years. Few studies have described the use of oral chemotherapy in non-traditional ambulatory settings by health care professionals across different specialties. Objective: The purpose of this study is to describe the usage of oral chemotherapeutic medications in ambulatory settings. Methods: Cross sectional study of 2007 NAMCS Survey analysis involving 21,761 subjects aged 18 years and above with cancer who participated in the 2007 National Ambulatory Medical Survey (NAMCS). Main Outcome Measure: …


Association Between Obesity And Depression And Anxiety Disorders: Results From The 2008 National Health Interview Survey, Monica Gaidhane Dec 2009

Association Between Obesity And Depression And Anxiety Disorders: Results From The 2008 National Health Interview Survey, Monica Gaidhane

Theses and Dissertations

Introduction: Obesity is one of the most important medical problems in the U.S. and is considered to be an epidemic with over 30% of the population being obese. Obesity is associated with increased risk of hypertension, diabetes, cardiovascular diseases, certain cancers and a shorter life expectancy. Recent studies have shown that higher BMI levels are also significantly associated with several lifetime mental disorders such as major depressive disorder, anxiety disorders as well as panic attacks and panic disorders. Purpose: The purpose of this study was to quantify the extent to which higher BMI increased the likelihood of Depression, Anxiety Disorder …


Intimate Partner Violence And Pregnancy: Data From The Chicago Women's Health Risk Study, Anne Zehner Dec 2009

Intimate Partner Violence And Pregnancy: Data From The Chicago Women's Health Risk Study, Anne Zehner

Theses and Dissertations

Background: Intimate partner violence (IPV) during pregnancy increases the risks of adverse outcomes for both mothers and their unborn children, including maternal and fetal death. However, more research is needed to determine if IPV increases in frequency or severity during pregnancy and to determine what the risk factors are for IPV during pregnancy. Objectives: To use data from the Chicago Women’s Health Risk Study to determine (1) if abuse is more prevalent during the pregnancy period, 2) if abuse during the pregnancy period increases in frequency or severity, 3) if pregnant women who are abused are at increased risk for …


Histone Deacetylase Inhibitors And Innate Immunity In Septic Shock, Joseph Bertsche Dec 2009

Histone Deacetylase Inhibitors And Innate Immunity In Septic Shock, Joseph Bertsche

Theses and Dissertations

Innate immunity depends on pattern recognition receptors, which recognize pathogen associated molecular patterns (PAMPS), such as Toll-like receptor 4 (TLR4), which detects the gram-negative bacterial toxin, lipopolysaccharide. Engagement of TLR4 by LPS sets off a cascade ending in the activation of pro-inflammatory cytokines and interferon-β (IFN-β) which alerts the host to the infection. However, these responses can be mal-adaptive, especially in the context of bacterial sepsis, where a "cytokine storm" results in death of the host. Pharmacological modulation of these responses may therefore be a promising treatment modality. Inhibition of classic pro-inflammatory cytokines such as IL-1β and TNF-α has been …


The P600 Event-Related Potential Across Ages And Ear Conditions, Kyla Lewis Tree Dec 2009

The P600 Event-Related Potential Across Ages And Ear Conditions, Kyla Lewis Tree

Theses and Dissertations

Studying language development through event-related potentials provides specific information regarding how the brain processes specific aspects of language over time. In this study, the P600 component, a positive wave occurring approximately 600 ms post-stimulus and known for detecting syntactic errors, was specifically analyzed. Thirty children between the ages of 5 and 12 years listened to linguistically correct, syntactically incorrect, and semantically incorrect sentences in three ear conditions: monaurally to the right ear, monaurally to the left ear, and binaurally. The participants were instructed to judge the sentences to be correct or incorrect. Comparisons were then made of the latency and …


The Differences In Levels Of Job Satisfaction Burnout And Self-Efficacy Between Correctional And Community Psychologists: The Effect Of Personality And Work Environment, Allison M. Herlickson Dec 2009

The Differences In Levels Of Job Satisfaction Burnout And Self-Efficacy Between Correctional And Community Psychologists: The Effect Of Personality And Work Environment, Allison M. Herlickson

Theses and Dissertations

The purpose of the current study was to expand on research regarding levels of job satisfaction, burnout, and counselor self-efficacy within the field of psychology and particularly among correctional and community psychologists; explore the differences between correctional and community psychologists specifically in relation to levels job satisfaction, burnout, and self-efficacy; and examine difference and/or similarities in work environments and personality traits of correctional psychologists and community psychologists. The instruments used to measure job satisfaction, burnout, counselor self-efficacy, work environment, and personality were the Minnesota Satisfaction Questionnaire, Maslach Burnout Inventory, Counselor Self-Estimate Inventory, Work Environment Scale-10, and the International Personality Item …


Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett Dec 2009

Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett

Theses and Dissertations

The opioid receptors and their endogenous ligands have long been implicated in a variety of traits including addiction, impulsive behaviors and substance dependence. Using phenotypic measurements collected from the IASPSAD, data from a latent class analysis and data from a SNP array and additional genotyping assays, association and regression tests were performed to determine the effects of common SNPs encoded in the genes of the opioid receptors and ligands on various traits relating to alcohol dependence. Although only one SNP can be reported as significant for substance dependence within alcoholics, there were a few results approaching significance that may offer …


Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith Nov 2009

Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith

Theses and Dissertations

EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 …


Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney Nov 2009

Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney

Theses and Dissertations

The chemokine receptor CCR5 has been implicated in the pathogenesis of prostate cancer. A novel natural product, anibamine, was isolated and found to be a micromolar inhibitor of the receptor. Anibamine was used as a new anti-prostate cancer lead compound. To discover the pharmacophore, analogs of anibamine were designed using the “deconstruction-reconstruction-elaboration” approach and synthesized. The establishment of a stereoselective route to only one isomer was explored, to increase yield and eliminate elaborate purification procedures. Analogs were found to have anti-prostate cancer activity at levels higher than the parent compound. The molecular modeling studies of the deconstructed analogs indicate that …


Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez Nov 2009

Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez

Theses and Dissertations

The neisserial transferrin binding proteins (Tbps) comprise a bipartite system for iron acquisition from human transferrin. TbpA is a TonB-dependent outer membrane protein that forms the pore for iron internalization. TbpB is a surface-exposed lipoprotein that makes the iron-uptake process more efficient. Previous studies have shown that the genes encoding these proteins are arranged in a bicistronic operon, with the tbpB gene located upstream of tbpA. The operon is under the control of the ferric uptake regulator (Fur) protein. However, promoter elements necessary for the regulation of the operon have not been experimentally defined. In this study, putative regulatory motifs …


Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia Nov 2009

Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia

Theses and Dissertations

Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task …


Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah Nov 2009

Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah

Theses and Dissertations

Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.


Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins Nov 2009

Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins

Theses and Dissertations

This thesis investigates two separate features of nonhomologous end-joining (NHEJ) DNA repair: end processing, and DNA repair kinase signaling. DNA end processing was investigated in a mouse model of hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), a congenital neurodegenerative disease. SCAN1 is caused by a homozygous H493R mutation in the active site of tyrosyl-DNA phosphodiesterase (TDP1). To address how the H493R mutation elicits the specific pathologies of SCAN1 and to further elucidate the role of TDP1 in processing DNA end modifications, we generated a Tdp1 knockout mouse and characterized their behavior and specific repair deficiencies in extracts of embryonic fibroblasts …


Denitration In Colonic Smooth Muscle, Seemab Malick Nov 2009

Denitration In Colonic Smooth Muscle, Seemab Malick

Theses and Dissertations

Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that …