Life Sciences Commons^™

The Imperative Of Conserving California's Foothill Oak Woodlands, Lauren Phillips

Social Sciences

No abstract provided.

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

Dissertations & Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of …

Investigation Of The Structure And Dynamics Of Regioisomeric Eu³⁺ And Gd³⁺ Chelates Of Nb-Dotma: Implications For Mri Contrast Agent Design, Benjamin Charles Webber

Dissertations and Theses

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd³⁺)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd³⁺, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of …

Selected Neuropharmacology Of Resurgence, Adam D. Pyszczynski

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The reemergence of problem behavior (i.e., relapse) is a key concern in most behavioral interventions. Resurgence refers to the reappearance of a previously rewarded behavior when reward for an alternative behavior is also discontinued. It is especially relevant to the reappearance of problem behavior because many behavioral interventions discontinue reward for aberrant behavior while simultaneously rewarding an appropriate response.

Understanding the underlying neuropharmacology of behavioral phenomena such as resurgence is important because it helps elucidate the neural processes at the root of such behavior, and also has implications for pharmacotherapies. Existing information about the neuropharmacology of resurgence is scarce, but …

Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi

Electronic Thesis and Dissertation Repository

Clinical studies have demonstrated that intrauterine growth restriction (IUGR) offspring, faced with a nutritional mismatch postpartum, have an increased risk of developing the metabolic syndrome. The maternal protein restriction (MPR) rat model has been extensively studied to investigate the adverse effects of a nutritional mismatch in postnatal life of IUGR offspring. Previous studies have demonstrated that MPR leads to impaired function of the liver, an important metabolic organ. However the underlying mechanisms which predispose these offspring to the metabolic syndrome remain elusive. In the following studies, low protein diet during pregnancy and lactation led to IUGR offspring with decreased liver …

N-Acetylcysteine As A Chemoprotectant Against Ifosfamide Nephrotoxicity; From Mechanism To Prevention, Lauren Hanly

Electronic Thesis and Dissertation Repository

The chemotherapy drug ifosfamide is used in the treatment of several childhood cancers. While effective, its use in children results in a 30% incidence of nephrotoxicity, and 5% incidence of Fanconi syndrome. This late effect is caused by oxidative damage, generated by chloroacetaldehyde, a toxic metabolite of ifosfamide cytochrome P450-mediated bioactivation in the kidney tubules. N-acetylcysteine has been identified as a promising strategy to mitigate nephrotoxicity through its antioxidant and glutathione stimulating properties. Furthermore, with current use in children for acetaminophen poisoning, its clinical utility is evident. Both cell and animal models have demonstrated n-acetylcysteine’s effectiveness in mitigating ifosfamide kidney …

Impact Of Hydraulic Fracturing On Ground And Surface Water Resources, Reyna Schenck

Natural Resources Management and Environmental Sciences

The following study examines hydraulic fracturing operations in the United States in relation to groundwater contamination, withdrawals of freshwater resources, and jurisdictional authority over the activity with the purpose of producing objective analysis of research findings. With a growing population and increasing energy needs, hydraulic fracturing is expanding across the nation, as is public concern over the risks to freshwater resources. Because of the difficulty in identifying non-point sources of water pollution, a lack of legitimate water samples representing baseline conditions, and incomplete lists of chemical additives used, study results are often inconclusive as to the correlation between hydraulic fracturing …

Lower San Luis Obispo Creek Stewardship Plan, Raven Lukehart, Daniel Bohlman

Natural Resources Management and Environmental Sciences

No abstract provided.

Proton Induced X-Ray Emission Spectrometry Of Atmospheric Aerosols At Piseco Lake, Adam Margulies

Honors Theses

Chemical studies of lakes and aerosols in the Adirondack region of New York State have found evidence of environmental pollution resulting in acid rain. We obtained air samples for July and September 2012 from Piseco Lake and analyzed particulate depositions with Proton Induced X-ray Emission (PIXE) spectrometry. We detected an array of light elements, including sulfur particulates in the 0.25 - 8 μm range, possibly stemming from coal combustion in the Appalachians and Mid-West of the United States. We also found systematic errors with the accelerator charge integration system due to beam spreading after the beam passes through the target. …

Mechanism Of Ascorbate Protection Against Sepsis-Induced Capillary Blood Flow Impairment, Dan Secor

Electronic Thesis and Dissertation Repository

Sepsis is a systemic inflammatory response to an infection. The overwhelming inflammation has many deleterious effects, including cessation of capillary blood flow. This cessation may lead to organ failure and subsequent death, but the cause of cessation during sepsis is not fully understood. Ascorbate (reduced vitamin C) has been shown to restore capillary blood flow by an unknown mechanism. I hypothesized that activation of both platelets and the coagulation pathway in sepsis contributes to the cessation of capillary blood flow and that ascorbate protects against cessation by reducing platelet activation.

Using intravital microscopy in the mouse hindlimb skeletal muscle in …

Sinusoidal Endothelial Cell-Derived Extracellular Matrix Regulates Basal And Stimulated Macrophage Activation., Lauren G. Poole

College of Arts & Sciences Senior Honors Theses

Fatty liver disease, be it from alcohol (ALD), obesity (NAFLD) or other sources (e.g. viral infection), share similar mechanisms of disease progression. One potential mechanism is that altered sinusoidal endothelial cell (SEC) extracellular matrix (ECM) favors a more inflammatory phenotype in resident macrophages (i.e., Kupffer cells). Here, the hypothesis was tested that SEC-derived matrices directly affect the inflammatory response of macrophages. Methods. Transformed sinusoidal endothelial cells (TSECs) were cultured for 24 or 72 hours. Culture plates were then washed with a solution that selectively removed the cells, but preserved the ECM. Cultured macrophages (RAW 264.7 cells) were then seeded on …

Evaluation Of Colloidal Stability And Ecotoxicity Of Metal-Based Nanoparticles In The Aquatic And Terrestrial Systems, Lok R. Pokhrel

Electronic Theses and Dissertations

Intrinsic to the many nano-enabled products are atomic-size multifunctional engineered nanomaterials, which upon release contaminate the environments, raising considerable health and safety concerns. This Ph.D. dissertation is designed to investigate (i) whether metals or oxide nanoparticles are more toxic than ions, and if MetPLATE^TM bioassay is applicable as a rapid nanotoxicity screening tool; (ii) how variable water chemistry (dissolved organic carbon (DOC), pH, and hardness) and organic compounds (cysteine, humic acid, and trolox) modulate colloidal stability, ion release, and aquatic toxicity of silver nanoparticles (AgNP); and (iii) the developmental responses of crop plants exposed to Ag- or ZnO- (zinc …

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations & Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

Modeling Greenhouse Gas Emissions And Net Return Implications For Cow-Calf Producers In The Ozark Highlands, Stephen Aaron Smith

Graduate Theses and Dissertations

Cow-calf producers in the Ozark Highlands region are under continuous pressure to improve economic efficiency. Additionally, estimating greenhouse gas (GHG) emissions from cow-calf and forage production processes may become increasingly important as policy makers seek to mitigate or reduce agriculture's role in climate change. As such, this analysis had three objectives. Objective 1: Provide a model that could be used by cow-calf producers, extension agents, and researchers to evaluate GHG and net return (NR) repercussions when modifying site characteristics, production methods, and inputs. Objective 2: Develop a user guide such that the methodology for estimating cow-calf GHG emissions and NR …

Modulation Of Synaptic Transmission By Adenosine In Layer 2/3 Of The Rat Visual Cortex In Vitro, Nicholas M. Bannon

Master's Theses

No abstract provided.

Cultivating Resistance: Food Justice In The Criminal Justice System, Caitlin M. Watkins

Pitzer Senior Theses

This Senior Thesis in Environmental Analysis seeks to explore the ways in which certain food-oriented programs for incarcerated women and women on parole critically resist the Prison Industrial Complex and the Industrial Food System by securing social and ecological equity through the acquisition of food justice. It focuses on three case studies: the Crossroads’ Meatless Mondays program, Fallen Fruit from Rising Women: A Crossroads Social Enterprise, and Cultivating Dreams Prison Garden Project: An Organic Garden for Women in Prison. Each project utilizes food as a tool to build community, provide valuable skill sets of cooking and gardening, and educate women …

Mechanisms Of Cytokine-Induced Metabolic Dysfunction Of The Pancreatic Beta-Cell, Abiy Mussa Mohammed

Wayne State University Dissertations

MECHANISMS OF CYTOKINE-INDUCED METABOLIC DYSFUNCTION OF THE PANCREATIC BETA-CELL

by

ABIY MUSSA MOHAMMED

August 2013

Advisor: Dr. Anjaneyulu Kowluru

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Type I diabetes is characterized by an absolute insulin deficiency due to loss of pancreatic â-cell mass by autoimmune aggression. During the progression of the disease proinflammatory cytokines such as IL-1â, TNFá and INFã are secreted by infiltrated and activated T-cells and macrophages which ultimately damage the pancreatic â-cell. However, the signaling mechanisms involved in cytokine-induced damage are only partially understood. Phagocyte-like NADPH oxidase [NOX2] has been shown to play regulatory roles in the …

Overcoming Tumor Drug Resistance By Activating Amp-Activated Protein Kinase And Destabilizing Oncoproteins, Min Shen

Wayne State University Dissertations

Although considerable progress has been achieved in the field of cancer therapeutics, primary or acquired drug resistance remains a fundamental cause of therapeutic failure in cancer therapy. Among different mechanisms characterized that are responsible for tumor drug resistance, there is increasing evidence suggesting that dysregulation of gene expression, especially oncogene or tumor suppressor gene expression, at either gene transcription or protein synthesis level, can contribute to the drug-resistant phenotype. AMP-activated protein kinase (AMPK) is a well-known major cellular energy sensor, which negatively regulates metabolic pathways such as protein synthesis, fatty acid oxidation and glucose consumption. Activation of AMPK may suppress …

Polymeric Nanocarriers And Their Oral Inhalation Formulations For The Regional Delivery Of Nucleic Acids To The Lungs, Denise Santos Conti

Wayne State University Dissertations

Gene therapy has attracted attention in the fields of medicine, pharmacy, and bionanotechnology due to the potential for treating a large number of medically relevant diseases. Oral inhalation (OI) is a promising route for the administration of therapeutics, including small molecules and biomacromolecules, such as nucleotides, peptides, and proteins, to (locally) and through (systemically) the lungs. The use of OI is especially attractive for the delivery of nucleic acids as it provides a direct and non-invasive route for targeting the lungs. Pressurized metered-dose inhalers (pMDIs), are the most commonly used OI in treatment of lung diseases and are thus promising …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Design, Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Multifunctional Neuroprotective Drugs For The Treatment Of Parkinson's Disease: An Effort Towards The Improvement Of In Vivo Efficacy And Modulation Of Alpha Synuclein Aggregation Property Of The Neuroprotective Parent, Gyan Prakash Modi

Wayne State University Dissertations

DESIGN, SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR MODELING STUDIES OF NOVEL MULTIFUNCTIONAL NEUROPROTECTIVE DRUGS FOR THE TREATMENT OF PARKINSON'S DISEASE: AN EFFORT TOWARDS THE IMPROVEMENT OF IN VIVO EFFICACY AND MODULATION OF ALPHA SYNUCLEIN AGGREGATION PROPERTY OF THE NEUROPROTECTIVE PARENT MOLECULE (D-264)

by

GYAN PRAKASH MODI

May 2014

Advisor: Dr. Aloke K. Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Parkinson's disease (PD) is a progressive age-related neurodegenerative disorder of the central nervous system that is characterized by gradual loss of dopaminergic neurons in the substantia nigra region of the brain. The research from the past two decades in PD area …

Oligospermines For Non-Viral Sirna Delivery, Maha Elsayed

Wayne State University Theses

In this thesis, delivery systems for siRNA delivery are introduced with special attention to non-viral vectors. Many successful vectors used in vivo were reviewed. Our work focused on the effect of different architectures of oligospermine polmers on their suitability for siRNA delivery in lung cancer cells. Different archituctures showed different polyplex structures and variable transfection efficiencies. Moreover, we presented a review on nanoimprint lithography techniques with an outlook on possible biological applications in the field of gene and drug delivery.

The Effect Of Alpha-Cyclodextrin On Acute Blood Lipid And Glycemic Responses To A Fat Containg Meal, Evan Neil Fletcher

Wayne State University Theses

Obesity and hyperlipidemia have become major concerns in the United States over the past 30 years. Alpha-Cyclodextrin (á-CD), a naturally occurring soluble dietary fiber, has been shown to reduce dietary fat absorption and improve blood lipid levels in an animal model (mouse and rat) and in human studies. In the current double blind study, 34 healthy male and female participants were recruited to test if á-CD had any acute effect on blood lipid and glycemic responses to a fat containing meal. The participants received the á-CD on one occasion and a placebo the other to determine if there was any …

Toxicological Effects Of Cerium Oxide Nanoparticle Aggregates On Caenorhabditis Elegans, Steven N. Rogers

Theses, Dissertations and Capstones

Assessing the toxicity and unique reactivity of nanoparticles in biological systems has become an relevant and quickly growing area of environmental toxicology research. The broad use of nanoparticles in industrial and commercial commodities results in exposure of these nano-compounds to the environment, the ecosystems, and humans. While previous data has suggested that cerium oxide (CeO₂) nanoparticles are relatively safe to cultured cells much less is known about the potential toxicity of these materials at the organismal level. In this study we employed transgenic Caenorhabditis elegans (C. elegans) strains to assess the toxicity of CeO₂ nanoparticles under “real-world” …

Does The Use Of Varenicline For Smoking-Cessation Therapy Create Or Increase Depression In Patients Without Existing Depressive Illness?, Brett R. Brown

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of varenicline for smoking-cessation therapy creates or increases depression in patients without existing depressive illness.

STUDY DESIGN: Review of two randomized controlled trials published in 2011 and one observational cohort study published in 2009, all English language.
DATA SOURCES: Two randomized, double-blind, controlled clinical trials comparing varenicline to placebo in smoking cessation, and one observational cohort study comparing varenicline use within subjects. All articles were found using PubMed and EBSCO.

OUTCOMES MEASURED: Changes in depression was evaluated using the MontgomeryÅsberg Depression Rating Scale …

Does Nicotine Replacement Therapy Reduce The Withdrawal Symptom Of Craving, Or Urge To Smoke, In Dependent Adult Smokers During Smoking Cessation?, Theresa Dijoseph

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not nicotine replacement therapy reduces the withdrawal symptom of craving, or urge to smoke, in dependent adult smokers during smoking cessation.

STUDY DESIGN: Systematic review of three English language and peer-reviewed randomized-controlled trials published in 2009, 2010, and 2011.

DATA SOURCES: One single-blinded randomized-controlled crossover trial, one double-blinded, placebo controlled, randomized-controlled crossover trial, and one single-blinded, placebo controlled, randomized-controlled crossover trial

OUTCOMES MEASURED: Withdrawal symptoms of craving, irritability, difficulty concentrating, and restlessness were measured on a 100mm visual analog scale (VAS). Adverse effects (AEs) of mouth and …

Methylmercury Exposure Affects Risk-Taking Behaviors In Zebra Finches: Tradeoffs Between Eating And Being Eaten, Megan Elizabeth Kobiela

Dissertations, Theses, and Masters Projects

No abstract provided.

Regulation Of 7-Dehydrocholesterol Reductase By Vitamin D3, Ling Zou

Theses and Dissertations--Pharmacy

7-Dehydrocholesterol (7-DHC) is the substrate of 7-dehydrocholesterol reductase (DHCR7) in the cholesterol synthesis pathway. Keratinocytes in human skin possess the enzymes necessary for cholesterol synthesis but are also responsible for vitamin D₃ synthesis from 7-DHC by exposure to UVB irradiation. It has been well established that DHCR7 is regulated by the SREBP pathway in the regulation of cholesterol synthesis, but little is known about the regulation of DHCR7 by the vitamin D pathway. In this study, the regulation of DHCR7 activity by vitamin D was explored. Treatment of adult human epidermal keratinocyte (HEKa) cells with vitamin D₃ resulted …

Methylphenidate And Atomoxetine Treatment During Adolescence In The Spontaneously Hypertensive Rat: Mechanisms Underlying High Cocaine Abuse Liability In Attention Deficit/Hyperactivity Disorder, Sucharita S. Somkuwar

Theses and Dissertations--Pharmacy

Effects of pharmacotherapies for Attention Deficit/Hyperactivity Disorder (ADHD) on cocaine abuse liability in ADHD are not understood. Spontaneously Hypertensive Rats (SHR), an ADHD model, exhibited greater cocaine self-administration than control Wistar-Kyoto and Wistar rats. Methylphenidate, but not atomoxetine during adolescence enhanced cocaine self-administration in adult SHRs compared to controls. The mesocortical dopaminergic system, including medial prefrontal (mPFC) and orbitofrontal (OFC) cortices, is important for ADHD and cocaine addiction. Dopamine and norepinephrine transporter (DAT and NET) are molecular targets for methylphenidate, atomoxetine and cocaine action.

In the current studies, SHR, Wistar-Kyoto and Wistar were administered methylphenidate (1.5 mg/kg/day, p.o.), atomoxetine (0.3 …

My Experience Exploring The Effects Of Lead (Pb +2) Toxicity In Drosophila Melanogaster Using Sociability Interaction Testing And Microarrays At The University Of Puerto Rico-Rio Piedras In San Juan, Puerto Rico, Charlton Diaz

Honors Theses

Lead is an environmental contaminant widely dispersed throughout the world. Exposure to lead causes neurological damage in humans and may be linked to neurodevelopmental pathologies such as attention deficit hyperactivity disorder, antisocial behavior, and autistic spectrum disorders (ASD). Drosophila melanogaster (fruit flies) have been used to understand the behavioral, synaptic, and molecular changes that occur after developmental exposure to lead and to study ASD-associated pathology. Flies were exposed through the mother and until eclosion to either a lead-laced medium or a control corn-based medium and were isolated until the beginning for the behavioral studies. Sociability testing was done using a …