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Novel Mediators Of The Blood Pressure Response To Acute Psychosocial Stress In Health And Disease, Brandon Fox Jan 2018

Novel Mediators Of The Blood Pressure Response To Acute Psychosocial Stress In Health And Disease, Brandon Fox

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Psychosocial stress occurs in response to threatening or uncertainty-provoking stimuli and triggers a complex physiological reaction that facilitates survival and adaptation. In the cardiovascular system, acute psychosocial stress elicits a rapid increase in blood pressure, and importantly, cumulative exposure to psychosocial stress is a risk factor for cardiovascular disease. The present studies examined the impact of psychosocial stress on the cardiovascular system in both health and disease. Circulating endothelin-1 (ET-1) levels are induced by psychosocial stress. We hypothesized that endothelium-derived ET-1 contributes to the pressor response to stress via activation of the endothelin A (ETA) receptor. Vascular endothelium-specific ET-1 knockout …

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The Effect Of Mitochondrial-Derived Ros On Calcium Handling And Cardiac Function In Heart, Kah Yong Goh Jan 2018

The Effect Of Mitochondrial-Derived Ros On Calcium Handling And Cardiac Function In Heart, Kah Yong Goh

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Mitochondria are abundantly present in metabolic active organs such as the heart. The presence of mitochondria are crucial to provide energy in the form of ATP, regulate calcium handling, facilitate cell fate, and are involved in metabolic modulation. In the process of generating ATP through oxidative phosphorylation, mitochondria produce reactive oxygen species (ROS) as a side product. In the heart, mitochondria is a major source of ROS. Under normal conditions, ROS are kept at a physiologically relevant and healthy level. Unfortunately, excessive ROS levels during pathological states, such as pressure overload heart failure, appears as a threat to the whole …

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Centrifugal Microfluidics For Label-Free Isolation Of Leukocytes Subpopulations From Whole Blood, Yuxi Sun Jan 2018

Centrifugal Microfluidics For Label-Free Isolation Of Leukocytes Subpopulations From Whole Blood, Yuxi Sun

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Leukocytes carry critical information regarding the immediate immune and inflammation status of the patients. Analysis of leukocytes requires isolation from blood since the leukocytes only consist <1% of all blood cells. Commonly used isolation processes exploit physical or biochemical differences between different cell types to enable separations. Current isolation methods inevitably subject cells to physical or biochemical stress that can activate leukocytes and change their natural state. Thus, information contained within isolated leukocytes is a combination of the natural state of the cell and an artifact of the isolation process. Microfluidics which takes advantage of scaling effects within microscale structures can ensure rapid and gentle alternatives to conventional isolation methods and is ideal for sorting, and analysis of cells and particles. The precise control of flow/particles and scaling effects of microfluidics have been applied for blood cells sorting and isolation. However, the limited processing capability and throughput as well as complex fabrication and operations have hampered widespread adoption of these approaches for replacement of conventional methods. My goal was to develop a simple yet powerful microfluidic tool that enables rapid separation of leukocytes while ensuring sufficient throughput, and minimizing isolation process induced activation without the need any sample pre-processing. This project is divided into two specific aims: i) to miniaturize the conventional density gradient centrifugation using centrifugal microfluidics for PBMC isolation and evaluate separation efficiency and activation status of isolated cells in comparison to conventional techniques; ii) develop new approach for PBMC sorting using microfluidic phase partitioning to enable separation of cells based on differences in cell surface energy. For specific aim 1, PBMCs were isolated based on differences in densities using microfluidic density gradient centrifugation. We show that PBMCs can be isolated from 100µl whole blood within 5 minutes. Evaluation of leukocyte activation via profiling of expression of surface integrins and chemokine receptors shows that our microfluidic approach significantly reduced PBMC activation in comparison to conventional isolation approaches. In specific aim 2, we sought to isolate cells based on differenced in surface energy using two-phase partitioning of dextran (DEX) and polyethylene glycol (PEG). Proof of concept demonstrations was accomplished using with polystyrene and silicon dioxide microbeads which represent a mixture of white blood cells and red blood cells. The DEX and PEG mixtures were introduced into a circular channel and phase separated under centrifugal force into unique DEX and PEG phases. The bead mixture was isolated via differences in their affinity to the two phases.

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Female Somatic Spirituality In Post-Tridentine Art: Rutilio Manetti's St. Catherine Of Siena Drinking From The Side Wound Of Christ, Kristen Jeannine Mcarthur Jan 2018

Female Somatic Spirituality In Post-Tridentine Art: Rutilio Manetti's St. Catherine Of Siena Drinking From The Side Wound Of Christ, Kristen Jeannine Mcarthur

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This thesis presents a study of a newly discovered and previously unstudied painting of St. Catherine of Siena by Rutilio Manetti (1620s-1630s), which features a seemingly unique iconography. Based on the fifteenth-century hagiographic accounts, it identifies the subject matter and properly retitles the work, St. Catherine of Siena Drinking from the Side Wound of Christ. Contextualizing the work within its historical moment, this thesis shows that the artist navigates post-Tridentine rules of decorum in creating an image which celebrates women’s religious tradition and reasserts their spiritual authority during a time in which such traditions and authority were discouraged by the …

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Neuropeptide Y Cells Regulate Anxiety Behavior, Katelynn Corder Jan 2018

Neuropeptide Y Cells Regulate Anxiety Behavior, Katelynn Corder

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Dysregulation of the GABAergic system has long been implicated in anxiety disorders. Classic anxiolytic drugs, such as benzodiazepines, increase GABAergic transmission by modulating GABA¬A receptors, relieving anxiety symptoms. However, these treatments are not always effective and are often accompanied by negative side effects. Glutamate decarboxylase (GAD) is the enzyme responsible for producing GABA. Recent studies have shown that when the isoform GAD67 is reduced in specific brain regions or GABAergic subtypes, differential anxiety effects were found. These studies suggest that targeting specific GABAergic cell subtypes may provide a more effective treatment for anxiety disorders. Neuropeptide Y (NPY) is an abundant …

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Tutoring Video Compositions: A Model Of Adaptation, Teresa Mckinney Davis Jan 2018

Tutoring Video Compositions: A Model Of Adaptation, Teresa Mckinney Davis

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With the availability and ease-of-use of recording software on mobile phones, video essays are more accessible for composition classrooms. As these assignments are increasingly used, writ-ing centers are addressing the need for the ability to tutor video compositions. This article and conference presentation explore the foundational practices of directive and non-directive tutor-ing, examining how they can be adapted to working with video. More specifically, I argue that tutors can adapt existing theory and training to maintain a collaborative method when working with digital writing, without the need for specialized technology or technical training.

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Immune Modulation Of Pain And Recovery Via Diet, Stacie Totsch Jan 2018

Immune Modulation Of Pain And Recovery Via Diet, Stacie Totsch

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Chronic pain is the most common disability in the United States. Additionally, one out of three adults in America are obese and obesity and pain are often comorbid. Obesity is an inflammatory state due to the release of pro-inflammatory mediators from adipose tissue. Generally, obesity is a result of a poor-quality diet. Specific dietary components and patterns are independent activators of the immune system and can exacerbate the obesity-induced inflammatory state. It is known that immune system activation is a critical aspect in the development and progression of many chronic pain conditions. To address a general lack of preclinical investigations …

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Reaching Consensus On Global Health Nursing Competencies For Baccalaureate Nursing Education In The United States: A Delphi Method Study, Herica Maria Torres-Alzate Jan 2018

Reaching Consensus On Global Health Nursing Competencies For Baccalaureate Nursing Education In The United States: A Delphi Method Study, Herica Maria Torres-Alzate

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The purpose of this study was to reach consensus among experts on global health competencies for baccalaureate nursing students in the United States. A Nursing Global Health Competencies Framework (NGHCF) was created to guide identification of the domains and competencies for BSN nursing education. A three-round modified Delphi study intersected with a mixed methods research approach to reach consensus from experts in global health on essential global health competencies in nursing. The first phase revised the original list of competencies based on: (a) qualitative responses to the surveys conducted by Wilson et al. (2012), Ventura et al. (2014), and Warren …

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Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner Jan 2018

Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner

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Loss of NF1 in different developmental and cellular contexts leads to unique physiological outcomes due to loss of neurofibromin function, including embryonic lethality, sporadic cancers, and the genetic disorder NF1. Neurofibromin acts as a tumor suppressor by modulation of RAS signaling, with other functions of this multi-domain protein being less clear. Even within the monogenic disorder of NF1, the clinical heterogeneity and mutational spectrum are immense, revealing the complexity underlying this disorder. There is a huge urgency and need for NF1 therapeutic treatments, and the same urgency to develop in vivo models to better understand NF1 that can be utilized …

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Synaptic Mechanisms Underlying The Integration Of Adult-Generated Neurons In The Dentate Gyrus, Ryan Vaden Jan 2018

Synaptic Mechanisms Underlying The Integration Of Adult-Generated Neurons In The Dentate Gyrus, Ryan Vaden

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The dentate gyrus is a region in the adult brain where new neurons continue to be generated throughout life. While most adult-generated neurons undergo apoptosis within the first few weeks of maturation, a fraction survives and integrates into the existing circuit. It is well established that γ-aminobutyric acid (GABA) receptor-mediated mechanisms contribute to the activity-dependent regulation of adult-neurogenesis. GABAergic interneurons regulate stem cell quiescence, progenitor proliferation, and the synaptic integration of newborn neurons, however the synaptic interactions underlying integration are not fully understood. Furthermore, the impact of adult-generated neurons integrating into the existing circuit is not completely known. The collective …

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Clinical And Histomorphometric Outcomes Following The Use Of Small Versus Large Particle Sized Bone Allografts In Ridge Preservation Procedures: A Randomized Clinical Trial, Gentiane Valiquette Jan 2018

Clinical And Histomorphometric Outcomes Following The Use Of Small Versus Large Particle Sized Bone Allografts In Ridge Preservation Procedures: A Randomized Clinical Trial, Gentiane Valiquette

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Alveolar ridge preservation at the time of tooth extraction is a commonly performed procedure as it significantly minimizes ridge resorption and allows for more optimal implant placement. The amount of new vital bone has been shown to vary with the use of different types of bone replacement grafts, however, the effect of bone graft particle size on the outcomes following ridge preservation has not been elucidated in the scientific literature. The present randomized clinical trial compared clinically, radiographically and histomorphometrically the use of small- (0.25-1.0mm) versus large- (1.0- 2.0mm) sized particle mineralized cortico-cancellous bone freeze-dried bone allografts (FDBAs) in ridge …

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Endothelialization Of Microchannels In A Three Dimensional Breast Cancer Tumor Surrogate Model, Derek Van Vessem Jan 2018

Endothelialization Of Microchannels In A Three Dimensional Breast Cancer Tumor Surrogate Model, Derek Van Vessem

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Drug discovery and testing commonly employs two dimensional (2D) human cell line monolayers for lead compound identification before becoming a candidate therapy to be studied in animal models. Culturing cells in 2D produces a homogenous disbursement of nutrients and anticancer-therapeutics resulting in a response specific to 2D that does not necessarily translate to a three dimensional (3D) response. This method unfortunately distorts the in vivo human drug response. The lack of physiologic dimensionality in 2D cell monolayers distort cellular responses relative to 3D systems that can be attributed to minimal drug approvals. Oncology drugs are the least successful with only …

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Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo Jan 2018

Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo

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Background: There are nearly 3.5 million breast cancer survivors in the U.S., and approximately 10% are diagnosed prior to age 45 and considered “young.” The overall five-year survival rate for breast cancer survivors is approaching 90%. Living longer, many breast cancer survivors are at risk for developing cardiovascular disease due to cancer treatment, such as anthracyclines and/or trastuzumab. This study’s purpose was to examine cardiovascular disease risk, measured using excess heart age, among young breast cancer survivors. Methods: A retrospective, two-year longitudinal design was used to review electronic medical records of breast cancer survivors diagnosed between 30 and 44 years …

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Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb Jan 2018

Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb

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Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …

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Identification Of Molecular Regulators Of Morphogenesis During Early Development Of Xenopus, Ivan Popov Jan 2018

Identification Of Molecular Regulators Of Morphogenesis During Early Development Of Xenopus, Ivan Popov

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During embryonic development of all animal species, dramatic changes in morphology occur to transform a single-celled zygote into a well-organized adult body that contains different organs positioned in stereotypical ways for the species. The processes that shape tissues and organs are called morphogenesis, and gastrulation is the first morphogenetic process in embryogenesis. During gastrulation, three germ layers are specified and a set of regionally specific cell movements act in concert to position these germ layers for proper establishment of future body plan of the developing animal. Although factors regulating cell lineage specification have been studied extensively, the molecular machinery controlling …

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Calcium Signaling And Regulation Of Ecdysteroid Molting Hormone Production In Y-Organs Of The Blue Crab (Callinectes Sapidus), Megan Elizabeth Roegner Jan 2018

Calcium Signaling And Regulation Of Ecdysteroid Molting Hormone Production In Y-Organs Of The Blue Crab (Callinectes Sapidus), Megan Elizabeth Roegner

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In the blue crab (Callinectes sapidus), molting, and subsequent incremental growth, is triggered by the release of molting hormones, or ecdysteroids, from paired endocrine glands termed Y-organs. The method that triggers the increase in ecdysteroid release before molting is not fully resolved, but previous evidence suggests a calcium (Ca2+) signal may be involved. The goal of this research is to better understand the role Ca2+ signaling plays in blue crab molt hormone production. The first part of my dissertation focused on the Ca2+ regulatory protein sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), which removes Ca2+ to the ER after a Ca2+ influx. …

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Effects Of Stored Red Blood Cells On The Components Of The Lung-Capillary Membrane, Kaitlyn S. Ryan Jan 2018

Effects Of Stored Red Blood Cells On The Components Of The Lung-Capillary Membrane, Kaitlyn S. Ryan

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Trauma is the leading cause of death for Americans between the ages of 1 and 44. Implementation of massive transfusion protocols has improved early mortality due to traumatic hemorrhage; however, long-term complication rates associated with hemorrhagic shock remain high due to the development of multiple organ failure. In particular, resuscitation with large volumes of stored red blood cells (RBC) introduces high concentrations of free heme, which contributes to the development of acute lung injury (ALI) after trauma. Angiopoietin-2 (Agpt-2) is a mediator of trauma-related lung injury, but the effect of RBC storage-derived free heme on Agpt-2 regulation is unknown. The …

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The Contribution Of Mitochondrial Genetic Background To Glucose Metabolism And Insulin Sensitivity In Vivo, Melissa June Sammy Jan 2018

The Contribution Of Mitochondrial Genetic Background To Glucose Metabolism And Insulin Sensitivity In Vivo, Melissa June Sammy

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It has been observed that the risk of developing diabetes increases with age as well as among certain races, most notably African Americans and Hispanic Americans who are almost two times as likely to develop perturbed glucose metabolism compared to Caucasian Americans. Interestingly, there are distinct mitochondrial DNA polymorphisms that distinguish people of different races and thus may contribute to differential susceptibility to diseases of glucose metabolism. To test the hypothesis that the mitochondrial DNA (mtDNA) contributes to glucose metabolism and insulin sensitivity, two strains of mice were used with distinct mtDNA sequences namely, C57BL6/J and C3H/HeN as well as …

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Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston Jan 2018

Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston

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Healthy individuals typically have a diurnal rhythm in sodium (Na+) excretion, with levels higher during the daytime and lower at nighttime. While the mechanism behind this rhythm is not yet fully understood, molecular clock genes such as Bmal1 may contribute to the diurnal variation in urinary Na+ excretion (UNaV). Endothelin-1 (ET-1) is a peptide that aids in the regulation of Na+ balance through activation of the endothelin B (ETB) receptor. Although the ETB receptor has been shown to play an important role in promoting natriuresis, whether this varies according to time of day is unknown. This dissertation examines the role …

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Risk Factors Associated With Multiple Myeloma, Stephen Gragg Jan 2018

Risk Factors Associated With Multiple Myeloma, Stephen Gragg

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Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cells accumulate in the bone marrow, leading to the formation of lytic bone lesions, hypercalcemia, anemia, renal insufficiency, and immunosuppression. It develops from a pre-malignant condition known as monoclonal gammopathy of undetermined significance (MGUS), which is prevalent in up to 3% of White populations over the age of 50 years, and twice that in Black populations. Although much progress has been made toward understanding the large scale genomic aberrations that facilitate the formation of MGUS clones and the various copy-number variations and mutations that trigger the development of MM, …

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Role Of Diminished Pulsatility From Continous Flow Ventricular Assist Devices On Small Vessel Endothelial Dysfunction, Thomas Haglund Jan 2018

Role Of Diminished Pulsatility From Continous Flow Ventricular Assist Devices On Small Vessel Endothelial Dysfunction, Thomas Haglund

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Ventricular assist devices (VADs) are standard therapy for patients with advanced heart failure that is refractory to medical therapy. VADs can be categorized as pulsatile flow VADs (PF-VADs) and continuous flow VADs (CF-VADs). Both PF-VADs and CF-VADs are similarly effective in providing hemodynamic benefit and improving the quality of life and functional capacity of patients. CF-VADs are preferred over the PF-VADs due to advantages such as compact size, reliability, energy efficiency, installation and operation. However, CF-VAD support results in non-physiological diminished arterial pressure and flow pulsatility. Using the endothelial cell culture model (ECCM), we previously established that diminished pulsatility resulted …

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Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib Jan 2018

Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib

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Two pathological hallmarks define Parkinson disease (PD) including dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) and accumulation of α-synuclein insoluble inclusions, called Lewy pathology, in surviving neurons. LRRK2 (encoding Leucine-rich repeat kinase 2) and SNCA (encoding α-synuclein (α-syn)) are two major genes linked to PD. Pathogenic mutations in these two genes cause autosomal dominant (AD) PD. Additionally, genetic variations in LRRK2 and SNCA are associated with increased risk of sporadic PD. Cellular and animal studies using preformed α-syn fibrils (PFF) demonstrate that the fibrils can be internalized by neurons and act as seeds that can recruit and corrupt endogenously …

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Prohealing Multifunctional Endothelium Nanomatrix Coated Stents, Grant Alexander Jan 2018

Prohealing Multifunctional Endothelium Nanomatrix Coated Stents, Grant Alexander

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Cardiovascular disease is currently the number one cause of death in the United States, and indeed, worldwide. Stents are the most commonly implanted devices used to treat cardiovascular disease. Bare metal stent use remains limited by relatively high rates of in-stent restenosis, a re-narrowing of the artery after stent deployment. Restenosis within stents is a result of neointimal proliferation of smooth muscle cells and the accom-panying extracellular matrix deposition in response to vessel injury. To address this, drug-eluting stents have been developed to reduce restenosis; however, difficulties with late stent thrombosis, inflammation, and poor re-endothelialization remained. Thus, alt-hough numerous approaches …

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Collecting Duct Nos1 Activation Is Necessary For Increased Glomerular Filtration Rate In Response To A High Salt Diet, John Miller Allan Jan 2018

Collecting Duct Nos1 Activation Is Necessary For Increased Glomerular Filtration Rate In Response To A High Salt Diet, John Miller Allan

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We previously reported that nitric oxide synthase-1 (NOS1) in the collecting duct (CD) is critical for maintaining fluid-electrolyte balance during high salt diet. Lack of NOS1 in the CD (CDNOS1KO) results in reduced sodium excretion, urine output, and urinary nitrite/nitrate excretion compared to male control mice after 1 day of a high salt diet (4% NaCl). By day 7 of a high salt diet, CDNOS1KO mice display significantly increased systolic blood pressure with sodium excretion returning to levels similar to control mice. Sex differences in renal sodium handling are important to consider. Female rodents possess redundant mechanisms for sodium handling …

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Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade Jan 2018

Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade

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Ovarian and triple-negative breast cancers (TNBC) are aggressive due to their dependence on Wnt/β-catenin signaling. Niclosamide, a strong inhibitor of Wnt/β-catenin signaling, is an efficacious cytotoxic agent for various cancers in vitro, including ovarian and breast cancers. However, it has cross-reactivity with mTOR, STAT3, and Notch pathways. A limitation of using the agent in animal studies involves its poor water solubility and bioavailability. This study investigates novel compounds based on the structure of niclosamide to improve specificity for the Wnt/β-catenin signaling pathway. The investigation evaluates three questions: 1) whether WNT974 inhibits Wnt/β-catenin signaling in ovarian cancer; 2) whether novel analogs …

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The Effects Of Glucose And Amino Acid Restriction On Protein Turnover And Micro-Rna Composition In The Muscle Of Rainbow Trout, Mary Neslund Latimer Jan 2018

The Effects Of Glucose And Amino Acid Restriction On Protein Turnover And Micro-Rna Composition In The Muscle Of Rainbow Trout, Mary Neslund Latimer

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Changes in nutritional status, through glucose and amino acid restriction, have the ability to augment both the protein turnover and micro-RNA (miR) composition in the skeletal muscle of rainbow trout in vitro and in vivo. In vitro, the restriction of glucose in the media for a period of 24h was able to reduce protein synthesis by 41.2% compared to control conditions. In addition, 48h of glucose restriction affected the expression of both mstn2a and igfbp5, genes involved in muscle growth dynamics and synthesis. The restriction of amino acids, specifically the amino acid methionine, in vitro was able to reduce the …

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Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert Jan 2018

Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert

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Toxic chemicals may pose an increased threat to vulnerable populations such as pregnant women and their unborn fetuses. The halogen bromine has numerous industrial utilities that include flame retardant, pharmaceutical, insecticide, and bleaching additive production. At room temperature, bromine is a volatile liquid. When the gas is inhaled, bromine causes exposure-dependent acute and chronic pulmonary and systemic injuries that range from mild eye and airway irritation to severe damage to the cardiopulmonary system and other organs, which can lead to death. If exposure is survived, patients still may develop reactive airway disease syndrome and pulmonary fibrosis as well as restrictive …

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Conserved Tcr Dβ Biases Cdr-B3 Content And Alters T Cell Development And Function, Michael Steven Levinson Jan 2018

Conserved Tcr Dβ Biases Cdr-B3 Content And Alters T Cell Development And Function, Michael Steven Levinson

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T cell receptor (TCR) is a surface glycoprotein found on T cells that recognizes peptides bound to major histocompatibility complex (MHC) molecules (pMHC). Each TCR is a heterodimer consisting of an alpha (α) and a beta (β) chain that are created by rearrangements of variable (V), diversity (D), and joining (J) gene segments in the thymus. The most diverse component of the β chain is its third complementarity determining region, or CDR-B3. CDR-B3 is created de novo for each individual T cell by VDJ rearrangement and together with its TCRα partner, CDR-A3, creates the center of the TCR pMHC binding …

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The Effects Of Growth Hormone In Human Melanoma Cell Lines, Ashiya Buckels Jan 2018

The Effects Of Growth Hormone In Human Melanoma Cell Lines, Ashiya Buckels

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Melanoma is less common than basal and squamous cell skin cancers, but is the most aggressive form of skin cancer. ~90% of melanomas carry a mutation in the RAS-RAF pathway, which promotes progression by constitutive activation of the extracellular sig-nal-regulated kinase (ERK) signaling cascade. BRAF inhibition is an effective line of therapy for advance melanoma, but patients often progress due to the development of several forms of treatment resistance. Therapeutic resistance often results in increased invasion and migration of the cancer into proximal and distant tissues leading to the formation of metastasis. Examination of various cancer genomics data sets using …

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Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden Jan 2018

Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden

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Mitochondrial dysfunction is considered a hallmark of cancer. Mitochondria are essential, cellular organelles that participate in processes including energy production, calcium homeostasis and steroid metabolism. Mitochondria have been more recently appreciated for their role in cellular signaling, bringing about a greater understanding of their role in many diseases including cancer. Retrograde signaling is a mechanism by which the nucleus responds to mitochondrial dysfunction by modulating its own transcriptional programs to maintain metabolic and cellular processes. Many genes have already been identified as participants in or mediators of this signaling mechanism; these include cell signaling, metabolic and structural genes as well …

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