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Articles 1 - 30 of 60
Full-Text Articles in Medicine and Health Sciences
Investigating The Role Of Myristoylated Alanine Rich C Kinase Substrate's (Marcks's) Effector Domain In Lung And Brain Cancer Biology, Timothy D. Rohrbach
Investigating The Role Of Myristoylated Alanine Rich C Kinase Substrate's (Marcks's) Effector Domain In Lung And Brain Cancer Biology, Timothy D. Rohrbach
All ETDs from UAB
In this study, we investigated the role MARCKS's Effector Domain plays in lung and brain cancer biology. Initially, we identified that MARCKS was present in a range of lung cancer histologies including: squamous cell, adenocarcinoma, and normal lung tissues among others. In addition, lung adenocarcinoma patients with a mutation in the MARCKS gene correlated with decreased survival as determined by The Cancer Genome Atlas. In vitro studies identified that the phosphorylation status of MARCKS's Effector Domain was able to influence lung cancer radiation sensitivity. When MARCKS's Effector Domain was in a non-phosphorylated state, A549 lung cancer cell lines experienced increased …
Transcriptional Regulation Of The Human Ribosomal Rna Gene, Blake L. Atwood
Transcriptional Regulation Of The Human Ribosomal Rna Gene, Blake L. Atwood
All ETDs from UAB
The ribosome has the major role of synthesizing almost all the proteins of the cell. One of the main structural components of the ribosome are the ribosomal RNAs 18S, 28S, 5.8S and the 5S which are bound by numerous proteins to make up a fully functional unit. In the human genome there are approximately 400 copies of the rRNA gene, which contains all but the 5S rRNA in one long transcription unit. This gene is found in tandem repeats on the acrocentric arm of chromosomes 13, 14, 15, 21 and 22. It is critical that this gene is tightly regulated …
Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu
Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu
All ETDs from UAB
STAT3 signaling is a major intrinsic pathway for cancer inflammation owing to its frequent activation in malignant cells, and key role in regulating many genes crucial for inflammation in the tumor microenvironment. Persistently activated STAT3 increases tumor cell proliferation, survival, and invasion while suppressing anti-tumor immunity. Suppressor Of Cytokine Signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway, and generally function as tumor suppressors. The absence of SOCS3 in particular leads to heightened activation of the STAT3 transcription factor. In the present study, we demonstrate that genetic deletion of SOCS3 specifically in myeloid cells significantly enhances tumor growth, which …
Norepinephrine Circuits In Mediating Stress-Elicited Behavior, Hyungwoo Nam
Norepinephrine Circuits In Mediating Stress-Elicited Behavior, Hyungwoo Nam
All ETDs from UAB
Norepinephrine in the central nervous system (CNS) is a key mediator of stress-elicited behavioral and physiological adaptations. However, our understanding of central noradrenergic circuitry that regulates specific stress-elicited adaptations is incomplete. The working model for the studies described in this dissertation is that disruptions of specific noradrenergic circuits are responsible for the manifestation of distinct stress-elicited behaviors. Initially the organization of descending noradrenergic neurons with poly-synaptic collaterals to the adrenal gland and skeletal muscle was defined. These noradrenergic presympathetic-premotor neurons (PSPMNs) were distributed within the ventral locus coeruleus (LC), nucleus subcoeruleus (SubC), and the A7 cell group. Then behavioral characterization …
Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum
Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum
All ETDs from UAB
Schizophrenia is a mental illness affecting 1% of the population worldwide. Treatment options are limited for patients, due in part to the lack of understanding of the pathophysiological mechanisms of schizophrenia. In order to improve treatment, it is vital to gain a better understanding of the underlying pathology of the disorder. One region of particular interest is the nucleus accumbens (NAcc). Part of the ventral striatum, this region is thought to play a role in schizophrenia pathology for multiple reasons: afferent input of many brain regions implicated in schizophrenia is integrated here; the dopamine and glutamate systems, both known to …
Exploiting The Glioblastoma Tumor Microenvironment For Enhanced Oncolytic Herpes Simplex Virus Therapy, Tyrel Talbert Smith
Exploiting The Glioblastoma Tumor Microenvironment For Enhanced Oncolytic Herpes Simplex Virus Therapy, Tyrel Talbert Smith
All ETDs from UAB
Gliomas are the most common and fatal malignancy of the adult central nervous system. The need for new therapeutic options is clear, as standard of care therapies only extend median survival 12-14 months beyond diagnosis. Conditionally replication-competent oncolytic herpes simplex type-1 viruses (oHSV) have emerged as promising therapeutics for treating malignant gliomas. However, two factors that contribute to the dismal prognosis of malignant gliomas, immunosuppression and invasive growth, are also thought to limit virotherapeutic efficacy. We examined these factors in tumor microenvironments to explore novel strategies to treat malignant gliomas with oHSV for improved therapeutic response. In a Phase 1b …
The Role Of Ribosome Biogenesis In Exercise-Induced Skeletal Muscle Anabolism In Aging, Michael Stec
The Role Of Ribosome Biogenesis In Exercise-Induced Skeletal Muscle Anabolism In Aging, Michael Stec
All ETDs from UAB
Numerous chronic medical conditions, as well as normal aging result in a significant loss of skeletal muscle mass. This has profound effects on quality of life and can increase the risk of all-cause mortality. Currently, the most potent treatment for reversing the loss of muscle mass is resistance exercise training (RT); however, the human muscle fiber growth (hypertrophy) response to this treatment is quite variable, and older adults do not respond as favorably to this treatment as younger adults. The focus of this dissertation is to elucidate the role that ribosome biogenesis plays in regulating the RT-induced hypertrophic response. We …
Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley
Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley
All ETDs from UAB
Breast cancer remains the most frequently diagnosed cancer amongst women worldwide. Despite advances in treatment, patients with more aggressive basal-like and HER2-positive cancer experience high rates of recurrence and necessitate novel therapeutic approaches. A class of inhibitors targeted against poly (ADP-ribose) polymerases (PARP), important DNA repair proteins, are effective in cancers with a defective DNA repair response. As such, extensive preclinical and clinical research has examined their efficacy in these cancers. Although this data is promising, it is only applicable to a lim-ited patient population. The main goal of this dissertation is to expand the utility of these well-tolerated drugs …
The Effect Of Thioredoxin-Interacting Protein Induced Microrna-200 Family Members On Pancreatic Beta Cells, Stephen Filios
The Effect Of Thioredoxin-Interacting Protein Induced Microrna-200 Family Members On Pancreatic Beta Cells, Stephen Filios
All ETDs from UAB
Pancreatic beta cells secrete insulin to maintain normal blood glucose levels and allow cells of the body to use glucose. However, in diabetes, there is beta cell dysfunction and pancreatic beta cells undergo programmed cell death leading to inadequate insulin production and secretion. Thioredoxin-Interacting Protein (TXNIP) is a ubiquitously expressed protein, 46 kDa in size, which is an arrestin protein family member. Unique to this member of the arrestin family, however, is its ability to bind to, and reduce, thioredoxin. The TXNIP gene is increased in pancreatic islets more than any other gene in response to high levels of glucose. …
The Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki
The Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki
All ETDs from UAB
Human cytosolic sulfotransferases (SULTs) are a family of Phase II conjugating enzymes that facilitate the transfer of a sulfonate moiety from 3’phosphoadenosine 5’phosphosulfate (PAPS) to hydroxyl or amine groups of acceptor substrates. SULT1A1, located in many tissues throughout the human body including the liver, is important in the metabolism of many endogenous, exogenous, xenobiotic, and drug compounds. The majority of substrates for SULT1A1 are small neutral phenols including 1-naphthol and acetaminophen; however, SULT1A1 sulfates larger compounds including 17β-estradiol (E2) and raloxifene. SULT1A1 conjugates E2 with a Km of 2.3 µM and the structure of E2 is almost identical to the …
Role Of Macrophages In The Cardiomyopathy Associated With Obesity And Type 2 Diabetes, Mehak Goel
Role Of Macrophages In The Cardiomyopathy Associated With Obesity And Type 2 Diabetes, Mehak Goel
All ETDs from UAB
Obesity is a state of chronic low-grade systemic inflammation that, along with type 2 diabetes (T2D), increases the risk of developing cardiovascular disease (CVD). Despite the wealth of information on the link between macrophages and cytokines in adipose tissue and peripheral insulin resistance, their role in the pathogenesis of diabetic cardiomyopathy and cardiac diastolic dysfunction is unclear. We hypothesized that activated immune cell mediators, in particular monocytes and macrophages, are fundamental drivers of diet-induced obesity and diabetic cardiomyopathy. Herein, firstly, a diet-induced model of diabetic cardiomyopathy was developed in C57BL/6 mice by feeding a high fat diet (HFD, 45% kcal …
The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu
The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu
All ETDs from UAB
Dysregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is critically involved in the pathogenesis of multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE). Suppressor Of Cytokine Signaling (SOCS) proteins are the negative regulators of the JAK/STAT pathway. To determine the role of SOCS3 in myeloid cells in EAE, mice with conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3fl/fl) were created and tested. LysMCre-SOCS3fl/fl mice develop a severe, non-resolving atypical form of disease, characterized by lesions and extensive neutrophil and other inflammatory cell infiltrates in the cerebellum and brainstem, elevated STAT activation, elevated cytokine, chemokine and iNOS expression, and prominent …
A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown
A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown
All ETDs from UAB
In the first step in light perception, rod and cone photoreceptors convert photon absorption into an electrical impulse that is transmitted through the visual pathway. While the biochemistry and the signaling physiology have largely been defined in dark-adapted, isolated mammalian rods, there are still unanswered questions regarding photoreceptor light adaptation processes that involve extracellular components. In particular, the proteins of the interphotoreceptor matrix have not been considered in the studies of rod signaling and adaptation. This thesis details a new form of light adaptation, now known as adaptive potentiation (AP), in which extracellular components act on rods to transiently increase …
Stat4 Regulates Multiple Pathogenic Mechanisms Of Cd4 T Cells In Experimental Autoimmune Encephalomyelitis, A Model Of Multiple Sclerosis, Ian Lee Mcwilliams
Stat4 Regulates Multiple Pathogenic Mechanisms Of Cd4 T Cells In Experimental Autoimmune Encephalomyelitis, A Model Of Multiple Sclerosis, Ian Lee Mcwilliams
All ETDs from UAB
Multiple Sclerosis (MS) is an autoimmune disease whereby the host immune system fails to recognize self vs non-self and targets myelin of the central nervous system. Currently there is no permanent cure for MS and the efficacy of immune modulatory treatments often wane over time, therefore we seek to determine novel pathogenic mechanisms to target therapeutically. CD4 T cells have been found within inflammatory CNS lesions of MS patients and are believed to be important mediators of MS pathology. To study CD4 T cells in the context of MS, we use the well-defined MS mouse model experimental autoimmune encephalomyelitis (EAE). …
Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows
Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows
All ETDs from UAB
Learning and memory rely on long-lasting, experience-dependent adaptations in synaptic and non-synaptic forms of neuronal plasticity. Previous evidence implicates transcriptional and epigenetic mechanisms, including DNA cytosine methylation, as critical regulators of site-specific, Hebbian alterations in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). However, whether DNA methylation modulates cell-wide, non-Hebbian homeostatic adaptations like synaptic scaling and intrinsic plasticity (IP) is unclear. Whereas synaptic scaling involves bidirectional changes in postsynaptic receptor density in response to chronic alterations in neuronal activity, IP involves the activity-dependent attunement of passive and/or active membrane properties that govern action potential (AP) firing. This …
Innate Immunity Mechanisms In Parkinson Disease, Mark Moehle
Innate Immunity Mechanisms In Parkinson Disease, Mark Moehle
All ETDs from UAB
Parkinson disease (PD) is a late onset, progressive neurodegenerative movement disorder with cardinal symptoms of tremor at rest, bradykinesia, postural instability, and rigidity. These motor symptoms of PD are caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, despite PDs first modern observation in 1817, little is understood about the causes and molecular mechanisms behind dopaminergic neuron loss. The relatively weak understanding of pathological mechanisms has hindered the development of treatments to slow or halt the progression of PD. However, recently, mounting evidence from post-mortem, imaging, and retrospective studies suggest an important role …
Structural Implications Of P22 Bacteriophage Coat Protein A-Domain Modifications, David Samuel Morris
Structural Implications Of P22 Bacteriophage Coat Protein A-Domain Modifications, David Samuel Morris
All ETDs from UAB
Modification of virus capsids as target-specific delivery devices has become highly popularized in recent years and P22 bacteriophage has been proposed as a potential candidate for development of a targeting drug delivery system. As a proof of concept for our system, we hypothesized that the A-domain of P22 coat protein could be utilized to alter the binding affinity of virus-like procapsids for biological targets. Addition of acidic residues to the A-domain revealed that this could be accomplished through the quarternary localization of charged residues in three-dimensional space without interrogating procapsid assembly. Further manipulations implemented in vivo were performed to examine …
Gaba(A) Receptor Trafficking And Localization In Schizophrenia, Toni Marie Mueller
Gaba(A) Receptor Trafficking And Localization In Schizophrenia, Toni Marie Mueller
All ETDs from UAB
Mechanisms underlying the complex etiology of schizophrenia have long been a subject of scientific inquiry. Early investigations focused on identifying functional deficits in dopaminergic and glutamatergic neurotransmission, but evidence for disrupted GABAergic signaling has also emerged. Recent studies from our lab have identified disrupted N-glycosylation of glutamate receptor and transporter subunits and abnormal subcellular distribution of glutamate receptor subunits, suggesting a potential functional consequence of perturbed N-glycosylation in schizophrenia. N-glycosylation is the posttranslational enzymatic attachment of an oligosaccharide precursor to a protein. This modification plays a significant role in protein processing in the ER and Golgi, and is known to …
The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues
The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues
All ETDs from UAB
Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. …
The Alpha-Glucosidase Inhibitor Acarbose As A Calorie Restriction Mimetic To Modify Metabolic Outcomes In Mice, Rachel Ann Brewer
The Alpha-Glucosidase Inhibitor Acarbose As A Calorie Restriction Mimetic To Modify Metabolic Outcomes In Mice, Rachel Ann Brewer
All ETDs from UAB
Age-related diseases continue to be a leading cause of death. One of the only replicable methods proven to decrease age-related morbidity and mortality in multiple species is calorie restriction (CR). CR is difficult for human populations to implement, and has a number of associated risks and side effects. A CR mimetic could provide the healthspan- and lifespan-extending benefits of CR without the limitations. Acarbose (ACA), an α-glucosidase and α-amylase inhibitor approved to treat type 2 diabetes in humans, was recently identified as able to extend lifespan in healthy mice. The purpose of this research was to determine the effects of …
Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard
Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard
All ETDs from UAB
Transforming growth factor-β1 (TGF-β1) is one of the most abundant cytokines of the dentin-pulp complex that regulates a broad range of biological processes related to matrix synthesis and ultimately tooth formation, including secretion and mineralization of the dentin extracellular matrix (DECM). TGF-β1 mediates odontoblast cytodifferentiation from precursor dental pulp cells, being up-regulated in odontoblasts and then incorporated into the DECM as a reservoir that can be utilized in times of mechanical, chemical, or bacterial insult. Formation of the DECM is modulated by the actions of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), which include DMP-1, DSPP, BSP, SPP1, and MEPE, with …
G Protein-Coupled Inwardly-Rectifying Potassium (Girk) Chanels Mediate Entrainment Of Circadian Rhythms, Lauren Marie Hablitz
G Protein-Coupled Inwardly-Rectifying Potassium (Girk) Chanels Mediate Entrainment Of Circadian Rhythms, Lauren Marie Hablitz
All ETDs from UAB
Circadian rhythms are 24-hour cycles in biological and behavioral processes. These cycles enable an organism to predict changes in its environment, like changes in food availability and seasonality. Although endogenously driven, these rhythms can entrain or synchronize to daily changes in the environment, allowing the animal to adapt. One way entrainment occurs is shifts in circadian phase following the presentation of nonphotic, or non-light, stimuli, such as exercise, arousal, or stress at certain times of day. The molecular mechanisms underlying nonphotic entrainment are poorly understood - specifically, how nonphotic cues alter excitability within the suprachiasmatic nucleus (SCN) of the hypothalamus, …
Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward
Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward
All ETDs from UAB
A preponderance of evidence has established that obesity contributes to memory impairments in mid-age adults. Empirical evidence has revealed that diet-induced obesity contributes to memory impairments in adult rodents. Precisely how obesity disrupts memory remains an open question. Bourgeoning data indicate that molecular epigenetic mechanisms mediate the changes in gene transcription that are necessary for hippocampus-dependent memory consolidation. Epigenetic mechanisms, such as DNA methylation, stably regulate gene expression without affecting the DNA sequence. Moreover, DNA methylation of memory-related genes with in the hippocampus is indispensible for memory formation. There is recent evidence of obesity-induced aberrantions in DNA methylation both peripherally …
Caenorhabditis Elegans Sperm Chemotaxis, Hieu Dinh Hoang
Caenorhabditis Elegans Sperm Chemotaxis, Hieu Dinh Hoang
All ETDs from UAB
Survival of animal species depends on fertilization, the union of an egg and a sperm. The sperm's ability to find an egg quickly allows it to pass on male genetic material. It is challenging to record sperm targeting or guidance efficiency and motility in utero. We use the Caenorhabditis elegans model organism to study sperm guidance, primarily because its epidermis is transparent, allowing the observation of live fluorescent sperm in the hermaphrodite uterus. Using genome-editing techniques, genetic analyses, fluorescent microscopy, and mass spectrometry, we aim to address the following two questions: how hermaphrodites regulate sperm motility in the uterus, and …
Changes In Gene Expression During Nitrogen Starvation Are Mediated By Targeted Degradation Of Translation And Mrna Decay Factors In Saccharomyces Cerevisiae, Shane Patrick Kelly
Changes In Gene Expression During Nitrogen Starvation Are Mediated By Targeted Degradation Of Translation And Mrna Decay Factors In Saccharomyces Cerevisiae, Shane Patrick Kelly
All ETDs from UAB
Autophagy is the cellular mechanism of recruitment and decay of cytoplasmic molecules, proteins, and organelles that are obsolete for a particular growth condition. Autophagic degradation is distinct from proteasomal degradation by the formation of a de-novo double membrane which engulfs its cargo to be delivered for degradation to the yeast vacuole. Once thought to be only a general phenomenon of bulk decay, several autophagic pathways have demonstrated selectivity. In the following work we show that during nitrogen starvation (a potent inducer of autophagy) in the yeast Saccharomyces cerevisiae, a subset of translation factors are degraded selectively and rapidly. We go …
Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer
Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer
All ETDs from UAB
The increasing prevalence of metabolic syndrome, diabetes, atherosclerosis, and many other diseases only recently associated with aberrant metabolism, have led to a de-mand for clinical assays to determine a patient’s mitochondrial health. With the rapidly growing interest in personalized medicine, such an assay would ideally be able to capture the metabolic changes associated with oxidative stress, inflammation, and therapy of a patient in a swift and non-invasive manner. Short of tissue biopsies, this burgeoning field of Translational Bioenergetics has had minimal success in obtaining sufficient human cells and the means to assess them both accurately and swiftly. The purpose of …
Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski
Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski
All ETDs from UAB
Mineralization is a tightly controlled bi-phasic process that occurs when crystals of calcium and phosphate (Pi) are laid down within the extracellular matrix. However, the molecular networks regulating the initiation and progression of this process have not been well characterized. Pi, as one of the components of mineral crystals and a signaling molecule that regulates expression of mineralization-related genes, is essential to the mineralization process. In our studies, we discovered a novel function for Pi in this process: Pi is sufficient to induce secretion of matrix vesicles, which support the initiation of mineralization. Furthermore, we determined that this induction is …
An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis
All ETDs from UAB
Nephronophthisis (NPHP) is a ciliopathy with diverse clinical features likely caused by genetic modifiers. To identify NPHP modifiers, a screen was conducted on nphp-4(tm925) mutant C. elegans to reveal mutations that exacerbate the NPHP ciliary defects. Ten loci were generated, five of which have now been identified. Three are mutations in ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. As in osm-3 null mutants, nphp-4(tm925);osm-3(yhw66) mutants lack distal segments, are dye-filing defective (Dyf), and have osmotic avoidance defects (OSM). The osm-3(yhw66) mutant alone …
Decoding Nf1 Intragenic Copy-Number Changes, Meng-Chang Hsiao
Decoding Nf1 Intragenic Copy-Number Changes, Meng-Chang Hsiao
All ETDs from UAB
Genomic rearrangements may cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements have been proposed such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR). However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number changes (CNCs) remains understudied. Furthermore, only few studies resolved these pathogenic alterations at the nucleotide-level. Accordingly, our aim was to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as …
Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull
Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull
All ETDs from UAB
Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in the catabolism of heme, which is released by necrotic cells in injured tissue. HO-1 expression is protective in cardiac and renal injury because it coordinates the degradation of pro-oxidant heme with the generation of equimolar quantities of iron (Fe2+) and the cytoprotective mole-cules carbon monoxide and biliverdin. While many studies have demonstrated that HO-1 expression is protective in numerous disease states, relatively few have examined the specific cellular compartment(s) through which HO-1 expression confers its protective effects. Our objective was to define the cellular compartments in which HO-1 expression is critical to …