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G Protein-Coupled Inwardly-Rectifying Potassium (Girk) Chanels Mediate Entrainment Of Circadian Rhythms, Lauren Marie Hablitz Jan 2015

G Protein-Coupled Inwardly-Rectifying Potassium (Girk) Chanels Mediate Entrainment Of Circadian Rhythms, Lauren Marie Hablitz

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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, …


Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson Jan 2015

Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson

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The secondary mouth and its associated face and jaws were an important evolutionary adaptation in the vertebrate lineage. The secondary mouth is formed from facial prominences including the fronto-nasal prominence and the 1st pharyngeal-arch derived maxillary and mandibular prominence. Cranial neural crest cells within these prominences give rise to the connective tissues of face and jaws, and strict spatio-temporal regulation of cranial neural crest cell fate patterning and subsequent prominence outgrowth is vital to normal facial development. Oral-facial clefting (OFC) is a common morbid human birth disorder characterized by disrupted oral and craniofacial morphogenesis. Our previous studies demonstrate that a …


Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski Jan 2015

Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski

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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 …


The Role Of Ribosome Biogenesis In Exercise-Induced Skeletal Muscle Anabolism In Aging, Michael Stec Jan 2015

The Role Of Ribosome Biogenesis In Exercise-Induced Skeletal Muscle Anabolism In Aging, Michael Stec

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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 …


Characterizing The Nuclear Import And Functions Of Cystin, The Ciliary Protein Disrupted In The Cpk Mouse Model Of Recessive Polycystic Kidney Disease, Jacob Asher Watts Jan 2015

Characterizing The Nuclear Import And Functions Of Cystin, The Ciliary Protein Disrupted In The Cpk Mouse Model Of Recessive Polycystic Kidney Disease, Jacob Asher Watts

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Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a ma-jor cause of pediatric morbidity and mortality. Typically, orthologous animal models are the mainstay for pathogenic studies of human diseases. However, gene-targeting of Pkhd1, the mouse ortholog of the ARPKD gene, results in mutants with little or no kidney disease. In contrast, disruption of the non-orthologous gene, Cys1, in the cpk mouse model closely phenocopies human ARPKD. We speculate that this phenotypic similarity suggests that the Pkhd1 and Cys1 genes encode proteins (FPC and cystin, respectively) that share, at least in part, common molecular pathways. Our laboratory, as well as …


C-Reactive Protein, Autoimmunity, And Inflammation In The Central Nervous System, Tyler T. Wright Jan 2015

C-Reactive Protein, Autoimmunity, And Inflammation In The Central Nervous System, Tyler T. Wright

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C-reactive protein (CRP) is an acute phase reactant whose blood concentration rises in response all types of inflammation. And while CRP is widely used as a clinical marker of inflammation, it has several biological functions, e.g. activation of the classical complement cascade and binding Fcγ receptors in order to mediate multiple immune processes. The full extent of CRP’s physiological activities has not yet been fully elucidated, but there is significant evidence to establish that CRP plays an important role in the onset and progression of autoimmune disease. Seminal work from our lab showed that human CRP, hepatically expressed in transgenic …


Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue Jan 2015

Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue

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A nonsense mutation introduces a premature terminations codon (PTC) into an open reading frame (ORF) upstream of a normal stop codon and results in truncated protein production. In frame PTCs account for ~11% of all mutations that cause human genetic diseases. To treat PTC-associated disorders, one approach is to use drugs that facilitate the insertion of amino acids carried by near-cognate aminoacyl-tRNAs at PTCs. Aminoglycosides were shown to suppress nonsense mutations and restore full-length protein production. This process is also termed as readthrough. However, their low efficiency and their potential to induce ototoxicity and nephrotoxicity limits their long-term application for …


Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows Jan 2015

Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows

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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 …


Gaba(A) Receptor Trafficking And Localization In Schizophrenia, Toni Marie Mueller Jan 2015

Gaba(A) Receptor Trafficking And Localization In Schizophrenia, Toni Marie Mueller

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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 Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki Jan 2015

The Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki

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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 Jan 2015

Role Of Macrophages In The Cardiomyopathy Associated With Obesity And Type 2 Diabetes, Mehak Goel

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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 …


Competition From New Neurons Drives Circuit Refinement In The Adult Dentate Gyrus, Elena W. Adlaf Jan 2015

Competition From New Neurons Drives Circuit Refinement In The Adult Dentate Gyrus, Elena W. Adlaf

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The hippocampus encodes sensory information into memories. The dentate gyrus (DG) region is viewed as the entry point into the hippocampus, receiving sensory and spatial signals from perforant path axons of the entorhinal cortex (EC). Ever since researchers discovered a neurogenic niche in the subgranular zone (SGZ) of the DG in adult animals and humans, many studies have been aimed at discovering how these continually proliferating granule cells (GCs) contribute to the network. Immature GCs have dendrites that project densely into the molecular layer alongside mature GCs and there is morphological evidence that immature excitatory spines preferentially synapse onto existing …


Robust Production Of Mature Ribosomal Rna Is Directly Influenced By Multiple Steps Within The Transcription Cycle, Krysta Engel Jan 2015

Robust Production Of Mature Ribosomal Rna Is Directly Influenced By Multiple Steps Within The Transcription Cycle, Krysta Engel

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Cellular growth depends on the capacity for protein synthesis, and likewise ribosome biogenesis. Therefore, robust rRNA synthesis by RNA Polymerase I (Pol I) is a critical component of cell growth. The work reported in this dissertation highlights the contribution of polymerase domains and trans-acting proteins during rRNA synthesis and ribosome biogenesis. Eukaryotes utilize three homologous nuclear RNA polymerases (RNAPs) to express their genomes. The trigger loop (TL) is a well conserved region within the active site of multi-subunit RNAPs that plays a direct role during the nucleotide addition cycle. Analysis of Pol II TL mutants has suggested that catalysis is …


The Effect Of Thioredoxin-Interacting Protein Induced Microrna-200 Family Members On Pancreatic Beta Cells, Stephen Filios Jan 2015

The Effect Of Thioredoxin-Interacting Protein Induced Microrna-200 Family Members On Pancreatic Beta Cells, Stephen Filios

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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. …


Transient-State Kinetic Analysis Of The Rna Polymerase I Nucleotide Incorporation Mechanism, Francis Dean Appling Jan 2015

Transient-State Kinetic Analysis Of The Rna Polymerase I Nucleotide Incorporation Mechanism, Francis Dean Appling

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The diversity of enzymes and the reactions which they catalyze is enormous. Careful study of enzymatic reaction mechanisms has taught us a great deal about chemical reactivity and has given us insight into the chemical and physical basis of life. One particularly ubiquitous class of enzymes, the RNA polymerases, are expressed in all forms of life. RNA polymerases are central components of nucleic acid metabolism and display a variety of distinctive enzymatic features; two points which solicit their thorough study. The central theme of this dissertation is the use of kinetic techniques to describe enzymatic reaction mechanisms. Although the main …


Protumorigenic Role Of Cathelicidin-Related Antimicrobial Peptide In Chemotaxis And Differentiation Of Myeloid Lineage During Prostate Cancer Progression, Ha-Ram Cha Jan 2015

Protumorigenic Role Of Cathelicidin-Related Antimicrobial Peptide In Chemotaxis And Differentiation Of Myeloid Lineage During Prostate Cancer Progression, Ha-Ram Cha

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A growing body of evidence indicates a positive correlation between the expression of human antimicrobial peptide leucine leucine 37 (LL-37) and the progression of epithelial cancers, including carcinomas of the breast, lung, ovary, and prostate. Although the molecular mechanisms for this correlation have not yet been clearly elucidated, the primary function of LL-37 as a chemotactic molecule for innate immune effector cells suggests its possible association in coordinating protumorigenic mechanisms mediated by tumor-infiltrating immune cells. Using a mouse model of epithelial prostate cancer (PCa), the present study identified a unique role for cathelicidin-related antimicrobial peptide (CRAMP), a murine orthologue of …


Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson Jan 2015

Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson

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Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are all characterized by metabolic dysfunction, increased oxidative damage to proteins and organelles, formation of proteinaceous inclusions, decreased autophagic and proteasomal function, and eventual neuronal and glial cell death. While our understanding of the mechanisms that underlie many of these pathologies is constantly growing, their exact cause, onset, interplay and progression still remain unclear. The gap between the description of disease pathologies and understanding the fundamental mechanisms of disease pathogenesis, progression and potential therapeutics to mitigate disease progression is still large. Based on the observation that altered glucose utilization, …


Stat4 Regulates Multiple Pathogenic Mechanisms Of Cd4 T Cells In Experimental Autoimmune Encephalomyelitis, A Model Of Multiple Sclerosis, Ian Lee Mcwilliams Jan 2015

Stat4 Regulates Multiple Pathogenic Mechanisms Of Cd4 T Cells In Experimental Autoimmune Encephalomyelitis, A Model Of Multiple Sclerosis, Ian Lee Mcwilliams

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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). …


Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley Jan 2015

Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley

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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 …


A Novel Role For Usp14 In Regulating Non-Proteolytic Ubiquitin Signaling, Jada Hallengren Vaden Jan 2015

A Novel Role For Usp14 In Regulating Non-Proteolytic Ubiquitin Signaling, Jada Hallengren Vaden

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Loss of the deubiquitinating enzyme (DUB) USP14 in the ataxia (axJ) mice leads to altered neuromuscular junction (NMJ) structure, reduced synaptic transmission at the NMJ, and decreased mobility. However, the types of processes that USP14 regulates in the nervous system remain unclear. Because association with the proteasome stimulates USP14's ubiquitin hydrolase activity, it is thought to act primarily on proteasomal substrates. Therefore, one way for USP14 to support nervous system function is by modulating protein turnover. While a number of studies done in yeast and immortalized cell lines demonstrate that loss or inhibition of USP14 alters proteasome function, there is …


Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard Jan 2015

Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard

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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 …


Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi Jan 2015

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

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The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …


Bcla As An Adjunct To Current Bacillus Anthracis Vaccination And Therapy Protocols, Juan Bosco Rodriguez Barrantes Jan 2015

Bcla As An Adjunct To Current Bacillus Anthracis Vaccination And Therapy Protocols, Juan Bosco Rodriguez Barrantes

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Bacillus anthracis (Ba) is a Gram,-positive zoonotic bacterium that causes inhala- tional, cutaneous and intestinal Anthrax Disease. Although the infectious form of Ba is its endospore (spore), only the tripartite toxin-producing vegetative bacteria causes disease pathology. While current vaccination strategies target the Protective Antigen (PA) com- ponent of this toxin, vaccine-elicited immunity to the spore form of Ba is lacking. How- ever, vaccines targeting spore components of Ba have the potential to neutralize the in- fectious form of Ba. We sought to determine if antibodies elicited through immunization with the main antigenic component of the spore surface- Bacillus collagen-like protein …


Investigating The Role Of Myristoylated Alanine Rich C Kinase Substrate's (Marcks's) Effector Domain In Lung And Brain Cancer Biology, Timothy D. Rohrbach Jan 2015

Investigating The Role Of Myristoylated Alanine Rich C Kinase Substrate's (Marcks's) Effector Domain In Lung And Brain Cancer Biology, Timothy D. Rohrbach

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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 …


Innate Immunity Mechanisms In Parkinson Disease, Mark Moehle Jan 2015

Innate Immunity Mechanisms In Parkinson Disease, Mark Moehle

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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 Jan 2015

Structural Implications Of P22 Bacteriophage Coat Protein A-Domain Modifications, David Samuel Morris

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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 …


Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward Jan 2015

Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward

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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 Jan 2015

Caenorhabditis Elegans Sperm Chemotaxis, Hieu Dinh Hoang

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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 …


The Mspa Nanopore As A Sensor For Dna Sequencing, Mikhail Pavlenok Jan 2015

The Mspa Nanopore As A Sensor For Dna Sequencing, Mikhail Pavlenok

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Nanopore sequencing is a novel and promising DNA sequencing method. This single molecule technique is capable of long reads, retains epigenetic information, and is inexpensive and fast. In this method ionic current is measured while single-stranded DNA is electrophoretically translocated through a nanometer-scale pore. Each passing nucleotide blocks current with characteristic amplitude and duration which are used to identify DNA sequence. MspA is the primary porin of M. smegmatis and mediates the diffusion of small, hydrophilic nutrients across the outer membrane. MspA is an octameric, channel-forming protein and represents the founding member of a new class of mycobacterial outer membrane …


The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues Jan 2015

The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues

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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. …