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Articles 1 - 30 of 63
Full-Text Articles in Medicine and Health Sciences
The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos
The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos
All ETDs from UAB
Cerebral malaria (CM) is one of the most severe clinical complications of P. falciparum malaria with a fatality rate of 15-30%, and 10% of CM survivors have permanent neurological sequelae. Since inflammation is a central pathophysiological tenet of CM, we began examining the role of the complement system in pathogenesis of experimental cerebral malaria (ECM) using Plasmodium berghei ANKA (PbA) model. Previous studies using this model indicated that mice naturally deficient in complement component C5 were protected from cerebral complications, and wild type mice treated with anti-C5aR antibody were also protected. To determine the protective mechanism of naturally-C5 deficient mice, …
Rhodopsin Trafficking And Retinal Function, Nicholas Joseph Reish
Rhodopsin Trafficking And Retinal Function, Nicholas Joseph Reish
All ETDs from UAB
The health and maintenance of rod photoreceptors depends on the high-fidelity vectorial transport of rhodopsin from its site of synthesis in the inner segment to its final resting place in the outer segment disks. Multiple molecular interactions play a role in this process, including the interaction of the small GTPase rab11a with rhodopsin that was first described in vertebrates in amphibians. We found that the interaction of the small GTPase rab11a and rhodopsin is conserved in mammalian retina. This interaction is direct, is abrogated by human disease-causing truncation mutations in rhodopsin, and does not depend on the nucleotide binding status …
Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo
Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo
All ETDs from UAB
CD4 T cells are central to the organization of the immune response through the secretion of cytokines that recruit and activate other immune cells. Following infection and pathogen control, the majority of the effector CD4 T cells undergo apoptosis, leaving a subset that persists and gives rise to the memory T cell pool. Upon encountering the same pathogen, memory CD4 T cells respond rapidly, providing enhanced protection from re-infection. What determines which effector CD4 T cells will survive is unclear; however, there are a number of factors both intrinsic to the cell as well as external signals from the environment …
Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey
Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey
All ETDs from UAB
The dentate gyrus (DG) contains neural stem cells that continually generate new neurons throughout life. The contribution of adult neurogenesis to hippocampal function is not well understood, but ablation or silencing of adult-generated neurons in the DG disrupts learning and memory, and neurogenesis is altered in many pathologies associated with impaired cognition including Alzheimer's Disease, epilepsy, and schizophrenia. Neurogenesis in the DG is a stepwise process in which neural stem cells leave the cell cycle and undergo an approximately two month long maturation process to form fully functional dentate granule cells (GCs) that are indistinguishable from those formed during development. …
The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore
The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore
All ETDs from UAB
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …
Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li
Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li
All ETDs from UAB
Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …
The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu
The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu
All ETDs from UAB
Insulin resistance plays a central role in the pathogenesis of Type 2 Diabetes (T2DM) and involves diminished stimulation of glucose transport in skeletal muscle. Improvements in insulin sensitivity are essential for both prevention and treatment of T2DM. However, the limitation of current medications highlights the need for alternative molecular regulators of insulin action and developing new insulin sensitizers. Our laboratory has initially identified roles for the orphan nuclear receptor NR4A3 in insulin-sensitization and stimulation of glucose transport. However, the cellular effect and downstream mechanisms of NR4A3 and its agonists (e.g. 6-mercaptopurine/6-MP) on insulin effector system in skeletal muscle remain unknown. …
Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James
Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James
All ETDs from UAB
Human Immunodeficiency Virus (HIV) is one of the leading infectious diseases in the world. In spite of substantial progress in the advancement of antiretroviral therapy for HIV treatment, new infections outpace the number of infected persons initiating ART. Therefore, the prevention of HIV remains a crucial health issue. Pre-Exposure Prophylaxis, (PrEP), which involves using one or more antiretroviral agents to reduce the risk of HIV infection prior to potential exposure, has shown effectiveness at reducing HIV transmission in study volunteers with different sexual orientation around the world. The clinical pharmacology of antiretroviral drugs, specifically tenofovir (TFV) and emtricitabine (FTC), in …
The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure
The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure
All ETDs from UAB
Post-translational modifications (PTMs) are important contributors to protein bio-genesis and function. CFTR in particular is known to be regulated by multiple PTMs, in-cluding glycosylation, phosphorylation, and ubiquitination. The functional significance and specific CFTR residues responsible for the majority of PTMs within CFTR are not known. The goal of this dissertation was to identify and characterize novel PTMs that influence wild-type and F508del CFTR. The study employed a combination of tandem and multiple reaction ion monitoring mass spectrometry to identify covalent side chain attachments. Analysis revealed the specific locations of numerous phosphorylated resi-dues, several sites of methylation, and more than twenty-five …
Phenotypic Analysis Of B Cells In Hla*B44 Positive Patients That Exhibit Common Variable Immunodeficiency And Recurrent Sino-Pulmonary Infections, Eva Szymanska Mroczek
Phenotypic Analysis Of B Cells In Hla*B44 Positive Patients That Exhibit Common Variable Immunodeficiency And Recurrent Sino-Pulmonary Infections, Eva Szymanska Mroczek
All ETDs from UAB
Depressed serum immunoglobulin levels and recurrent sinopulmonary infections mark Common Variable Immune Deficiency (CVID). Many family members of CVID patients also suffer Recurrent Sino-Pulmonary Infection (RESPI) but have normal serum immunoglobulins. We identified HLAB44 positive identical female twins who suffer sinopulmonary infections and are discordant for CVID and RESPI. Flow cytometry subsets showed equivalent numbers of immature B cells (BC) in both twins, but lower numbers of transitional and mature BC in the CVID twin. Presented is an in-depth comparison of V (D) J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between µ H chain repertoires …
The Impact Of Transcription And Nucleoid-Associated Proteins On Dna Supercoiling In Escherichia Coli And Salmonella Typhimurium, Andrews Agbleke
The Impact Of Transcription And Nucleoid-Associated Proteins On Dna Supercoiling In Escherichia Coli And Salmonella Typhimurium, Andrews Agbleke
All ETDs from UAB
Bacterial chromosomes are maintained under constant negative supercoiled stress that influences almost all cellular processes including DNA replication, transcription, segregation, site-specific and homologous recombination, and other DNA transposition. The average supercoiling density of the chromosome is generated by gyrase, and supercoil equilibrium is maintained by two other topoisomerases topo I and topo IV. The supercoils generated by gyrase can diffuse over 10 kb domains. The other half of the chromosome's supercoil structure is connected to abundant nucleoid-associated proteins (NAPs). My goal was to characterize factors other than gyrase that participate in generating or regulating supercoil dynamics in Escherichia coli and …
Studies Of Dna Gyrase Activity In Escherichia Coli And Salmonella Enterica Serovar Typhimurium., Nikolay Sergeyevich Rovinskiy
Studies Of Dna Gyrase Activity In Escherichia Coli And Salmonella Enterica Serovar Typhimurium., Nikolay Sergeyevich Rovinskiy
All ETDs from UAB
Gyrase introduces negative supercoils into bacterial DNA. In balance with topoisomerase I, it contributes to the maintenance of constant negative DNA supercoiling. It was shown that in Escherichia coli negative supercoil density of pBR322 plasmid is higher than in Salmonella typhimurium. One of the possible explanations of this phenomenon is a difference of DNA gyrase activity between E. coli and S. typhimurium. We developed in vitro assay of gyrase activity which has shown that DNA gyrases of E. coli and S. typhimurium have the same supercoiling end point, but E. coli gyrase works slightly faster than the S. typhimurium enzyme. …
Role Of Gsk3 In The Immunopathogenesis Of Eae, Amber Rowse
Role Of Gsk3 In The Immunopathogenesis Of Eae, Amber Rowse
All ETDs from UAB
Lithium, a glycogen synthase kinase 3 (GSK3) inhibitor, ameliorates experimental autoimmune encephalomyelitis (EAE), the murine model of multiple sclerosis (MS) in different mouse models. However, the mechanism of lithium's attenuation of EAE and the role of GSK3 in these processes are currently unknown. IFN-g producing Th1 cells and IL-17-producing Th17 cells are both effector cells in MS and in EAE models. However, relapsing remitting MS patients segregate into Th1 or Th17 serum cytokine signatures and each is differentially responsive to IFN-ß therapy, a first line therapy for MS. Studies in this dissertation revealed a differential effect of lithium on Th1 …
The Role Of Gadd45b In Hippocampus-Dependent Cognition, Synaptic Plasticity And Activity-Associated Transcriptional Dynamics, Faraz Sultan
The Role Of Gadd45b In Hippocampus-Dependent Cognition, Synaptic Plasticity And Activity-Associated Transcriptional Dynamics, Faraz Sultan
All ETDs from UAB
An expanding body of literature argues for a pivotal role of molecular epigenetic mechanisms in memory. Defined as mechanisms that regulate gene expression in the absence of DNA sequence modifications, these regulate various stages of memory-associated transcription. These phenomena are present at diverse anatomical subregions of the central nervous system (CNS) and regulate corresponding behaviors. Epigenetic mechanisms comprise a unique category of behavioral and physiological modulators because of their potential to modify the cellular phenotype in a stable manner. Hence, epigenetics offers a novel potential solution to a central paradox in memory retention: the finding that most putative molecular substrates …
Regulation Of Capsule By Cpsa And Global Regulatory Networks In Streptococcus Pneumoniae Type 2, Kanupriya Gupta
Regulation Of Capsule By Cpsa And Global Regulatory Networks In Streptococcus Pneumoniae Type 2, Kanupriya Gupta
All ETDs from UAB
Streptococcus pneumoniae is a major human pathogen that can reside asymptomatically in the nasopharynx before causing invasive disease by entering systemic sites. This involves regulation of colonization and virulence factors including capsule. cps2A, the first gene of the capsule (cps) locus has been proposed to regulate capsule, however its exact role and mechanism is not well understood. A complete deletion of cps2A resulted in enhanced capsule levels, with no alteration in the transcription levels of cps genes. Complementation of Cps2A restored wild type levels of capsule. Expression of the C-terminal tail alone was able to partially complement the deletion strain, …
Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che
All ETDs from UAB
Dengue virus (DENV) has become a huge public health concern around the world with no vaccine or antivirals available. More than one-third of the world's population is living in areas at risk of infection. To conquer the dengue disease, a better understanding of virus-host interactions and development of the appropriate therapeutic treatments are required. In this dissertation, we first broadly reviewed the factors involved in dengue viral entry and the role of tight junctions as a pathogen target. Second, we developed, optimized and validated a high throughput screening (HTS) assay for anti-dengue virus drug screening. Taking advantage of using live …
Structure-Function Analysis Of Tyrosyl-Dna Phosphodiesterase I, Evan Comeaux
Structure-Function Analysis Of Tyrosyl-Dna Phosphodiesterase I, Evan Comeaux
All ETDs from UAB
Tyrosyl-DNA phosphodiesterase I (Tdp1) functions to remove 3'phospho-DNA adducts, such as eukaryotic DNA Topoisomerase I (Top1) covalently bound to the DNA by a 3'phospho-tyrosyl bond. As member of the Phospholipase D superfamily Tdp1 contains two HxK(n)N motifs, each of which provide a catalytic histidine: one functioning as a nucleophile to bind the 3'phosphate and the other as a general acid/base to hydrolyze Tdp1's 3'phospho-histidyl bond. Mutation of the general acid/base catalytic histidine (Hisgab) to arginine has been implicated in the autosomal recessive neurodegenerative disease SCAN1. Further study of the yeast enzyme revealed that substitution of Hisgab in yeast Tdp1 to …
Tgf-Ss And Erg In Intervertebral Disc Development, Megan Karen Cox
Tgf-Ss And Erg In Intervertebral Disc Development, Megan Karen Cox
All ETDs from UAB
The intervertebral disc (IVD) is a fibrocartilaginous tissue that acts as a shock absorber between adjacent vertebrae in the spinal column. It is comprised of two parts, the inner jelly-like nucleus pulposus (NP) and the outer more fibrous annulus fibrosus (AF). Most IVD research has focused on the development of the NP, which is derived from condensations of the notochord involving sonic hedgehog (Shh) signaling. In contrast, very little is known about the molecular mechanisms underlying the specific development of the AF of the IVD. The AF is derived from the sclerotome, which is formed by the ventral half of …
Adapter Based Strategies For Adenovirus Vector Retargeting To T Lymphocytes, Matthew S. Beatty
Adapter Based Strategies For Adenovirus Vector Retargeting To T Lymphocytes, Matthew S. Beatty
All ETDs from UAB
Adenoviruses are the most commonly used gene therapy vector for cancer therapy clinical trials. While adenovirus has shown a great track record in a variety of cancer therapeutics it has not progressed as a vector system for the modification of T lymphocytes. One of the major roadblocks towards utilizing adenovirus for T cell therapy is the lack of coxsackie virus and adenovirus receptor on the cell surface of T cell lineages. Exploitation of alternative receptors has allowed adenovirus vectors to be utilized in a variety of cell types that native adenovirus type 5 cannot infect. Thus, retargeting adenovirus to an …
Hur Regulation In Central Nervous System Disorders, Crystal G. Wheeler
Hur Regulation In Central Nervous System Disorders, Crystal G. Wheeler
All ETDs from UAB
In inflammatory diseases of the central nervous system (CNS), astrocytes play a major role in the systemic response to disease by either enhancing or limiting the inflammatory response through secretion of growth factors or cytokines. HuR RNA binding protein regulates many genes involved in inflammation. Inflammatory diseases such as brain tumors, Amylotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), have been linked to HuR, by our laboratory and others. To determine whether astrocytic overexpression of HuR would regulate inflammation in diseases of the CNS, we designed a transgenic mouse in which the HuR gene is overexpressed. In the first study, …
Intrinsic Properties Of Rna Polymerase I And Trans-Acting Factors Control Transcription Elongation Efficiency, Olga V. Viktorovskaya
Intrinsic Properties Of Rna Polymerase I And Trans-Acting Factors Control Transcription Elongation Efficiency, Olga V. Viktorovskaya
All ETDs from UAB
Transcription of ribosomal (r) DNA by RNA polymerase I (Pol I) is the initial step of ribosome synthesis. Pol I transcription is unique in its high rate of initiation, specific organization within the nucleolus and tight connection to cell growth and proliferation. Moreover, transcription elongation by Pol I is functionally coupled with rRNA processing and assembly of the ribosomes. Regulatory insights into transcription elongation by Pol I and its interface with rRNA processing are limited, despite decades of research. To fulfill that gap, we asked several important questions: Do the obvious functional divergences between Pol I and other eukaryotic polymerases …
The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker
The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker
All ETDs from UAB
pcpA is under control of the Mn 2-dependent repressor PsaR. In the high manganese environment of mucosal sites pcpA gene expression is repressed and at the low manganese environment of the lung and blood derepression of pcpA gene expressionis observed. Previous data has shown that immunization of mice with rPcpA elicits protection against pneumonia and sepsis but had no effect on nasal colonization. We and others have shown that pcpA expression significantly enhances adherence of pneumococci to lung epithelial cell lines and although it is a virulence factor for pneumonia in mice there is no biologically relevant role for PcpA …
Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar
Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar
All ETDs from UAB
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …
Glioma-Vasculature Interactions, Stacey Watkins
Glioma-Vasculature Interactions, Stacey Watkins
All ETDs from UAB
Malignant gliomas are highly invasive brain tumors, which lack effective treatment options. To date, the standard therapy includes surgical debulking followed by chemotherapy and radiation. Despite efforts to eradicate the disease, the median patient survival time is only 14 months. In an attempt to discover novel therapies, research has focused on understanding the heterogeneous biological mechanisms employed by these cells. Uniquely, they do not metastasize through the vasculature or lymphatics like other solid cancers but alternatively, glioma cells utilize the abluminal surface of the vasculature to guide invasion and migration throughout the brain. The intimate association between glioma cells and …
Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo
Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo
All ETDs from UAB
Mutations in the AP3-ß1 gene are known to cause Hermansky-Pudlak syndrome type 2 (HPS2) in humans and canine cyclic hematopoiesis (CH) in gray collie dogs. HPS2 patients have severe congenital neutropenia (SCN), and dogs have cyclic neutropenia (CN). The mechanism behind neutropenia is uncertain. Pearl mice have an AP3-ß1 mutation, but whether they actually have neutropenia has not yet been evaluated. This dissertation presents a discussion of the evaluation of neutropenia in pearl mice, hematopoietic progenitor cell mobilization defect in pearl mice and finally an evaluation of methods of dog-to-mouse xenotransplantation to establish a xenotransplant model of the dog hematopoietic …
Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah
Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah
All ETDs from UAB
Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …
Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner
Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner
All ETDs from UAB
A limited amount of migration occurs in the adult brain, including migration of neuroblasts during adult neurogenesis and pathological migration of primary brain tumors. Ion channels are commonly utilized during migration to allow shape and volume changes required for cell movement, and we specifically examine the role of KCa3.1 in the adult brain. These channels are well-suited to facilitate movement because they respond to common migration signals, i.e. intracellular Ca2+ changes, and efflux K+, allowing the outflow of water and cell volume regulation. Our findings suggest that KCa3.1 is highly expressed in migratory cells, adult neuroblasts and glioma cells, but …
Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton
Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton
All ETDs from UAB
Aspergillus fumigatus is a ubiquitous saprophytic fungus which can potentially cause life-threatening infections in immunocompromised individuals. Although a serious threat, current treatments are largely ineffective at reducing morbidity and mortality. To this end, we have characterized a monoclonal antibody generated against Group B Streptococci, type Ib, which also recognizes Aspergillus fumigatus conidia and hyphae. We show that this antibody appears to bind a similar epitope on both pathogens and provides a significant degree of protection in a murine model of invasive aspergillosis via a mechanism that appears to be dependent on complement. The studies we performed using this antibody should …
Virus-Induced Inflammation And Central Nervous System Development, Kate Kosmac
Virus-Induced Inflammation And Central Nervous System Development, Kate Kosmac
All ETDs from UAB
Congenital human cytomegalovirus (HCMV) infection is a complex cause of central nervous system (CNS) disease. Infection with HCMV during pregnancy results in virus transmission across the placenta and infection of the fetus. With a seroconversion rate in pregnant women between 1% and 4%, HCMV is the most frequently transmitted virus from mother to developing child. Each year between 2,000 and 4,000 infants will suffer from long-term neurologic deficits as a result of congenital infection. The well documented CNS sequelae resulting from congenital HCMV infection have described a wide range of damage without a specific set of pathologic markers for disease. …
Epigenetic Markers In The Developing Postnatal Brain, Rebecca Kaye Simmons
Epigenetic Markers In The Developing Postnatal Brain, Rebecca Kaye Simmons
All ETDs from UAB
Epigenetic mechanisms provide a critical and plausible mechanism by which genes and the environment can interact and have been implicated in a number of diseases and disorders. In order to better understand how epigenetic mechanisms go awry in a diseased brain we must first understand how epigenetic mechanisms unfold during normal development. The present body of work begins to examine the role of DNA methylation in normal development and how it may contribute to a rodent model of emotion dysfunction. Using a variety of techniques, we evaluated the transcript, protein and functional output levels of DNA methyltransferase1, -3a, and -3b …