Digital Commons Network^™

Modulation Of Intrinsic Activity In Sensory Cortex Facilitates Task Performance, Aburahman Elkhetali

All ETDs from UAB

Due to the changing demands of the environment and our behavioral intentions the brain has to adapt in order to produce task appropriate responses. Part of the challenge is the large amount of sensory information received by the brain. Depending on individu-al goals, the brain must select and react to task appropriate stimuli while ignoring other irrelevant sensory input. Since behavioral intentions are dynamic, this requires the re-sponses within the brain to also be dynamic. Cognitive control, exerted by higher centers on sensory cortex allow for selection of task relevant stimuli. In this study we find that intrinsic, non-stimulus driven …

Adap1 And Arf6 Mediate Regulated Secretory Trafficing In Neurosecretory Cells And Neurons, Sharday Ewell

All ETDs from UAB

ADP ribosylation factor 6 (Arf6) is a member of the Arf family of small GTPases known to function in vesicular membrane trafficking and cytoskeletal organization. Arf6 cycles between its GTP and GDP bound states, facilitated by GTP exchange factors (GEFs) and GTPase activating proteins (GAPs), respectively. In my dissertation studies I have investigated the neuronal functions of Arf6 and ADAP1, an Arf6 GAP and candidate PI 3-kinase target required for dendritic differentiation in developing neurons. I demonstrated that in neurosecretory PC12 cells and neurons, ADAP1 and Arf6 colocalize with regulated secretory granules (SGs) that traffic chromogranin B and brain-derived neurotrophic …

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 …

The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor

All ETDs from UAB

O-GlcNAcylation is a dynamic protein posttranslational modification that adds the monosaccharide ß-N-acetylglucosamine (GlcNAc) to specific serine and threonine residues on nucleocytoplasmic proteins. The hippocampus is a part of brain that has been shown to play a crucial role in learning and memory. Hippocampal neurons have high expression of O-GlcNAc transferase and O-GlcNAcase, which catalyze the addition and removal of GlcNAc from proteins respectively. Moreover, synaptic plasticity which is the strengthening or weakening of synaptic function on short- and long-term time scales is believed to be a cellular correlate of learning and memory. Several forms of synaptic plasticity have been characterized …

An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas

All ETDs from UAB

Acute inflammation is a necessary component for the clearance of pathogens. Cells at the site of infection utilize highly conserved receptors to both recognize microbes and induce the production of pro-inflammatory stimuli. These stimuli set off a chain reaction that includes localized vasodilation, leukocyte infiltration, and tissue destruction, collectively known as inflammation. Tightly controlled, this process is protective, and can compartmentalize the damage to a defined area, but when dysregulated can be catastrophic, inducing chronic inflammation and even death. Families of innate receptors can modulate inflammatory processes, and in doing so, increase or decrease their severity, as well as tailor …

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 …

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 …

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

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 …

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 …

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, …

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 …

Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston

All ETDs from UAB

Malignant gliomas are the most frequently diagnosed and the most fatal primary brain tumors. Innovative therapeutic approaches are necessary to combat these devastating cancers, and oncolytic herpes simplex virus type-1 (oHSV) deleted of the γ134.5 neurovirulence gene is a promising adjunctive therapy. The primary mechanism of tumor clearance by oHSV is lytic replication specifically within malignant cells. oHSV also stimulates tumor infiltration of cytotoxic immune effector cells that can participate in tumor clearance. However, cytotoxic immune cells target oHSV as well as tumor, which may limit therapeutic efficacy. Further knowledge regarding the nature of these interactions and how the interactions …

The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer

All ETDs from UAB

PCV13 is the current pneumococcal protein conjugated vaccine made up of the 13 most clinically relevant capsular polysaccharides. While protective, it is limited to a small portion of the overall serotypes of Streptococcus pneumoniae. The possibility of "serotype replacement" by serotypes not covered by the vaccine and the high cost of producing this conjugated polysaccharide vaccine stress the need for a protein based vaccine, one that is more broad in its protection. Pneumococcal surface protein A (PspA) has been shown to be both immunogenic and protective in mice and is a promising protein vaccine candidate. However, there are no current …

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, …

Role Of Endothelial Mannose Residues In Monocyte Adhesion Under Flow, David Wayne Scott

All ETDs from UAB

Atherosclerosis is a chronic inflammatory disease of the vessel wall and underlying cause of most cardiovascular disease. Much is understood about the nature of atherosclerosis development, including contributions from leukocytes that drive the disease process forward. The general process by which leukocytes are trafficked to sites of atherosclerosis development, and sites of inflammation in general, is understood and relies upon endothelial expressed protein adhesion molecules which serve as ligands for cognate leukocyte receptors. While these adhesion molecules share the post-translation modification of N-glycosylation, relatively little is known as to what functional role these modification plays in: i) interactions of leukocytes …

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 …

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 …

The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales

Open Access Theses & Dissertations

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to …

Using The Theory Of Planned Behavior As A Predictor Of Radiologic Technologists' Use Of Patient Radiation Protection Best Practices: A Regional Study, Brenda L. Boyd

Dissertations

Problem. A growing concern exists that patients are receiving an increase in radiation exposure while undergoing medical imaging exams. According to a March 2009 report by the National Council on Radiation Protection and Measurements (NCRP), the U.S. population's total exposure to ionizing radiation has nearly doubled over the past two decades. With the introduction of new digital radiology equipment, patient dose is on the rise. Possible reasons for a radiologic technologist's behavior include: influence by availability or lack of equipment, policies, social pressure, attitudes, and a safety culture. Little research has been done in this area, specifically with applying a …

The Mesocorticolimbic Dopamine Pathway Reconstituted In Vitro: Glutamate Receptors And Corticosteroid-Methamphetamine Neurotoxicity, Jennifer N. Berry

Theses and Dissertations--Psychology

Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the …

Influence Of Pramipexole On Probability Discounting And Ventral Pallidal Function: Assessments In Parkinsonian-Like Rats, Sandra Lynn Rokosik-Kletzel

Dissertations

People with neuropathologies who are treated with dopamine agonists may be at risk to develop impulse control disorders. The overall goal of this dissertation project was to expand our knowledge on the neuropsychopharmacology of dopamine agonist-induced impulsivity. At the time this dissertation was being developed, pramipexole was the drug, gambling was the behavior, and Parkinson's disease (PD) was the pathology most widely reported for this phenomenon. Therefore, we first developed a behavioral paradigm (i.e., probability discounting) to measure risk-taking, one aspect of gambling. Utilizing this paradigm, we determine if risk-taking was altered after acute and/or chronic pramipexole treatment. We incorporated …

Alpha-Synuclein Aggregates Activate The Nlrp3 Inflammasome Following Vesicle Rupture, Rudy Orlando Cedillos

Master's Theses

Parkinson's disease (PD) and related synucleinopathies are progressive neurodegenerative disorders that feature the accumulation of intracellular inclusions known as Lewy bodies (LBs) in the brain. The presynaptic protein α-synuclein is the primary constituent of LBs and has been documented to play a major role in the pathogenesis of synucleinopathies. Recently, aggregated α-synuclein has been implicated in prompting microglia-mediated inflammation, a process associated with the progression of neuronal death in neurodegenerative disorders. Although the mechanisms surrounding the induction of neuroinflammation are not well understood, the recently discovered inflammasome-forming NLR proteins have emerged as regulators of inflammation. In this study, we sought …

P900: A Putative Novel Erp Component That Indexes Counter-Measure Use In The P300-Based Concealed Information Test, John B. Meixner Jr., Elena Labkovsky, J. Peter Rosenfeld, Michael R. Winograd, Michael Winograd, Alexander Sokolovsky, Jeff Weishaar, Tim Ullmann

Scholarly Works

Countermeasures pose a serious threat to the effectiveness of the Concealed Information Test (CIT). In a CIT experiment, Rosenfeld and Labkovsky in Psychophysiology 47(6):1002–1010, (2010) observed a previously unknown positive ERP component at about 900 ms poststimulus at Fz and Cz that could potentially serve as an index of countermeasure use. Here, we explored the hypothesis that this component, termed P900, occurs in response to a signal that no further specific response is required in a trial, and could thus appear in countermeasure users that respond differentially depending on the stimulus that appears. In the present experiments, subjects viewed four …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Histology And Ultrastructure Of Transitional Changes In Skin Morphology In The Juvenile And Adult Four-Striped Mouse (Rhabdomys Pumilio), Eranée Stewart, Moyosore Salihu Ajao, Amadi O. Ihunwo

Brain and Mind Institute

The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the …

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Intronic Non-Cg Dna Hydroxymethylation And Alternative Mrna Splicing In Honey Bees, Pablo Cingolani, Xiaoyi Cao, Radhika S. Khetani, Chieh-Chun Chen, Melissa Coon, Alya'a Sammak, Aliccia Bollig-Fischer, Susan Land, Yun Huang, Matthew E. Hudson, Mark D. Garfinkel, Sheng Zhong, Gene E. Robinson, Douglas M. Ruden

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole …

A Novel Community-Based Study To Address Disparities In Hypertension And Colorectal Cancer: A Study Protocol For A Randomized Control Trial, Joseph Ravenell, Hayley Thompson, Helen Cole, Jordan Plumhoff, Gia Cobb, Lola Afolabi, Carla Boutin-Foster, Martin Wells, Marian Scott, Gbenga Ogedegbe

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Black men have the greatest burden of premature death and disability from hypertension (HTN) in the United States, and the highest incidence and mortality from colorectal cancer (CRC). While several clinical trials have reported beneficial effects of lifestyle changes on blood pressure (BP) reduction, and improved CRC screening with patient navigation (PN), the effectiveness of these approaches in community-based settings remains understudied, particularly among Black men.

Methods/design

MISTER B is a two-parallel-arm randomized controlled trial that will compare the effect of a motivational interviewing tailored lifestyle intervention (MINT) versus a culturally targeted PN intervention on improvement of BP …

Reviewer Acknowledgement 2013, Thomas Liehr, Henry Heng, Yuri Yurov

Wayne State University Associated BioMed Central Scholarship

Contributing reviewers

The editors of Molecular Cytogenetics would like to thank all our reviewers who have contributed to the journal in volume 5 (2012).