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2014

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Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano Jan 2014

Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano

All ETDs from UAB

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Two major factors in both familial and sporadic PD are mitochondrial dysfunction and insufficient autophagy. My thesis research focuses on the interplay between these activities in PD. To investigate the common and differential effects of PD-inducing neurotoxins on mitochondrial bioenergetics and their relationships to cell survival, we used an in vitro culture system, differentiated dopaminergic SH-SY5Y neuroblastoma cells. We found that the neurotoxins rotenone, 1-methyl-4- phenylyridinium (MPP+) and 6-hydroxydopamine (6-OHDA), decreased mitochondrial respiration and induced cell death in these cells. The extent and characteristics of mitochondrial dysfunction in response to …


Regulation Of Skeletal Muscle Plasticity Using Engineered Configurations Of The Transcription Factors Myod And E12, Vladimir Grubisic Jan 2014

Regulation Of Skeletal Muscle Plasticity Using Engineered Configurations Of The Transcription Factors Myod And E12, Vladimir Grubisic

All ETDs from UAB

Skeletal muscle fibers, although terminally differentiated, can change their features, such as contraction speed and endurance, and throughout adult life in response to variety of stimuli, like exercise. This process is called plasticity and is mainly regulated by the type of nerve activity. Over the past several decades, research has shown that the properties of myofibers are also determined during muscle development. Ultimately, the change in phenotype requires a change in gene expression which is, in turn, regulated by transcription factors (TFs). Basic helix-loop-helix (bHLH) TFs regulate myogenesis and the central role belongs to the myogenic differentiation 1 (MyoD), often …


The Role Of Human Ficolin-2 During Invasive Pneumococcal Disease, Allison Marie Brady Jan 2014

The Role Of Human Ficolin-2 During Invasive Pneumococcal Disease, Allison Marie Brady

All ETDs from UAB

Streptococcus pneumoniae (pneumococcus) is a significant human pathogen that typically resides in the nasopharynx of humans. The major virulence factor of pneumococcus is its capsular polysaccharide, of which it can express over 90 unique serotypes. However, there is great disparity in which serotypes colonize or cause disease, though the reason for these differences are not well understood. Serotype 11A is one such serotype that frequently colonizes the nasopharynx of children, but rarely causes disease. Interestingly, serotype 11E, a variant of 11A, varies only in the O-acetylation of a galactose residue in its polysaccharide repeating unit. This difference in structure is …


Determining The Role Of Neuregulin-1 And Its Erbb Receptors In The Pathogenesis Of Malignant Peripheral Nerve Sheath Tumors, Stephanie Brosius Jan 2014

Determining The Role Of Neuregulin-1 And Its Erbb Receptors In The Pathogenesis Of Malignant Peripheral Nerve Sheath Tumors, Stephanie Brosius

All ETDs from UAB

Malignant peripheral nerve sheath tumors (MPNSTs) are the most common cause of death in patients with neurofibromatosis type-1. These aggressive, Schwann cell-derived tumors have no treatment beyond surgical resection. Developing targeted chemotherapeutics remains crucial to improving patient survival. The Schwann cell mitogen neuregulin-1 (NRG1) was shown to mediate the migration, proliferation and survival of MPNSTs. Furthermore, overexpression of NRG1 in Schwann cells (P0-GGF beta 3 mice) on an outbred C57BL/6J x SJL/J background induced the formation of neurofibromas and MPNSTs similar to human disease, yet these mice have intact neurofibromin. To determine if NRG1 acts within the same signaling cascade …


Long-Term Stability Of Maxillary Advancement In Non-Syndromic Cleft Lip And Palate Patients Using The Red Ii System, Jared Adrian Carter Jan 2014

Long-Term Stability Of Maxillary Advancement In Non-Syndromic Cleft Lip And Palate Patients Using The Red Ii System, Jared Adrian Carter

All ETDs from UAB

Objective: The purpose of this study is to evaluate skeletal stability at a minimum of one year following maxillary advancement distraction osteogenesis with the KLS Martin RED II System in non-syndromic CLP patients treated at UAB SOD. Methods: This retrospective cohort study evaluated 20 non-syndromic CLP patients (12 males, 8 females, average age 10.97) treated at the UAB SOD by the same surgeon for maxillary hypoplasia with rigid external distraction using the RED II System (KLS Mar-tin Group, Tuttlingen, Germany). Pre-surgical (T1), post-consolidation (T2), and LTFU (T3) radiographs were digitized and analyzed with via a custom analysis to evaluate treatment …


Cd5-Dependent Ck2 Activation Is Critical For The Maintenance Of B-1a B Cells, Kevin S. Cashman Jan 2014

Cd5-Dependent Ck2 Activation Is Critical For The Maintenance Of B-1a B Cells, Kevin S. Cashman

All ETDs from UAB

CD5 has classically been shown to act as a negative regulator of antigen receptor signaling, however recent evidence has discerned that the CD5 molecule contains a previously undefined cytoplasmic domain which constitutively binds inactive CK2 and facilitates its activation through CD5 ligation. With the development of a mouse model which contains a micro-deletion knock-in form of CD5 which lacks the amino acids necessary to facilitate this CD5-CK2 interaction, it is now understood that CD5 plays a more significant role in cellular physiology than previously appreciated. T cells from this mouse model show increased AICD and dysregulation in T helper subset …


The Role Of Children's Books In Classroom Discourse And Pedagogy, Deborah Bailey Jan 2014

The Role Of Children's Books In Classroom Discourse And Pedagogy, Deborah Bailey

All ETDs from UAB

This qualitative case study explored the factors that contributed to how typical book reading practices and the time spent on book reading were implemented during the school day. Previous research has shown the importance of reading books to young children and that providing access to books has led to reading growth and progress. However, little research has focused on actually identifying how or if books are used during the course of a classroom day. This investigation was conducted in three elementary schools within two school districts in the southeastern United States. Study participants included eight elementary teachers who taught a …


Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet Jan 2014

Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet

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Cryptic epitopes (CE) are a unique set of human leukocyte antigen class I (HLA-I)-restricted peptides that are encoded by alternative reading frames (ARFs) of genes. During human immunodeficiency virus-1 (HIV-1) infection, CE translated from either sense or antisense transcripts elicit epitope-specific CD8 T cell responses. Previous studies using simian immunodeficiency virus (SIV)-vaccinated animals have shown that an increased breadth of CD8 T cell responses is correlated with controlling viral replication, therefore stressing the potential clinical benefit of vaccine-induced T cell responses to a diverse set of viral epitopes. Yet, the genetic profiles and immunological significance of CE remain poorly understood. …


The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black Jan 2014

The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black

All ETDs from UAB

Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can suppress inflammation and autoimmunity in hypercholesterolemic mice by modulating cellular cholesterol homeostasis and lipid oxidation. However, the cellular and molecular mechanisms involved are poorly understood, and whether ApoA-I or ApoA-I mimetic peptides can similarly exert immunosuppressive effects or improve inflammatory organ disease in SLE under normolipidemic conditions remains unresolved. We therefore first took a genetic approach in which bone marrow from SLE-prone Sle123 mice was transferred into wild-type, ApoA-I knockout (ApoA-I-/-) and ApoA-I transgenic (ApoA-Itg) mice. Transgenic expression of ApoA-I suppressed CD4+ T and B lymphocyte activation, reduced …


Examining Neuropsychological Sequelae Of Chronic Pain And The Effect Of Immediate-Release Opioid Analgesics, Cady Block Jan 2014

Examining Neuropsychological Sequelae Of Chronic Pain And The Effect Of Immediate-Release Opioid Analgesics, Cady Block

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Introduction: Patients commonly complain of subjective side effects of opioid use, including forgetfulness, slowed processing speed, confusion, and sedation - which have raised concerns about potential cognitive impairment. However, research on the effects of opioids on objective neuropsychological performance is thus far equivocal and, unfortunately, many of the studies cited as support for opioid-related impairment do not fully account for the neuropsychological effects of chronic pain, which has been shown to affect many of the same neuropsychological domains purported to be affected by opioids. To that end, we sought to examine whether: 1) chronic nociceptive pain itself results in objective …


The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser Jan 2014

The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser

All ETDs from UAB

Neonatal late-onset sepsis is invasive infection occurring after the first 48 hours of life, and one of the leading causes of death among preterm infants in the United States and abroad. Infections with Gram-negative bacteria, such as Klebsiella pneumonia, occurring when bacteria translocate across premature gut epithelium into the bloodstream, can be particularly severe. Preterm infants in the neonatal intensive care unit undergo intense antibiotic regimens due to high risk of infection. Paradoxically, prolonged exposure of preterm infants to empiric antibiotic therapy early in the hospital stay is associated with increased risk of intestinal infection and death after adjustment for …


Glycine Supplementation To Improve Insulin Sensitivity In Humans, Marie-Hippolyte Boni Epse Attobla Jan 2014

Glycine Supplementation To Improve Insulin Sensitivity In Humans, Marie-Hippolyte Boni Epse Attobla

All ETDs from UAB

The main purpose of this pilot study was to investigate the insulin sensitizing effect of glycine as a dietary supplement in insulin resistant (IR) normoglycemic subjects (N= 10), and to determine significant changes in insulin sensitivity and lipid profile after four weeks of glycine supplementation. Descriptive statistics were used to describe the basic characteristics of the study population. A paired t-test was used to determine differences between insulin sensitivity and lipid profile pre- and post- intervention, considering the estimation of HOMA-IR and Matsuda- index scores. Results showed that glycine supplementation might improve triglyceride (TG) levels in European Americans; and low-density …


Exposure To Methylmercury Via Fish Consumption In Ghana And An Evaluation Of Methylmercury Toxicity Under A Low Food Ration In Daphnia Pulex, Dzigbodi Adzo Doke Jan 2014

Exposure To Methylmercury Via Fish Consumption In Ghana And An Evaluation Of Methylmercury Toxicity Under A Low Food Ration In Daphnia Pulex, Dzigbodi Adzo Doke

All ETDs from UAB

For many people of the world, fish is a primary source of protein, especially in countries like Ghana, where about 60% of the protein consumed is derived from fish. Fish advisories have been established by some nations to protect the public from harmful health effects linked to eating contaminated fish. Methylmercury (MeHg) is one such contaminant that has resulted in fish advisories. Fish advisories have not been developed in Ghana, although MeHg contamination of aquatic ecosystems is likely due to the long history of mercury (Hg) use in artisanal gold mining. To address this gap in our knowledge, I compiled …


Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin Jan 2014

Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin

All ETDs from UAB

Ovarian cancer while the second most common gynecologic malignancy is the most commons cause of death due to a gynecologic malignancy and the fifth most common cause of death to cancer in women. In 2014, there will be an expected 21,980 cases and 14,270 deaths. Unfortunately, the five-year survival for ovarian cancer is only 40% and this has barely increased over the past 30 years. New approaches need to be developed in order to study ovarian cancer and identify methods of overcoming chemotherapy resistance. This dissertation presents the work conducted in the development of a patient-derived xenograft model of ovarian …


The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha Jan 2014

The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha

All ETDs from UAB

Outflow Tract (OFT) malformations underlie a majority of congenital heart defects (CHD) in humans and are a leading cause of childhood mortality. The OFT, which gives rise to the aorta and pulmonary artery of the heart, relies on the contribution of the Second Heart Field (SHF) progenitors in the pharyngeal and the splanchnic mesoderm, outside of the initial heart. OFT morphogenesis requires highly regulated SHF development involving the proliferation, differentiation and deployment of the SHF progenitors to the heart. Extensive studies elegantly demonstrate how transcriptional networks integrating signaling input from multiple pathways finely balance the proliferation and differentiation of SHF …


Modulation Of The Immune Response To Aspergillus Fumigatus By Antibodies To Conserved Bacterial Polysaccharides, Emily Stefanov Jan 2014

Modulation Of The Immune Response To Aspergillus Fumigatus By Antibodies To Conserved Bacterial Polysaccharides, Emily Stefanov

All ETDs from UAB

The incidence of asthma, allergies and autoimmune diseases has increased dramatically in developed countries. The hygiene hypothesis postulates that excessively sanitary conditions lead to a lack of critical immune stimulation during early life, leading to inappropriate responses to self or harmless antigens later in life. Many bacteria and potential allergens share common polysaccharide epitopes. We investigated the ability of antibodies against these shared polysaccharides to dampen the immune response to the ubiquitous fungus and potent allergen, Aspergillus fumigatus. We found that antibodies against these polysaccharides, specifically of the IgM isotype, induced by neonatal bacterial immunization or passive antibody transfer, dampened …


Neuroplastic Change In Adults With Hemiparetic Multiple Sclerosis Following Constraint-Induced Movement Therapy, Chelsey Sterling Jan 2014

Neuroplastic Change In Adults With Hemiparetic Multiple Sclerosis Following Constraint-Induced Movement Therapy, Chelsey Sterling

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Constraint-Induced Movement (CI) therapy has been found to produce substantial improvements in upper-extremity functioning in both adults and children following damage to the central nervous system (CNS), including stroke, traumatic brain injury and cerebral palsy. In addition, structural changes in the sensorimotor cortices and bilateral hippocampi have been observed in both adults and children following CI therapy treatment for upper extremity hemiparesis. Although most research has been conducted in patients with such static injuries as strokes and TBI, clinical efficacy of CI therapy has also been demonstrated in a small number of patients with the progressive autoimmune disorder, multiple sclerosis …


Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell Jan 2014

Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell

All ETDs from UAB

The electrogenic Na/bicarbonate cotransporter (NBCe1) is an acid/base regulator that is also involved in coordinating epithelial ion transport. Splice variants of NBCe1 differ at their cytosolic amino- (N-) and/or carboxy- (C-) termini. These different cytosolic termini impart differential regulation for each variant. For example, the N-terminus of NBCe1-A is autostimulatory, whereas the N-terminus of NBCe1-B and -C is autoinhibitory. We examine the regulatory role of PIP2 for NBCe1 splice variants. In the first study of this dissertation, we characterize the effect of increasing PIP2 on the activity of NBCe1-A, -B, and -C expressed in Xenopus laevis oocytes. Injecting PIP2 stimulated …


Validation Of A Cytometric Bead-Based Immunoassay For Tear Interleukin 8 And Interferon Gamma Inducible Protein 10, My-Tho Karin Tran Jan 2014

Validation Of A Cytometric Bead-Based Immunoassay For Tear Interleukin 8 And Interferon Gamma Inducible Protein 10, My-Tho Karin Tran

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ABSTRACT Background Interleukin 8 (IL-8) and Interferon gamma inducible protein 10 (IP-10) are pro-inflammatory chemokines that may play key antagonistic roles in regulating corneal immune privilege and angiogenesis prevention. Some groups have reported that tear levels of IL-8 and IP-10 measured by multiplexed antibody-based assay are artifact prone and therefore unreliable, leading to their under-utilization as ocular surface disease and dry eye biomarkers. The current study compares tear levels of IL-8 and IP-10 measured by multiplexed cytometric bead-based assay (CBA) with single analyte ELISA assay. Mass spectrometry, a non-antibody based method, was also used to obtain confirmation of tear levels. …


Peripheral Neuropathy In The Teetering Mice Results From Mutation Of The Escrt Component Hrs, Jennifer Ashley Watson Jan 2014

Peripheral Neuropathy In The Teetering Mice Results From Mutation Of The Escrt Component Hrs, Jennifer Ashley Watson

All ETDs from UAB

The sorting and degradation of endocytosed cargo by the endosome regulates many cellular functions common to all cells. Neural cells appear to be particularly vulnerable to perturbation in endo-lysosomal transport, and several neurological disorders are caused by a primary deficit in this pathway. In this dissertation, I show that the spontaneously occurring neurological mutation teetering (tn) is a single nucleotide substitution in the endosomal cargo-sorting component hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs) that reduces the abundance of HRS. By 3 weeks of age, the tn mice exhibit heightened pain sensitivity, muscle weakness and reduced muscle size. The loss of …


Using Neuroimaging To Predict Treatment Response In Patients With Schizophrenia, Nathan Lyle Hutcheson Jan 2014

Using Neuroimaging To Predict Treatment Response In Patients With Schizophrenia, Nathan Lyle Hutcheson

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Schizophrenia is a severe debilitating mental illness that affects approximately 1% of people worldwide. Compared to healthy controls (HC), patients with schizophrenia (SZ) have memory deficits, specifically prominent disruptions in their episodic memory. These memory disruptions are thought to be caused by altered structure and function of areas within the memory network, specifically the prefrontal and temporal lobe including the hippocampus. Recently, identifying biomarkers of treatment response by using neuroimaging has become a prominent area of interest in schizophrenia. Biomarkers in schizophrenia could help by allowing for more efficient treatment using current method and also the development of novel treatments. …


Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza Jan 2014

Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza

All ETDs from UAB

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and are the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective resulting in a high rate of MPNST recurrence and poor five year patient survival. This necessitates the exploration of alternative chemotherapeutic options for MPNST patients. By evading apoptosis and utilizing protective mechanisms such as autophagy, cancer cells develop resistance to chemo- and radio-therapy. The overall goal of my thesis studies is to evaluate chemotherapeutic agents that can modulate both apoptosis and autophagy, thus target both cell death pathways …


Development Of An Axonal Outgrowth Assessment Methodology For Dorsal Root Ganglia Explants And Demonstration Of Method Efficacy On Electrospun Polymer Scaffolds, Sarah Margaret Kezar Jan 2014

Development Of An Axonal Outgrowth Assessment Methodology For Dorsal Root Ganglia Explants And Demonstration Of Method Efficacy On Electrospun Polymer Scaffolds, Sarah Margaret Kezar

All ETDs from UAB

In chronic spinal cord injury (SCI), a glial encapsulated cyst develops at the injury site and acts as a physical and biochemical barrier to regeneration. Discussion has suggested that filling the cyst with a growth promoting scaffold is a promising approach to cure chronic SCI, though the research to date lacks a systematic approach. Dorsal root ganglia (DRG) explants are an extremely common tissue culture model of neural regeneration employed in this field, however there is no uniform method for objectively quantifying substrate biocompatibility and neurite outgrowth. Therefore, we aimed to develop a novel DRG growth assessment methodology and to …


Contribution Of Hyperactive Glycogen Synthase Kinase-3 (Gsk3) To Impaired Neurogenesis And Cognition In Mice, Margaret Kimbrough King Jan 2014

Contribution Of Hyperactive Glycogen Synthase Kinase-3 (Gsk3) To Impaired Neurogenesis And Cognition In Mice, Margaret Kimbrough King

All ETDs from UAB

The overall goals of this research were to examine the regulatory actions of glycogen synthase kinase-3 (GSK3) in adult mouse hippocampal neurogenesis and in mouse cognitive functions in order to gain further insight regarding the function of GSK3 in the healthy and diseased central nervous system. Focusing on differences between male and female mice, we found that hippocampal neurogenesis was impaired by hyperactive GSK3 in both sexes, but was improved by environmental enrichment in male, but not female, mice. Chronic stress reduced neurogenesis in male mice, but not in female mice. Environmental enrichment and chronic stress inhibited, and activated, respectively, …


The Direct Effects And Vertical Transfer Of Carbonaceous And Metal-Loaded Hydrochars In Aquatic Organisms, Katie Lauren Kohlenberg Jan 2014

The Direct Effects And Vertical Transfer Of Carbonaceous And Metal-Loaded Hydrochars In Aquatic Organisms, Katie Lauren Kohlenberg

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Industrial use of reactive micro- and nano-sized carbonaceous hydrochar (CH) is expanding rapidly. These carbonaceous particulates are synthesized by the pyrolysis of biomass in an industrial process called hydrothermal carbonization (HTC) and have gained attention as a soil conditioner. Additionally, the HTC process is being expanded to coat heavy-metal nanoparticles, such as nano-copper and nano-iron, to prevent surface oxidation of these metals. These carbonaceous particles are likely to undergo secondary reactions with metals, toxicants, or other compounds. There is potential for these carbonaceous particulates to enter watersheds and have deleterious effects on aquatic food web dynamics. In this study, we …


Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li Jan 2014

Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li

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Alzheimer disease (AD) is a devastating neurological condition that slowly destroys memory and thinking skills of the affected patients. No disease-modifying medications are available. While all the treatment against Aߒ (major component of one hallmark pathology of AD) failed in clinical trials, tau (major component of the other hallmark pathology of AD) is emerging as a better alternative. Germline knockout of tau does not cause overt abnormalities in young mice and prevents AD-like deficits in mouse models of AD. Germline knockout of tau also confers resistance to epileptiform activity in models of both AD and epilepsy. Therefore tau is proposed …


Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li Jan 2014

Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li

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Systemic lupus erythematosus (SLE) is characterized by elevation of type I interferon (IFN) signature genes and production of autoantibodies against apoptotic self-antigens. The complex nature of SLE, however, suggests that multiple immune dysregulations must integrate to initiate the disease. Here, we provided evidence that lupus can be initiated via type I IFNs-induced follicular translocation of membrane lymphotoxin (mLT)-expressing marginal zone (MZ) B cells in the spleen of lupus prone BXD2 mice. The mislocation of mLT+ MZ B cells induces two important pathogenic effects including deteriorations of marginal zone macrophages (MZMs) in the MZ, leading to defective clearance of apoptotic debris, …


Anatomical And Neurochemical Investigation Of The Brain In Autism, Lauren E. Libero Jan 2014

Anatomical And Neurochemical Investigation Of The Brain In Autism, Lauren E. Libero

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with widespread behavioral symptoms and a strong neurobiological origin. Neuroimaging studies of ASD have uncovered evidence for widespread abnormalities in brain anatomy and functioning. Abnormalities reported by structural brain imaging, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) studies have aided in characterizing ASD as a complex, systems-wide disorder. The overarching goal of this project was to use multiple modalities of neuroimaging to investigate the underlying neural mechanisms of ASD. The following techniques were used to collect and analyze multimodal neuroimaging data from a relatively large number of participants …


Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin Jan 2014

Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin

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White adipose tissue (WAT) releases fatty acids from stored triacylglycerol (TAG) for energy source. Here, we report that null mice for KH-type splicing regulatory protein (KSRP), an RNA-binding protein, resisted high fat diet (HFD) induced obesity. Target of deletion of KSRP regulates gene expression at multiple levels and enhances lipolysis in epididymal WAT (eWAT) due to up-regulation of genes promoting lipolytic activity. Expression of miR-145 is decreased due to impaired pri-miR-145 processing in Ksrp-/- eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals …


Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker Jan 2014

Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker

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Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …