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Pathogenesis, Molecular Genetics, And Genomics Of Mycobacterium Avium Subsp. Paratuberculosis, The Etiologic Agent Of Johne’S Disease, Govardhan Rathnaiah, Denise K. Zinniel, John P. Bannantine, Judith R. Stabel, Yrjo T. Grohn, Michael T. Collins, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s disease in ruminants causing chronic diarrhea, malnutrition, and muscular wasting. Neonates and young animals are infected primarily by the fecal–oral route. MAP attaches to, translocates via the intestinal mucosa, and is phagocytosed by macrophages. The ensuing host cellular immune response leads to granulomatous enteritis characterized by a thick and corrugated intestinal wall. We review various tissue culture systems, ileal loops, and mice, goats, and cattle used to study MAP pathogenesis. MAP can be detected in clinical samples by microscopy, culturing, PCR, and an enzyme-linked immunosorbent assay. There are commercial …

Ccpa Affects Infectivity Of Staphylococcus Aureus In A Hyperglycemic Environment, Markus Bischoff, Bodo Wonnenberg, Nadine Nippe, Naja J. Nyffenegger-Jann, Meike Voss, Christoph Beisswenger, Cord Sunderkotter, Virginie Molle, Quoc Thai Dinh, Frank Lammert, Robert Bals, Mathias Herrmann, Greg A. Somerville, Thomas Tschernig, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA). Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections. In hyperglycemic individuals, the bacterium Staphylococcus aureus causes serious, life-threatening infections. The importance of CcpA in regulating carbon catabolite repression in S. aureus suggests it may be important for infections in hyperglycemic individuals. To test this suggestion, hyperglycemic non-obese diabetic (NOD; blood glucose level ≥20 mM) mice were challenged with the …

Back Of The Envelope Calculations Regarding Alexandrov, Et Al. 2009, F. Matthew Mihelic

Faculty Publications

The paper entitled “DNA Breathing Dynamics in the Presence of a Terahertz Field” written by Alexandrov, Gelev, Bishop, Usheva, and Rasmussen that was posted on the Physics ArXiv on October 28, 2009, dealt with the effects of terahertz electromagnetic radiation on the DNA molecule. Figure 4 of the paper indicates that a segment of DNA that is between 60 and 70 base pairs in length will develop a “bubble” (i.e. separation of the hydrogen bonds between base pairs) at a location of about 45 base pairs, when exposed to 2 THz electromagnetic radiation for a time period of at least …

การเสื่อมวอลเลอเรียนในโรคสมองขาดเลือดเฉียบพลันถึงกึ่งเฉียบพลันแสดงโดยภาพดิฟฟิวชันเทนเซอร์, วสุนนท์ ธินรุ่งโรจน์

Chulalongkorn University Theses and Dissertations (Chula ETD)

วัตถุประสงค์: งานวิจัยชิ้นนี้ทำเพื่อศึกษาการเสื่อมวอลเลอเรียนของใยประสาทโดยใช้การตรวจภาพถ่ายสมองด้วยคลื่นแม่เหล็กโดยใช้เทคนิคการกระจายของโมเลกุลน้ำและเพื่อศึกษาความสัมพันธ์ของดัชนีการกระจายของโมเลกุลน้ำกับการฟื้นตัวของระบบประสาทสั่งการของผู้ป่วยสมองขาดเลือด ทั้งนี้ เพื่อที่จะนำผลการศึกษาไปใช้พยากรณ์โรคในผู้ป่วยโรคสมองขาดเลือด วิธีการศึกษา: รูปแบบการศึกษาเป็นแบบ prospective analytic study โดยรวบรวมผู้ป่วยโรคสมองขาดเลือดจำนวน 12 ราย โดยทำการเก็บข้อมูลการฟื้นตัวของระบบประสาทสั่งการจากแบบประเมิน Fugh-Meyer และตรวจภาพสมองด้วยคลื่นแม่เหล็กโดยใช้เทคนิคการกระจายตัวของโมเลกุลน้ำที่เวลาแรกรับ ที่เวลา 1 เดือน และที่เวลา 3 เดือน จากนั้นทำการเปลี่ยนข้อมูลให้เป็นดัชนีการกระจายของโมเลกุลน้ำด้วยวิธี region base analysis และ tract base spatial statistical analysis (TBSS) จากนั้นหาความสัมพันธ์ของดัชนีการกระจายของน้ำกับการฟื้นตัวของระบบประสาทสั่งการจากแบบประเมิน Fugh-Meyer ด้วย Spearman correlation coefficient และใช้ Mann-Whitney U test เพื่อเปรียบเทียบความแตกต่างกันของดัชนีการกระจายของน้ำระหว่างฐานสมองข้างที่ขาดเลือดและฐานสมองข้างที่ไม่ขาดเลือด ผลการศึกษา: พบความสัมพันธ์ของค่า FA ที่เวลา 90 วัน กับการฟื้นตัวของระบบประสาทสั่งการของรยางค์บนที่เวลาแรกรับ (r = 0.678 p value = 0.45 ) พบความสัมพันธ์ของค่า FA ที่เวลา 90 วัน กับการฟื้นตัวของระบบประสาทสั่งการของรยางค์บน, รยางค์ล่าง และการประเมินโดยรวม จากการประเมินด้วย FMA ที่เวลา 1 เดือน (r = 0.833 p value = 0.01, r = 0.765 p value = 0.02, r=0.817 p value = 0.01 ตามลำดับ) พบความสัมพันธ์ของค่า FA ที่ 3 เดือนกับการฟื้นตัวของระบบประสาทของรยางค์บน และการประเมินโดยรวม จากการประเมินด้วย FMA ที่เวลา …

Characterization Of Spinal Cord Injury And Spinal Cord Injury Induced Neuropathic Pain, Amanda Mohaimany-Aponte

All ETDs from UAB

Spinal cord injury (SCI) affects between 40 and 80 million people globally. Within the United States over 400,000 individuals live with SCI, and annually over 17,000 individu-als are added to this population. SCI patients are afflicted with a myriad of issues, one of which being SCI induced neuropathic pain (SCI-NP). Up to 80% of SCI patients go on to develop SCI-NP, which has been shown to last chronically and present itself as evoked pain, spontaneous pain, or a combination of both. SCI-NP is a top concern for SCI pa-tients, often listed before functional recovery. SCI-NP has been shown to greatly …

Identification Of The Microrna Mir-101a And Its Target Ezh2 As Contributors To Rodent Anxiety-Like Behavior, Joshua Cohen

All ETDs from UAB

Anxiety disorders are the most commonly diagnosed mental illness in the United States. Yet current treatment options are of limited efficacy, resulting in chronic disability for many patients. A greater mechanistic understanding of the neural states that cause anxiety behavior is necessary to develop better treatments for anxiety disorders. Since rodent models provide greater opportunity for investigating cellular and molecular under-pinnings of anxiety-like behavior, the present studies utilized rats bred for High Response to novelty (High Responders, HRs) and Low Response to novelty (Low Responders, LRs) which naturally exhibit low and high levels of anxiety respectively. Because the HR/LR anxiety …

Tgf-Β Regulates The Stability Of Sox9 In Cartilage, George Coricor

All ETDs from UAB

One out of two people in the U.S. will experience some form of Osteoarthritis (OA) in their lifetime. Members of the Transforming Growth Factor-β (TGF-β) superfamily are important factors that stimulate chondrocyte matrix biosynthesis. Mice with a dominant-negative mutation of the TGF-βIIR develop a degenerative joint disease resembling OA. Another key chondrogenic factor, SOX9, is important for maintaining chondrocyte function. SOX9 and TGF-β receptors are decreased in OA patients. Our overall hypothesis is that TGF-β regulates SOX9 to maintain articular cartilage. We utilized two cell culture models for these experiments, ATDC5 cells, and primary bovine articular chondrocytes. We showed that …

Elucidating The Cellular Function Of The N-Terminal Domain Of Tyrosyl-Dna Phosphodiesterase I, Selma Marcela Cuya

All ETDs from UAB

Tyrosyl-DNA phosphodiesterase I (Tdp1) is a conserved eukaryotic DNA repair enzyme that removes adducts from DNA-ends. This includes DNA topoisomerase I (Top1)-DNA covalent complexes reversibly stabilized by camptothecins (CPTs). Tdp1s two-step catalytic cycle requires the action of its nucleophilic histidine (Hisnuc) that detaches the adduct by forming a Tdp1-DNA adduct, and its general acid/base histidine (Hisgab) to activate water, thereby releasing Tdp1 from the DNA-end. Tdp1 expression is associated with genomic instability, cancer etiology, chemotherapeutic resistance, and SCAN1-neurodegeneration, via Tdp1HisgabArg catalytic mutant. Our lab has characterized substitutions of the catalytic histidines in both yeast and human cell models. These substitutions …

Cd8+ T Lymphocyte Responses To Persistent Murine Cytomegalovirus Infection Of The Central Nervous System, Kristine Valenteros

All ETDs from UAB

Cytomegalovirus (CMV) is the most frequent cause of congenital brain abnormalities and can lead to lifelong neurological sequalae. Although the brain is a major target in congenital CMV infection, little is known about the long-term effects of infection of the central nervous system (CNS) following acute infection and the resulting neuroimmune responses involved. Due to species-specificity of HCMV, we use a mouse model to study the pathogenesis of HCMV infection of the developing CNS. Newborn mice peripherally infected with murine CMV (MCMV) develop high levels of viremia and subsequent productive infection in the brain parenchyma. CD8+ T lymphocytes are essential …

Characterization Of Molecular Pathways Involved In The Production Of Class-Switched Antibodies, Arthur James Vanvalkenburg

All ETDs from UAB

This dissertation research describes two independent characterizations of molecular pathways involved in the manufacture of class-switched antibodies and differentiation of B cells involving the adaptor protein Hematopoietic SRC Homology 2 Domain-containing protein (HSH2) and the surface molecule CD19. HSH2 is dynamically expressed in different subsets of B cells, showing high expression in B1 and MZ B cells and low expression in GC B cells. Experiments involving HSH2 transgenic mice have determined that HSH2 may act as a rheostat regulating the production of class-switched antibodies. Various factors that stimulate B cell activation and differentiation induce HSH2 expression, although regulation of HSH2 …

The G Protein-Coupled Estrogen Receptor (Gper) Mediates Estrogen-Induced Regulation Of Heart Rate By Modulating Thyroid Hormone Levels In Zebrafish Embryos, Shannon Nicole Romano

All ETDs from UAB

Estrogens regulate cell signaling and gene expression by binding to nuclear estrogen receptors (ERs) alpha and beta (ERα, ERβ), ligand-dependent transcription factors. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. In the cardiovascular system, estrogens regulate vessel pressure and exert cardioprotective effects on the vasculature. However, whether estrogens act directly to modulate heart function, and the mechanism by which this occurs is not well understood. Therefore, the overall goals of this dissertation were to (1) determine if estrogen receptor ligands modulate heart rate and to (2) determine the …

Ca2+-Independent Phospholipase A2 Beta-Derived Lipid Signals And Osteogenesis, William Hancock

All ETDs from UAB

Bone modeling can be modulated by lipid signals and arachidonic acid (AA); its cyclo-oxygenase 2 (COX2) metabolite, prostaglandin E2 (PGE2), is an important mediator of optimal bone formation. Hydrolysis of AA from membrane glycerophospholipids is catalyzed by phospholipases A2 (PLA2s). We reported that mice deficient in the Ca2+-independent PLA2beta (iPLA2β), encoded by PLA2G6, have decreased bone formation, relative to wild type (WT) mouse bones. Here, we examined at the mechanistic and molecular levels the role of iPLA2β in bone formation using bone marrow stromal cells and calvarial osteoblasts from WT and iPLA2β-deficient mice and MC3T3-E1 osteoblast precursor cell line. Our …

The Use Of Web Computing To Solve Modern Data Problems In Science And Medicine, Alex M. Dussaq

All ETDs from UAB

Modern day research in science and medicine has become dominated by the ideas of 'Big Data'. Life science data have become progressively more complex and the rate at which it is generated continues to accelerate. This combination of complexity and genera- tion speed creates a multitude of informatics problems to solve. We believe that among the many issues facing modern data scientists, there exists a substantial subset that can only be satisfactorily solved utilizing web computing. Of these web specific issues, we have chosen to focus primarily on data storage and retrieval, data privacy, and data visualization. We present here …

A Tissue Engineering Approach To The Development Of A 3d Breast Carcinoma Surrogate, Kayla Goliwas

All ETDs from UAB

Tumors are three dimensional tissues consisting of malignant cells and various stromal cell populations within a volume of extracellular matrix. These components form an intricate network that influences many facets of tumor biology. Paracrine interactions between tumor cells and the surrounding microenvironment can alter drug response and impact therapeutic efficacy in vivo, yet most current in vitro models do not accurately recapitulate the stromal microenvironment or associated dimensionality of human tumors. In vitro models that are more representative of the human tumor microenvironment, including a more recapitulative dimensionality and cellular composition, have broad utility in the evaluation of mechanisms driving …

Purification, Characterization, And Enzymatic Activity Of Human Cytosolic Sulfotransferase 1c4, Amber Lynn Guidry

All ETDs from UAB

Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3’-phosphoadenosine-5’-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate’s biological activity and increasing the compound’s water solubility. While several of the hSULTs’ endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown. The fetal expression of hSULT1C4 leads to the hypothesis that the function of this enzyme may be to regulate metabolic and hormonal signaling molecules, such as estrogenic compounds, that may be generated or consumed by the …

Development And Assessment Of Nonsense Suppression Therapies To Ameliorate Disease Progression In A Nonsense Mouse Model Of Mps I Hurler Syndrome, Gwendolyn G. Gunn

All ETDs from UAB

Nonsense mutations introduce a premature termination codon (PTC) into the open reading frame of an mRNA resulting in premature translation termination, loss of functional protein, and rapid degradation of the mutant mRNA. Approximately 11% of human genetic disorders are attributable to a nonsense mutation. Several small molecules have been identified as potential nonsense suppression compounds. These compounds increase the frequency of PTC recognition by near-cognate aminoacyl tRNAs resulting in PTC “readthrough” and restored protein production. Mucopolysaccharidosis type I-Hurler (MPS IH) is the severe form of the autosomal recessive lysosomal storage disorder caused by mutations in the iduronidase (IDUA) gene. 60-80% …

Phenomic And Metabolomic Analysis Of Chronological Aging In Saccharomyces Cerevisiae, Haley Albright

All ETDs from UAB

Systematic investigation of chronological lifespan (CLS) in the Saccharomyces cerevisiae yeast gene knockout and knockdown (YKO/KD) strains reveals genes, path-ways, and interactions of potential relevance for aging of all eukaryotic cell types. Growth curves obtained by quantitative high-throughput cell array phenotyping (Q-HTCP) of the entire YKO/KD strain collection provide comprehensive snapshots of the influence of each individual gene on CLS. Yeast CLS is also influenced by media com-position, auxotrophic background, and media buffering. We used Q-HTCP to analyze CLS of the YKO/KD libraries, focusing on the interaction between gene networks and media buffering, with respect to their influence on CLS. …

Advances In The Creation And Use Of Genetically Modified Rodent Models, Laura Lambert

All ETDs from UAB

Rodents have been the model of choice for decades in biomedical research due to their relatively high physiological similarity to humans and amenability to genomic modification. While transgenic constructs were first used in mouse blastocysts in 1974 and the first mouse embryonic stem (ES) cell line created in 1981, the lack of reliable methods to produce ES cells or culture embryos from the rat led to the limitation of its use in spite of several advantages such as larger size and higher genetic homology with humans. Use of genetic modification has recently expanded due to the advent of tailored nucleases …

Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone

All ETDs from UAB

Sepsis is the most frequent cause of death of hospitalized patients in modern ICUs. Severe infection, trauma, hemorrhage, burns, and surgery are significant causes of multi-organ injury and immune dysfunction that in turn primes for a high risk of secondary lung infections. In addition to detrimental inflammation, sepsis is linked to loss of metabolic plasticity due to mitochondrial dysfunction in immune cells and lung tissue. In particular, mitochondrial failure in lungs of critically ill septic patients is correlated with high mortality rates. We proposed that AMP-activated protein kinase (AMPK) activation, a major bioenergetic sensor and metabolic regulator, is a plausible …

Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd

All ETDs from UAB

Tumor microenvironments can promote stem cell maintenance, tumor growth, and therapeutic resistance, findings linked by the tumor initiating cell hypothesis. The ischemic microenvironment characterized by low oxygen and glucose, and acidic stress occurs in both solid tumors and non-neoplastic tissue injury. Standard of care for glioblastoma (GBM) includes the chemotherapy temozolomide, which is not curative due, in part, to residual therapy-resistant brain tumor initiating cells (BTICs). Temozolomide efficacy may be increased by targeting carbonic anhydrase 9 (CAIX), a hypoxia and acidic stress responsive gene important for maintaining the altered pH gradient of tumor cells. Using patient-derived GBM xenograft cells, we …

The Impact Of Mitochondrial Genetic Background On Development Of Complex Multifactorial Diseases, Alexander Wendell Bray

All ETDs from UAB

Complex multifactorial diseases such as cardiovascular disease (CVD) and cancer are a pervasive and inescapable component of modern society. However, the genetic elements that modulate individual susceptibility to these diseases remain poorly defined. Excessive mitochondrial oxidant production has been implicated in the initiation and progression of both CVD and cancer. Moreover, polymorphisms inherited on the mitochondria genome appear to influence mammalian mitochondrial function and oxidant generation. In the present study, mitochondrial-nuclear-eXchange (MNX) mice were used to directly assess the contribution of mitochondrial DNA (mtDNA) polymorphisms to atherosclerosis in the apoE deficient (apoE-/-) mouse model of hypercholesterolemia induced atherogenesis. ApoE-/- mice …

Understanding The Mechanism Of Oxidative Stress Generation By Oxidized Dopamine Metabolites: Implications In Parkinson's Disease, Nihar Mehta

Wayne State University Dissertations

Oxidation of dopamine to toxic metabolites is considered to be one of the prime factors involved in the death of dopaminergic neurons in Parkinson’s disease. Some dopamine oxidation products have the capability to redox cycle in the presence of molecular oxygen, further contributing to oxidative stress. Therefore, our aim here was to study the redox cycling of dopamine oxidized metabolites and elucidate the underlying mechanism by which they cause oxidative stress.

Redox reactions involve transfer of one or more electrons between two compounds

resulting in either oxidation or reduction. In redox cycling, a compound undergoes

alternate oxidation and reduction, transferring …

Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki

Wayne State University Dissertations

The work of this project was to develop, test and characterize a potential novel mouse model of the neurodegenerative disease Multiple Sclerosis (MS). Historically, MS has been identified as a primary autoimmune disease of the central nervous system (CNS). However, treatments based on this view have met with limited success, and in most cases, fail to prevent progression of MS from mild to moderate and severe forms. Original observations regarding axonal and neuronal pathology in the white and gray matter of the CNS were rediscovered in the 1990s. These observations indicated that even in the absence of the immune system, …

Estimating The Variables Of The Nonlinear Dynamical Theory Of Acute Cell Injury, Fika Tri Anggraini

Wayne State University Dissertations

This Dissertation is the first to estimate the variables D and S of the nonlinear theory of acute cell injury in hippocampal regions CA1 and CA3 using a rat model of global brain ischemia and reperfusion (I/R). D was estimated by quantifying protein aggregates using ubiquitin Western blotting. S was estimated by quantifying changes in polysomal mRNAs as measured by microarray chips. D and S time courses were sampled at 0.5, 8, 16, 24, 48, and 72 hrs of reperfusion after 10 min brain ischemia. CA1 dies and CA3 survives. The theory predicts D will be larger in CA1 and …

Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan

Theses and Dissertations

DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic …

A Systems Biology Approach For Predicting Essential Genes And Deciphering Their Dynamics Under Stress In Streptococcus Sanguinis, Fadi El-Rami

Theses and Dissertations

Infectious diseases are the top leading cause of death worldwide. Identifying essential genes, genes indispensable for survival, has been proven indispensable in defining new therapeutic targets against pathogens, major elements of the minimal set genome to be harnessed in synthetic biology, and determinants of evolutionary relationships of phylogenetically distant species. Thus, essentiality studies promise valuable revenues that can decipher much of biological complexities.

Taking advantage of the available microbial sequences and the essentiality studies conducted in various microbial models, we proposed a framework for the prediction of essential genes based on our experimentally verified knowledge of the pathways involved in …

Characterization Of The Role Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) Using A Genetic Knockout Mouse Model, Maaged A. Akiel

Theses and Dissertations

In the US, the incidence and mortality rates of hepatocellular carcinoma (HCC) are alarmingly increasing since no effective therapy is available for the advanced disease. Activation of IGF signaling is a major oncogenic event in diverse cancers, including HCC. Insulin-like growth factor binding protein-7 (IGFBP7) inhibits IGF signaling by binding to IGF-1 receptor (IGF-1R) and functions as a potential tumor suppressor for hepatocellular carcinoma (HCC). IGFBP7 abrogates tumors by inducing cancer-specific senescence and apoptosis and inhibiting angiogenesis. We now document that Igfbp7 knockout (Igfbp7-/- ) mouse shows constitutive activation of IGF signaling, presents with pro-inflammatory and immunosuppressive microenvironment, and develops …

Novel Orally Active Hydrogen Sulfide-Releasing Compound, Sg1002, Improves Left Ventricular Function And Survival In A Murine Model Of Ischemic Cardiomyopathy, Bharat Balan

Theses and Dissertations

Hydrogen sulfide (H₂S) is a gasotransmitter that has shown cardioprotective effects in the setting of myocardial injury such as acute myocardial infarction (MI) and pressure overload-induced heart failure. However, there are shortcomings in precision and control release from the use of traditional formulations of H₂S in the form of inorganic salts. In this thesis, we sought to determine if the novel, orally active, slow-releasing H₂S-compound SG1002 plays a role in attenuating MI-induced left ventricular (LV) dysfunction and adverse remodeling. We also evaluated the effect of SG1002 on changes in ECG parameters such as QT …

Vitamin D Receptor Variants And Uncontrolled Asthma, Conor Kerley, Katrina Hutchinson, John Faul, Peter Greally, David Coghlan, Basil Elnazir, Michael Louw, Yury Rochev

Articles

BACKGROUND: Asthma is a common childhood respiratory disease, affecting around 20% of Irish children. In other populations, vitamin D receptor (VDR) polymorphisms have been associated with asthma risk. We aimed to investigate the association between 2 VDR polymorphisms and uncontrolled paediatric asthma. METHODS: 44 asthmatic children and 57 healthy volunteers were studied. The VDR TaqI gene variant in exon 9 (T/C) (rs731236) and ApaI (rs7975232) in intron 8 (C/T) were determined, using TaqMan®Assays. The lung function, serum 25-hydroxyvitamin D (25OHD) levels and other biomarkers of allergy, immunity, airway and systemic inflammation were assessed. RESULTS: The distribution of T and C …

The Actin-Severing Protein Cofilin Is Downstream Of Neuregulin Signaling, Is Regulated By The Tumor Suppressor Merlin, And Is Essential For Schwann Cell Myelination, Nicklaus Sparrow

Electronic Theses and Dissertations

Myelination is a complex process requiring coordination of directional motility and an increase in Schwann cell (SC) size to generate a multi-lamellar myelin sheath. Regulation of actin dynamics during myelination is poorly understood. However, it is known that myelin thickness is related to the abundance of neuregulin1-type III (NRG) expressed on the axon surface. NRG binding to ErbB2/3 receptors on the Schwann cell surface initiates signaling cascades necessary for myelination. We identify cofilin1, an actin depolymerizing and severing protein, as a downstream target of NRG-ErbB2/3 signaling in rat SC. A five minute exposure of SCs to NRG triggers phosphorylation of …