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Full-Text Articles in Medicine and Health Sciences
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 …
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 …
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
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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 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. …
Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi
Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi
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Basal-like breast cancers (BLBC) display aggressive clinical behavior attributed to the presence of cancer stem cells (CSCs). TRA-8, a monoclonal antibody that binds specifically to TRAIL death receptor 5, preferentially induces apoptosis in BLBC subtype cells; however it is unknown if TRA-8 is also cytotoxic to the CSC population. Moreover, some BLBC cell lines are resistant to TRA-8, and overcoming resistance is critical for clinical translation of this therapy. One potential approach to overcome TRA- 8 resistance is to target the Wnt/ß-catenin pathway. LRP6 is a cell surface receptor that is an indispensable element of the Wnt/ß-catenin signaling pathway that …
The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall
The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall
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The ubiquitin proteasome system (UPS) plays a critical role in regulating a diversity of cellular processes that are essential to neuronal function, such as synaptic transmission, axon guidance, and neurite outgrowth. Dysfunctions of the UPS are linked with many neurodegenerative disorders, including motor neuron diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), although it is not known how UPS dysfunction contributes to disease pathology. The proteasome, an approximate 2.5 megadalton protein complex comprised of a 20S core particle and 19S regulatory particle, is the site of ubiquitin-mediated proteolysis in the cell. Recent studies have linked ubiquitin specific …
Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy
Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy
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The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine …
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 …
New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor
New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor
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Hedgehog (Hh) signaling is required for many developmental processes, and causes several diseases and cancers. Described in chapter one below, vertebrate Hh sig-naling is dependent on the primary cilium (PC), a small organelle that extends from the surface of most mammalian cell types. A better understanding of how the PC modulates Hh signaling is important, as defects in the structure or function of PC result in severe human disorders termed the ciliopathies. For example, patients with Meckel-Gruber Syndrome have extra digits and neural tube defects, which are Hh both related pheno-types. In chapter two we sought to further understand the …
Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston
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
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 …
Structure-Function Analysis Of Tyrosyl-Dna Phosphodiesterase I, Evan Comeaux
Structure-Function Analysis Of Tyrosyl-Dna Phosphodiesterase I, Evan Comeaux
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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 …
Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney
Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney
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Pneumococcal conjugate vaccines (PCVs) containing subsets of the >90 capsular polysaccharide antigens have been successful as a means of decreasing invasive and non-invasive pneumococcal disease worldwide. However, this success is limited to the specif-ic capsular serotypes against which PCVs are formulated and studies have reported the increase of nonvaccine serotypes. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media and was released without efficacy data. In this study we set out to 1) determine potential efficacy for invasive and noninvasive pneumococcal disease and 2) …
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 …
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. …
The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos
The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos
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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
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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 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 Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh
All ETDs from UAB
Multiple Sclerosis (MS) is an autoimmune disease resulting from aberrant immune cells causing demyelination. We utilize the well-studied mouse model, experimental autoimmune encephalomyelitis (EAE), to decipher the underlying pathogenesis of MS. Effector CD4 T-cells play a critical role during EAE because the disease is induced by adoptively transferring myelin-specific CD4 T-cells into naïve mice. Classically, effector CD4 T-cells have been divided into distinct subsets based on their functional properties: Th1 cells produce IFNγ, Th2 cells secrete IL-4, IL-5, and IL-13, Th17 cells make IL-17A, IL-17F, IL-21, and IL-22, and regulatory T cells produce IL-10. Th1 cells were originally identified as …
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 …
Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James
Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James
All ETDs from UAB
The principle objective of this dissertation is to develop a thorough understanding of the genetics and biochemistry of capsule synthesis. Specifically, it involves the identification and characterization of the capsular glycosyltransferases in Streptococcus pneumoniae serotype 2, with investigations into their regulation. S. pneumoniae (the pneumococcus) is a significant human pathogen that has the ability to persist as a commensal and then transition to a virulent state, the latter of which is a major contributor to global morbidity and mortality. The capsular polysaccharide (CPS) of S. pneumoniae is a protective surface structure that plays an integral role in this disease process. …
Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe
Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe
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Glioblastoma multiforme (GBM) is the most common and deadly primary brain malignancy necessitating improved understanding of GBM biology. In this study, we explore the role of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) in the context of GBM. We have discovered that the MARCKS protein regulates GBM growth as well as response to radiation therapy through its effects on proliferation, senescence, and DNA repair based on our studies in cell culture and in patient-derived xenograft tumors implanted in mice. Importantly, our analysis of clinical patient data demonstrates that MARCKS is an independent predictor for outcome in GBM patients. Indeed, high MARCKS …
The Molecular Mechanisms Underlying Cardiac Hypertrophy Due To Volume Overload., Justin Andrew Barnes
The Molecular Mechanisms Underlying Cardiac Hypertrophy Due To Volume Overload., Justin Andrew Barnes
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Mitral regurgitation (MR) is a common form of heart disease, but there are no approved medical therapies for MR or other cardiovascular conditions associated with hemodynamic volume overload (VO) and eccentric remodeling. We have previously shown that a standard heart failure treatment, ß-adrenergic system blockade (ß-RB), improves function in animal models of VO and in MR patients without attenuating the adverse eccentric hypertrophy that occurs in conjunction with VO. This paradox highlights how poorly we understand eccentric remodeling of the heart, and a better understanding of the molecular mechanisms at work in VO must be obtained before we can develop …
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
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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 …
Tgf-Ss And Erg In Intervertebral Disc Development, Megan Karen Cox
Tgf-Ss And Erg In Intervertebral Disc Development, Megan Karen Cox
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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 …
Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig
Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig
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SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the …
An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas
An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas
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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
Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner
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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 …
Characterization Of The Mumps Virus Replicase, Robert Marsden Cox
Characterization Of The Mumps Virus Replicase, Robert Marsden Cox
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Negative strand RNA viruses (NSV) are unique because their nucleocapsids are used directly as the template for both transcription and replication. The viral genomic RNA is coated by the nucleoprotein (N) for the entirety of the NSV replication cycle. The viral polymerase, which is composed of the L and P proteins, can only recognize encapsidated RNA as the template for RNA synthesis. Our previous studies have solved the EM structure of the MuV N-RNA complex at 25Å . This structure revealed how the nucleocapsid is assembled and provides an initial model for examining how the viral polymerase may recognize the …