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Full-Text Articles in Medicine and Health Sciences
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. …
Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah
Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah
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Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …
Role Of Gsk3 In The Immunopathogenesis Of Eae, Amber Rowse
Role Of Gsk3 In The Immunopathogenesis Of Eae, Amber Rowse
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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 …
Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo
Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo
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CD4 T cells are central to the organization of the immune response through the secretion of cytokines that recruit and activate other immune cells. Following infection and pathogen control, the majority of the effector CD4 T cells undergo apoptosis, leaving a subset that persists and gives rise to the memory T cell pool. Upon encountering the same pathogen, memory CD4 T cells respond rapidly, providing enhanced protection from re-infection. What determines which effector CD4 T cells will survive is unclear; however, there are a number of factors both intrinsic to the cell as well as external signals from the environment …
The Role Of Il-21 And Il-17 In Regulating Follicular T Helper Cells In Germinal Center Response Of Autoimmunity, Yanna Ding
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Overreactivity of the germinal center (GC) is a central feature of autoantibody-mediated autoimmune diseases. Follicular T helper (Tfh) cells are the primary T helper subset that migrates to the incipient GC and forms close contacts with GC-B cells to promote GC formation and help GC-B cell differentiation, resulting in high-affinity antibody production. Increased levels of interleukin (IL)-21 and aberrant accumulation or function of Tfh cells have been associated with autoimmune disease severity in humans and lupus-prone mice. Follicular regulatory T (Tfr) cells are the regulatory T cell subset that also localizes in the GC and inhibits GC B cell differentiation. …
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 …
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 …
Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf
Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf
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Environmental exposures such as diet, use of antibiotics, and lifestyle have significant impact on the health of an individual. One mechanism that acts as a major pathway in these environmental exposures is the role intestinal commensal microbiota play in both metabolic and immunological responses. Metabolic pathways are altered through changes in metabolites provided by commensal microbiota; alterations in microbial make-up can have drastic impacts on metabolic function. Similarly, the development and maturation of the immune system is dependent on the intestinal microbes to induce tolerance and act as both an immune modulator as well as a barrier against pathogens. We …
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 …
Adap1 And Arf6 Mediate Regulated Secretory Trafficing In Neurosecretory Cells And Neurons, Sharday Ewell
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 …
Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson
Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson
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Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …
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
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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 …
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 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
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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 …
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 …
The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek
The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek
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The human immune system must be able to adapt to a wide spectrum of invading pathogens in order to keep the human body alive. This variation includes directed recombination and mutation at the level of the individual and genetic variation and natural selection at the population level. A direct consequence of the adaptability of the immune system is autoimmunity: as the immune system adapts to a shifting spectrum of antigens, it can shift to self-antigens, and therefore attack the body and cause disease. Since genetic factors are part of this adaptability, they are also connected with autoimmune disease. SLE is …
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 …
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
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Depressed serum immunoglobulin levels and recurrent sinopulmonary infections mark Common Variable Immune Deficiency (CVID). Many family members of CVID patients also suffer Recurrent Sino-Pulmonary Infection (RESPI) but have normal serum immunoglobulins. We identified HLAB44 positive identical female twins who suffer sinopulmonary infections and are discordant for CVID and RESPI. Flow cytometry subsets showed equivalent numbers of immature B cells (BC) in both twins, but lower numbers of transitional and mature BC in the CVID twin. Presented is an in-depth comparison of V (D) J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between µ H chain repertoires …
The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor
The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor
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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
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 …
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
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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 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, …
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
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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 Endothelial Mannose Residues In Monocyte Adhesion Under Flow, David Wayne Scott
Role Of Endothelial Mannose Residues In Monocyte Adhesion Under Flow, David Wayne Scott
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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 …
Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs
Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs
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ABSTRACT Multiple Myeloma (MM) remains the second most common hematologic malig-nancy occurring in adults, which primarily affects the skeletal system causing severe bone destruction, spinal cord compression and hypercalcemia. Current therapies, which include chemotherapy, radiotherapy, autologouos stem cell transplantation and in some cases surgery, have extended the median survival between 3 and 10 years. However, MM is still incurable and therefore improving current therapies or developing newer ones to reduce the burden of osteolytic damage and extend survival rate will be highly beneficial for patient management. The long-term goal of this study is to develop a novel therapeutic approach to …
Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li
Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li
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Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …
The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu
The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu
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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. …
The Impact Of Transcription And Nucleoid-Associated Proteins On Dna Supercoiling In Escherichia Coli And Salmonella Typhimurium, Andrews Agbleke
The Impact Of Transcription And Nucleoid-Associated Proteins On Dna Supercoiling In Escherichia Coli And Salmonella Typhimurium, Andrews Agbleke
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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 …