Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 56 for “"Hypermutation"”.
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Mechanism of Mismatch Repair Induced Mutagenesis in Somatic Hypermutation
… of a humoral immune response. However, somatic hypermutation of the rearranged V region in the immunoglobulin locus generates new antibody affinities, accompanied by the selection of B cells that produce superior antibody affinities. Somatic hypermutation is initiated by the conversion of G:C …
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Hypermutation and adaptation of experimentally evolved marine Vibrio bacteria
… of the evolved strains revealed unprecedented hypermutation in three of nine parallel lineages. These mutator lines arose independently, and each of them accumulated more than 1500 single-base mutations. By comparison, there are only 302 single-base differences between the ancestor strain and …
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Implications of Dysregulated Antibody Hypermutation Patterns in Multiple Sclerosis Patients
… We previously discovered a pattern of somatic hypermutation in the antibody genes expressed isolated from cerebrospinal fluid (CSF) B cells of patients with MS and those at high risk for developing MS. The focus of this thesis project was to further characterize this pattern of mutation termed …
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Lethal Hypermutation Induced by the Innate Cellular Restriction Factor APOBEC Destroys HIV-1 in Infected Humanized Mice
… enzymatic activity of APOBEC3G and 3F to induce hypermutation of the HIV-1 genome. These observations make the Vif/APOBEC axis a tantalizing therapeutic target. The ability of APOBEC to restrict HIV in vivo however remains to be addressed. The adaptive capability of HIV allows the virus to …
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A novel genomics and bioinformatics approach to assess immunoglobulin and T cell receptor rearrangements and somatic hypermutation in lymphoproliferative disorders
… affinity maturation for diversification. Somatic hypermutation (SHM) is a B cell specific affinity maturation process whereby point mutations are intentionally inserted into the genomic sequence to marginally alter the confirmation of immunoglobulin (Ig) receptors. SHM is part of normal B cell …
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The Evolution of Glioblastoma: A Single Case Study
… typical of TMZ treatment. The fact that the hypermutation did not appear until the second recurrence raises questions about the mechanism of hypermutation. The therapeutic apoptotic action of TMZ relies on the function of the mismatch repair (MMR) pathway. In the second recurrence we observed …
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Interactions Between APOBEC3 and Murine Retroviruses: Mechanisms of Restriction and Drug Resistance
… an active source of viral restriction leading to hypermutation of viral DNA synthesized during reverse transcription. These mutations can result in viral lethality via disruption of critical genes, but in some cases is insufficient to completely obstruct viral replication. This sublethal level of …
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Selection Dynamics in the Germinal Center During Antibody Affinity Maturation
… iterative rounds of migration between a zone of hypermutation and proliferation (the dark zone, or DZ) and a zone of selection (the light zone, or LZ). The mechanism whereby somatic antibody mutants are selected on the basis of affinity has been elusive. In the first part of this thesis, I …
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INTERACTIONS BETWEEN THE GLYCOSYLATED GAG PROTEIN OF A MURINE LEUKEMIA VIRUS AND MURINE APOBEC3: NOVEL INSIGHTS INTO HOW A MURINE LEUKEMIA VIRUS COUNTERACTS A RESTRICTION FACTOR
… single-stranded DNA which ultimately results in hypermutation of newly synthesized proviral DNA. Other deaminase-independent mechanisms of inhibition have been identified, such as directly inhibiting reverse transcription. Both HIV and murine leukemia viruses (MuLVs) have evolved mechanisms to …
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INTERACTIONS BETWEEN THE GLYCOSYLATED GAG PROTEIN OF A MURINE LEUKEMIA VIRUS AND MURINE APOBEC3: NOVEL INSIGHTS INTO HOW A MURINE LEUKEMIA VIRUS COUNTERACTS A RESTRICTION FACTOR
… single-stranded DNA which ultimately results in hypermutation of newly synthesized proviral DNA. Other deaminase-independent mechanisms of inhibition have been identified, such as directly inhibiting reverse transcription. Both HIV and murine leukemia viruses (MuLVs) have evolved mechanisms to …
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Studies of Replication Repair Deficient Brain Tumorigenesis Using Mouse Modeling
… RRD brain tumors are characterized by universal hypermutation, resistance to standard chemoradiation, and variable susceptibility to immune-based therapies. Despite their clinical relevance, representative immunocompetent models of recently defined RRD subgroups are lacking. These subgroups are …
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Development and road-testing of an inducible hypermutator strain of Pseudomonas aeruginosa
Hypermutation occurs when the mismatch repair (MMR) system becomes defective due to e.g., mutation. In Pseudomonas aeruginosa (PA), the mutS gene is commonly mutated in hypermutator strains. MutS mutants display an elevated mutation rate (>100-fold, compared with the wild-type (WT)) and are often …
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The evolution of the autoantibody response in Graves’ disease
… B cell clone which diversified through somatic hypermutation. The shared germline genes were expressed as recombinant (r) Fab germline and did not display measurable binding to TSHR in three assay systems: radioreceptor assay, flow cytometry and cAMP stimulation bioassay. Hence the precursor B …
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Germline mutation in rare disease
… to try and identify a genetic cause for this hypermutation. For two of the individuals, I found rare homozygous paternal variants that fell into two different DNA repair genes and are the likely cause. I also explore whether variants in DNA repair genes more generally impact germline mutation …
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Isolation and engineering of a high affinity antibody against P-selectin glycoprotein ligand-1 (PSGL-1)
… strategies exploited by B cells such as somatic hypermutation, receptor revision (... CDR replacement), receptor editing (chain shuffling), and amino acid insertions and deletions. Together with yeast surface display and flow cytometric screening (FACS), this approach has been used to effect at …
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STEPWISE DIFFERENTIATION OF IL21-PRODUCING FOLLICULAR HELPER T CELLS REVEALS DISTINCT DEVELOPMENTAL AND FUNCTIONAL STATES
… center formation, maintenance and somatic hypermutation at distinct stages of the germinal center response to a SARS-CoV-2 protein vaccine. Together, these studies demonstrate the transitionary stages of Tfh development and how control of progression through these stages regulates germinal …
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Regulation of Immunoglobulin Gene Diversification By Noncoding RNA's
… the genetic code. B lymphocytes perform somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin locus to generate an antibody repertoire diverse in both affinity and function. These somatic diversification processes are catalyzed by activation-induced cytidine …
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Role of AID and microRNA-155 in c-myc-IgH Translocations
… mature B cells undergoing AID dependent somatic hypermutation (SHM), duplications or deletions that would necessitate a double strand break make up 6% of all the Ig V-JH region associated somatic mutations. Furthermore, DNA breaks can be detected at this locus in B cells undergoing SHM. To …
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HIV Specific B Cell Response in Patients With Broadly Neutralizing Serum Activity
… binding site were isolated. Despite extensive hypermutation, these broadly neutralizing CD4bs antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. Thus, the IgG memory B cell compartment in the selected group of patients with …
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