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Full-Text Articles in Life Sciences
Transcription, Editing, And Switching Of Antibody Genes, Rafael Casellas
Transcription, Editing, And Switching Of Antibody Genes, Rafael Casellas
Student Theses and Dissertations
B lymphocytes are the antibody producing cells of the immune system. During B cell lymphopoiesis in the bone marrow, immunoglobulin molecules are assembled from V, D, and J gene segments through a process known as V(D)J recombination. Because of its stochastic nature, V(D)J recombination is expected to create self-reactive specificities. In targeted animals carrying autoantibodies, these specificities were shown to be silenced by deletion, anergy, and receptor editing. While anergy and deletion physically eliminate the autoreactive clone, receptor editing salvages it by replacing its immunoglobulin receptor through ongoing V(D)J recombination. Once a functional non-self -reactive receptor is generated, B lymphocytes …
Targeting Receptor-Histidine Kinase Signaling In Staphylococcus Aureus, Gholson J. Lyon
Targeting Receptor-Histidine Kinase Signaling In Staphylococcus Aureus, Gholson J. Lyon
Student Theses and Dissertations
Two-component signaling systems involving receptor-histidine kinases (RHKs) are present in all branches of life outside of the animal kingdom. Remarkably, very little is known concerning the extracellular ligands that presumably bind to R H K s to initiate signaling. The two-component agr signaling circuit in the bacterial pathogen, Staphylococcus aureus, is one system where the ligands are known in chemical detail. These ligands (the AIPs) are short (7-9 aminoacyl residue) peptides containing a thiolactone structure, in which the oc-carboxyl group of the C-terminal amino acid is linked to the sulfhydryl group of a cysteine, which is always the fifth amino …
Zipro1: Fine Tuning Proliferation In Discrete Cell Populations, Christopher Wynder
Zipro1: Fine Tuning Proliferation In Discrete Cell Populations, Christopher Wynder
Student Theses and Dissertations
Zipro 1 a zinc finger transcnption factor that has a restricted pattern of expression in several tissues. The main cells expressing Ziprol are proliferating cells from epidermal lineages. This includes the cerebellar granule cells (GCs), nasal epithelia and dermal papilla. Through gene dosage experiments we have shown that Ziprol is involved in proliferation GCs, Hair follicles and the Cranio-facial process. Overexpression of Ziprol results an increase in the number of G C s , this increase in G C s directly regulates the appearance of secondary fissure in the cerebellum. Overexpression also results in follicular dysplasia caused by an increase …
Structural Studies Of Dna Replication Proteins By X-Ray Crystallography And Molecular Dynamics, Yanxiang Zhao
Structural Studies Of Dna Replication Proteins By X-Ray Crystallography And Molecular Dynamics, Yanxiang Zhao
Student Theses and Dissertations
Organisms that span evolutionary space utilize an assembly of proteins (the replicase) in a coordinated effort to faithfully replicate their genomes. This chromosomal replicase consists of three functionally distinct subassemblies. The first of these is the polymerase/exonuclease complex, which harbors DNA synthesis and proofreading activities. The second functional complex is the sliding clamp which adopts a ring-shaped structure, composed of either two or three protomers. It confers processivity onto the polymerase subunit by tethering it to the template. The third complex is the clamp loader complex, which loads the sliding clamp onto DNA using energy from ATP binding and hydrolysis. …
Stress And Hippocampal Plasticity, Kara Pham
Stress And Hippocampal Plasticity, Kara Pham
Student Theses and Dissertations
The addition of new neurons continues in the dentate gyrus of the adult rat, and this process has been previously shown to be regulated by adrenal steroid hormones, Nmethyl- D-aspartate (NMDA) receptor activity, psychosocial stress and learning and memory. Repeated restraint stress is known to induce neuroanatomical changes in the hippocampus, such as dendritic remodeling in CA3 neurons and mossy fiber terminal rearrangement, and these alterations are reversible, suggesting that the hippocampal system experiences a certain degree of plasticity in response to stress. This dissertation examines the effects of chronic restraint stress on several parameters of hippocampal plasticity, including dentate …
Leptin And The Control Of Body Weight And Metabolism: Role For Stearoyl Coa Desaturase-1 And Other Leptin-Regulated Genes In The Liver, Paul Cohen
Student Theses and Dissertations
Leptin is an adipocyte-derived hormone that regulates energy balance, metabolism, and the neuroendocrine response to altered nutrition. Mice lacking leptin (ob/ob) or its receptor (db/db) are massively obese and hyperphagic. They also have increased triglyceride deposits in multiple peripheral organs, including the liver, massively enlarged and steatotic. Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. This response is characterized by weight loss, depletion of lipid from peripheral tissues, and enhanced insulin sensitivity. The mechanisms underlying these actions were largely unknown. This thesis addressed leptin's metabolic effects on the liver, an organ with a critical …
Nova Regulation Of Alternative Splicing In The Cns, B Kate Dredge
Nova Regulation Of Alternative Splicing In The Cns, B Kate Dredge
Student Theses and Dissertations
Nova-1, an autoantigen in paraneoplastic opsoclonus myoclonus ataxia (POMA), a disorder associated with gynecologic cancer and CNS motor dysfunction, is a neuronspecific nuclear RNA binding protein. The work presented here confirms that Nova-1 acts as a regulator of alternative splicing in vivo. In addition to the known target Nova-dependent splicing regulation, exon 3A of glycine receptor a2 subunit (GlyRa2), two new targets are identified, which are the alternative exon, E9 in the inhibitory neurotransmitter receptor subunit, GABAARy2, and the alternatively spliced exon H in Nova-l's own message. Nova acts to enhance alternative exon inclusion in GlyRcc2 and GABAARy2 mRNAs and …
Mapping Genes For Complex Traits: Obesity, Diabetes, Hypertension, And Dyslipidemia On The Pacific Island Of Kosrae, Dvora Shmulewitz
Mapping Genes For Complex Traits: Obesity, Diabetes, Hypertension, And Dyslipidemia On The Pacific Island Of Kosrae, Dvora Shmulewitz
Student Theses and Dissertations
One of the current challenges in human genetics is to map genes for common, complex diseases. For powerful mapping of such phenotypes, the suggestions are to analyze the underlying quantitative traits with covariate corrections in large extended pedigrees with multipoint analysis. This is virtually impossible to do with the current linkage programs, due to the computation difficulties of exactly calculating every possibility. Instead, sampling methods that sample the most likely data configuration from all the possibilities need to be used. This has been implemented in the reversible jump Markov chain Monte Carlo method Loki, which can carry out segregation and …
Site-Specific Incorporation Of Biochemical And Biophysical Probes Into Proteins Using Expressed Protein Ligation, Mande Holford
Site-Specific Incorporation Of Biochemical And Biophysical Probes Into Proteins Using Expressed Protein Ligation, Mande Holford
Student Theses and Dissertations
Protein engineering can be made far more powerful if a protein is not only expressed recombinantly but also altered covalently using synthetic chemistry. These two methods are brought together in the protein semi-synthesis technique Expressed Protein Ligation (EPL). In EPL, recombinant and synthetic polypeptides are joined together via a chemoselective ligation reaction. EPL was originally used to attach synthetic constructs to the C-terminus of recombinant proteins, but is now used to attach recombinant or synthetic polypeptides either at the N- or C-terminus of a protein or into the core of a protein. This thesis illustrates, with three distinct applications, the …
Biogenesis And Traffic Of The Potassium Channel, Natalie De Souza
Biogenesis And Traffic Of The Potassium Channel, Natalie De Souza
Student Theses and Dissertations
Excitability of nerve and muscle cells depends on the number and the types of ion channels expressed at the plasma membrane. This work examines aspects of biogenesis and traffic of the Shaker voltage-gated potassium channel. Shaker is an oligomeric, polytopic membrane protein and, as such, its biogenesis begins at the endoplasmic reticulum (ER). I have studied (i) targeting of Shaker to the ER and stable integration into the lipid bilayer, (ii) N-linked glycosylation, assembly and folding Shaker in the ER, and (iii) export of Shaker from the ER and subsequent traffic to the surface. Targeting to the endoplasmic reticulum, integration …