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Articles 1 - 11 of 11
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Combining Footprinting Mass Spectrometry And Molecular Dynamics Simulation For Structural Studies In Membrane Proteins, Fengbo Zhou
Arts & Sciences Electronic Theses and Dissertations
Membrane proteins are essential in many cellular processes and represent ~60% of all current drug targets. Due to technical limits, membrane proteins of various types were not studied extensively in the past and the biochemistry and functionality of them remain unclear. The structural biology methodologies require pure isolated protein samples for us to resolve their structure and study their biochemical functions. For such in vitro studies, however, membrane proteins often become unstable when isolated from their native lipid bilayer environment. To overcome the challenge, I employed a novel methodology of solubilizing membrane proteins in solution without detergent. I reconstituted ferroportin, …
Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger
Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger
Arts & Sciences Electronic Theses and Dissertations
Behavior in higher eukaryotes is a complex process which integrates signals in the environment, the genetic makeup of the organism, and connectivity in the nervous system to produce extremely diverse adaptations to the phenomenon of existence. Unraveling the subcellular components that contribute to behavioral output is important for both understanding how behavior occurs in an unperturbed state, as well as understanding how behavior changes when the underlying systems that generate it are altered. Of the numerous molecular species that make up a cell, the regulation of messenger RNAs (mRNAs), the coding template of all proteins, is of key importance to …
The Role Of Membrane Excitability In Insulin Regulation, Christopher Howard Emfinger
The Role Of Membrane Excitability In Insulin Regulation, Christopher Howard Emfinger
Arts & Sciences Electronic Theses and Dissertations
In mammals, ATP-sensitive K+ (KATP) channels are essential regulators of insulin secretion from pancreatic islet [beta]-cells, illustrated by the finding that gain-of-function mutations in KATP channels (KATP-GOF) cause neonatal diabetes mellitus (NDM). However, variability in symptom severity and effectiveness of treatment is seen in NDM, even for those with the same mutation and in the same family. Short-term treatment of mice expressing KATP-GOF mutations in [beta]-cells (KATP-GOF mice) with the KATP blocker glibenclamide during disease onset results in two outcomes: one subset becomes severely diabetic (non-remitters), whereas the other subset remains below the glucose levels at which significant side effects …
The Role Of Mesenchymal Stromal Cells And Classical Dendritic Cells In The Maintenance And Regulation Of The Bone Marrow Niche, Jingzhu Zhang
The Role Of Mesenchymal Stromal Cells And Classical Dendritic Cells In The Maintenance And Regulation Of The Bone Marrow Niche, Jingzhu Zhang
Arts & Sciences Electronic Theses and Dissertations
The bone marrow niche is an important microenvironment for the regulation of normal and malignant hematopoiesis. The first discovered niche component is mesenchymal stromal cells, which are the major source for the production and secretion of multiple niche factors. Mesenchymal stromal cells are heterogeneous and various transgenes have been used to target non-identical but overlapping subpopulations. To further characterize the heterogeneity of mesenchymal stromal cells, we tested the targeting specificity of three tissue-specific Cre-recombinase transgenes. We show that in addition to osteoblasts, Ocn-Cre targets a majority of Cxcl12-abundant reticular (CAR) cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset …
Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones, Cynthia Holland
Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones, Cynthia Holland
Arts & Sciences Electronic Theses and Dissertations
Unlike humans and other metazoans, organisms such as fungi, bacteria, and plants have retained the enzymatic machinery necessary to synthesize their aromatic amino acids de novo. Chorismate, the final product of the shikimate pathway, is the precursor to the three aromatic amino acidsѠtryptophan, tyrosine, and phenylalanineѠand is upstream of a number of plant growth hormones, including auxins and benzoates. Phenylalanine and tyrosine both stem from the precursor prephenate, which is formed from chorismate by chorismate mutase, and use dehydrogenases, aminotransferases, and dehydratases in their biosynthetic pathways. Although aromatic amino acid biosynthesis is important for protein synthesis, secondary metabolism, and human …
The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action, Nicholas Kevork Goldner
The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action, Nicholas Kevork Goldner
Arts & Sciences Electronic Theses and Dissertations
Daptomycin, a last line-of-defense antibiotic for treating Gram-positive infections, is experiencing clinical failure against important infectious agents, including Corynebacterium striatum. The recent transition of daptomycin to generic antibiotic status is projected to dramatically increase availability, use, and clinical failure. Despite daptomycinճ more than 30-year history as an important antibiotic, four major questions were left unanswered. 1) How do bacteria become hyper-resistant to daptomycin? 2) What is the in vivo membrane target of daptomycin? 3) How does daptomycin interact with the membrane? 4) What is daptomycinճ mechanism of killing? These four questions have plagued the daptomycin field, and even now conflicting …
Building On Nature: Spectroscopic Studies Of Photosynthesis-Inspired Pigments, Fused Light Harvesting Proteins, And Bacterial Reaction Center Mutants, Kaitlyn Faries
Arts & Sciences Electronic Theses and Dissertations
Photosynthesis is the dominant form of solar energy conversion on the planet, making it critical to understand the fundamentals of the process in order to effectively mimic and improve upon it for human energy needs. The initial stages of photosynthesis include light harvesting and chemical conversion of that harvested energy via electron transport, with both of these stages relying on pigments (or chromophores) such as chlorophyll and specific protein architectures for the processes. In this work, the fundamental underpinnings of photosynthetic light harvesting and electron transport are explored via spectroscopy of various photosynthetic systems with altered natural pigments and proteins. …
Development Of Lc-Ms For The Identification And Characterization Of Non-Adjacent Dna Photoproduct Formation In G-Quadruplex Forming Sequences, Claudia Posadas
Development Of Lc-Ms For The Identification And Characterization Of Non-Adjacent Dna Photoproduct Formation In G-Quadruplex Forming Sequences, Claudia Posadas
Arts & Sciences Electronic Theses and Dissertations
Ultraviolet light is well known to induce cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts in duplex DNA, which interfere with DNA replication and transcription. Recently, a new class of DNA photoproducts known as anti cyclobutanepyrimidine dimers have been discovered, which form in G-quadruplex forming sequences in solution. G-quadruplex structures have been proposed to form in human DNA telomeres and certain promoters in vivo but evidence for their existence has been lacking. Since anti-cyclobutante pyrimidine dimers have been shown to form in G-quadruplex forming sequences, their formation in irradiated human cells could be used to confirm the existence …
Effect Of Dna Sequence Context, Dna Structure, And Excitation Method On Cyclobutane Pyrimidine Dimer Formation, Chen Lu
Arts & Sciences Electronic Theses and Dissertations
The cis-syn cyclobutane pyrimdine dimer (CPD) is the major photoproduct resulting from UV irradiation of duplex DNA that results in C to T mutations found in human skin. CPDs with the anti stereochemistry were recently discovered to be formed in human telomeric DNA that adopts a quadruplex structure in vitro and may also play a role in the effects of sunlight in vivo. In this thesis, the effect of telomeric DNA structure on the formation of the anti-CPDs is investigated, as well as the effect of sequence context on cis-syn CPD formation which could help explain the origin of DNA …
Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari
Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari
Arts & Sciences Electronic Theses and Dissertations
Gene regulation involves the integration of different sources of information at multiple levels. The action of transcription factors is integrated at cis-regulatory sequences (CRSs). Information from many CRSs is combined to drive spatiotemporally regulated gene expression. Prediction of CRS activity from DNA sequence is challenging because most occurrences of transcription factor binding sites (TFBS) are not functional. I assayed the activity of thousands of genomic sequences with Activator Protein 1 (AP-1) binding sites in K562 cells to identify features in flanking sequences that distinguish functional from non-functional TFBS. I find that sequence features directly adjacent to the AP-1 core motif, …
Novel Approaches To Studying The Effects Of Cis-Regulatory Variants In The Central Nervous System, Susan Shen
Novel Approaches To Studying The Effects Of Cis-Regulatory Variants In The Central Nervous System, Susan Shen
Arts & Sciences Electronic Theses and Dissertations
For decades, studies of the genetic basis of disease have focused on rare coding mutations that disrupt protein function, leading to the identification of hundreds of genes underlying Mendelian diseases. However, many complex diseases are non-Mendelian, and less than 2% of the genome is coding. It is now clear that non-coding variants contribute to disease susceptibility, but the precise underlying mechanisms are generally unknown. Cis-regulatory elements (CREs) are transcription factor (TF)-bound genomic regions that regulate gene expression, and variants within CREs can therefore modify gene expression. The putative locations of CREs in a variety of cell types have been identified …