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Full-Text Articles in Medicine and Health Sciences
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
All ETDs from UAB
The mesolimbic dopamine (DA) pathway, which consists of dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), is heavily implicated in drug addiction. Exposure to drugs of abuse results in increases in extracellular concentrations of DA in the NAc, which in turn activates an immediate early gene (IEG) expression program that primarily consists of activity-dependent transcription factors, such as the AP1 subunits Fos and JunB. IEGs engage a set of temporally and functionally distinct genes, termed the late response gene (LRG) expression program. While gene expression changes are critical for drug-dependent adaptations, two major …
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
All ETDs from UAB
Exposure to drugs of abuse alters transcriptional programs and neuronal activity, leading to long-lasting cellular and behavioral adaptations that may contribute to addiction. The nucleus accumbens (NAc), part of the mesocorticolimbic dopamine pathway, plays a central role in motivation, reward, and reward-related learning, and this brain region is highly implicated in the development and maintenance of addiction. However, the specific contributions of defined cell populations in the NAc to drug reward processes is still poorly understood. Here, we used electrophysiological, optogenetic, and single-nucleus RNA-sequencing (snRNA-seq) approaches in a rodent model system to define the acute physiological and transcriptional responses of …
Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke
Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke
All ETDs from UAB
Drug addiction is a chronic relapsing condition inflicting tremendous harm to individuals and society with ineffective treatment options available to most people. Drugs of abuse elevate dopamine levels in a brain region known as the nucleus accumbens (NAc), and activate gene programs considered essential for producing lasting synaptic and cell state changes which underlie the generation of addictive behavior. These gene expression changes remain poorly understood due to a complex heterogenous cellular architecture, and the rapidly fluctuating nature of the transcriptional processes themselves which make investigation difficult. Recent technical advances increase access to both profiling and manipulating these transcriptional changes …
Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull
Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull
All ETDs from UAB
My graduate research has focused on understanding the elongation kinetics of RNA polymerase I (Pol I), the enzyme responsible for synthesizing ribosomal RNA (rRNA), and defining how inhibition of ribosome biogenesis may be used as a cancer therapeutic strategy. Here, I have defined key biophysical features of Pol I and I have expanded the field’s understanding of Pol I elongation by: 1) characterizing the enzymatic properties of Pol I by mutational analysis of the polymerase itself, and by 2) elucidating the role of DNA sequence on Pol I arrest and nucleolytic cleavage activity. In recent years, Pol I has become …
Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell
Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell
All ETDs from UAB
Drugs of abuse increase dopamine concentrations in the nucleus accumbens, a key reward structure that integrates contextual and cue-related information and regulates motivated behavior. This surge of dopamine triggers cell signaling cascades that converge in the nucleus to cause changes in gene expression, which are thought to lead to the observed functional and structural alterations in the reward circuit after exposure to drugs of abuse. However, while various drugs of abuse cause transcriptional changes, previously available tools have not had the capacity to deeply characterize these gene programs. Therefore, we optimized a dual lentivirus CRISPR system for targeted gene modulation …
The Effects Of The Initially Transcribed Sequence On Reiterative Transcription In Escherichia Coli, Jeffery Michael Vahrenkamp
The Effects Of The Initially Transcribed Sequence On Reiterative Transcription In Escherichia Coli, Jeffery Michael Vahrenkamp
All ETDs from UAB
Transcription, the synthesis of a ribonucleic acid transcript using a nucleic acid template, is the first step in gene expression for all life. In most organisms, high fidelity transcription is achieved through the formation of an RNA:DNA hybrid which allows the RNA polymerase to maintain the correct register. Slippage, which would lead to improper base pairing, is prevented by the heterogeneous sequence of the DNA template. However, when homogenous tracts of bases are present in the template, slippage can occur, allowing a single base in the template to encode multiple bases in the transcript in a process called reiterative transcription. …
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
All ETDs from UAB
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 …
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 …
Transcriptional Regulation Of Gfap, Sujeong Yeo
Transcriptional Regulation Of Gfap, Sujeong Yeo
All ETDs from UAB
Glial fibrillary acidic protein (GFAP) is an astrocytic intermediate filament protein whose levels are increased in response to CNS injuries. Aim one of my thesis is to find the regulatory elements of the GFAP promoter responsible for its expression properties using a transgenic approach, since previous studies showed inconsistent results between in vitro and in vivo approaches. Two contiguous DNA segments previously implicated in transcriptional control of the GFAP gene, the B region (bp -1612 to -1489), and the C1.1 and C1.2 regions (bp -1488 to -1399), were analyzed. Block mutation of each of 4 contiguous sequences together spanning the …
Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker
Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker
All ETDs from UAB
The bacterial chromosome is dynamic. The principle goal of my research is to understand how DNA topology is altered by transcription in Salmonella enterica serovar Typhimurium LT2. Gamma delta-resolution requires two direct repeat Res sites to pair a plectonemic synapse. Previous work from our lab showed that the zones of high transcription inhibited gamma delta-resolution. Using phage λ recombineering methods, we have developed Salmonella strains to study ribosomal RNA operons, which are the most highly transcribed genes in bacteria. We propose a molecular model for how supercoiling generated by high levels of transcription modifies chromosome structure.
Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn
Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn
All ETDs from UAB
Calreticulin (CRT), classically known for its chaperone functions in the endoplasmic reticulum and as a calcium regulator, also is found on the cell surface and in the extracellular matrix. It is involved in many cellular processes including signaling, adhesion, migration, apoptotic cell clearance, gene regulation, and production of a fibronectin matrix. CRT has been suggested to play a role in wound healing and fibrosis. Therefore, these studies investigated the role of CRT in collagen production, an important extracellular matrix molecule in wounding and fibrosis. We demonstrated that CRT regulates collagen through transcription, secretion, and processing. We also investigated the role …