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Full-Text Articles in Molecular Biology

Dictyostelium Discoideum Protein Kinase C-Orthologue Pkca Regulates The Actin Cytoskeleton Through Interaction With Phospholipase D And P21-Activated Kinase, Sean Singh Jun 2020

Dictyostelium Discoideum Protein Kinase C-Orthologue Pkca Regulates The Actin Cytoskeleton Through Interaction With Phospholipase D And P21-Activated Kinase, Sean Singh

All Dissertations, Theses, and Capstone Projects

Proper regulation of the actin cytoskeleton is crucial to many cellular processes. Many of these processes are regulated by extracellular signaling cues, which direct changes in the actin cytoskeleton, resulting in changes to cellular morphology, and directed motility. The social amoeba, Dictyostelium discoideum, is used as a simple model system to study the translation of extracellular signals to the actin cytoskeleton. When starved, these unicellular amoebae undergo a multicellular developmental process characterized by a tightly regulated sequence of signaling events. This results in chemotaxis and formation of a multicellular aggregate, and ultimately cell differentiation and the formation of a fruiting ...


Testing Kalanchoe Laxiflora U6 Promoters For Optimal Sgrna Expression In Tobacco, Marlee E. Jones May 2020

Testing Kalanchoe Laxiflora U6 Promoters For Optimal Sgrna Expression In Tobacco, Marlee E. Jones

Honors Thesis

Within studies of plant genome modification there is a method of gene alteration which involves using CRISPR/Cas systems in order to target specific gene loci and implement the intended modification. This process is driven by the ability of a single guide RNA (sgRNA) to find this target location within the plant’s genome. This sgRNA strand is expressed due to the presence of a proper RNA promoter. In an effort to understand the effect of an endogenous RNA promoter’s sequence on the successful expression of a sgRNA strand, an experiment was developed involving twelve U6 promoter sequences from ...


The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh May 2020

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products ...


The Effects Of Insulin-Like Growth Factor-1 (Igf-1) And Insulin-Like Growth Factor Receptor (Igfr) Regulation On Cognition And Structure Of Astrocytes, Sariya Khan May 2020

The Effects Of Insulin-Like Growth Factor-1 (Igf-1) And Insulin-Like Growth Factor Receptor (Igfr) Regulation On Cognition And Structure Of Astrocytes, Sariya Khan

Honors Theses

Insulin-like growth factor-1 (IGF-1) is a neuroendocrine signaling hormone that plays an integral role in bone and tissue growth and development. Inhibition of this hormone is known to disrupt the chemistry of the brain, resulting in cognitive impairments such as those seen in many common neurodegenerative diseases. While much research has been conducted on neurons and their relation with IGF-1, the role of astrocytes still needs to be explored. Our research investigates how astrocytes are affected as a result of IGF-1 regulation. Preliminary studies in our laboratory established a connection between IGF-1 and glial fibrillary acidic protein (GFAP), and in ...


Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr May 2020

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits ...


The Effects Of Largazole, A Histone Deacetylase Inhibitor, On Breast Cancer Cell Viability And Metastasis, Hannah Mccowan May 2020

The Effects Of Largazole, A Histone Deacetylase Inhibitor, On Breast Cancer Cell Viability And Metastasis, Hannah Mccowan

Honors Theses

Histone deacetylase enzymes modify epigenetic characteristics of a genome by removing acetyl groups from histone proteins in chromatin. Histone deacetylase inhibitors work by stopping this activity which can have various results in a cell including apoptosis, cell cycle arrest, differentiation, and migration. The purpose of these experiments was to see how largazole, a histone deacetylase inhibitor, affected cell viability for breast cancer and associated metastatic cell lines in both normoxic and hypoxic conditions. The experiment was completed by setting up two 96-well plates with varying concentrations of largazole and conducting a sulforhodamine viability assay. The specific cell lines used in ...


Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko May 2020

Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF ...


Cloning And Expression Of Hydra Innexin 2, A Gap Junction Protein Required For Coordinated Contraction Of The Body Column, Ashley O'Brien May 2020

Cloning And Expression Of Hydra Innexin 2, A Gap Junction Protein Required For Coordinated Contraction Of The Body Column, Ashley O'Brien

Biology Theses

In invertebrates gap junctions are formed by the innexin family of proteins. Remarkably, the genome of Hydra magnipapillata contains 17 innexin genes. This study focused on Hydra innexin-2 (h-Inx2) which is expressed in nerve cells and plays a role in contraction of the body column. The gene sequence of H-Inx2 was obtained from the National Center for Biotechnology Information (NCBI), the gene was synthesized externally and transferred to a vector suitable for expression in Xenopus oocytes (pcDNA3.1 CT-GFP TOPO). The TOPO CT-GFP vector includes a priming site for RNA polymerase which allows in vitro preparation of RNA. Another advantage ...


Crosstalk Between Rho-Family Gtpases At The Division Site During Cytokinesis, Emma Nicole Koory May 2020

Crosstalk Between Rho-Family Gtpases At The Division Site During Cytokinesis, Emma Nicole Koory

Chancellor’s Honors Program Projects

No abstract provided.


Characterization Of Tmx Transmembrane Protein In Bacillus Subtilis And Its Effects On Antibiotic Resistance, Membrane Permeability, And Membrane Fluidity, Henna Zaver May 2020

Characterization Of Tmx Transmembrane Protein In Bacillus Subtilis And Its Effects On Antibiotic Resistance, Membrane Permeability, And Membrane Fluidity, Henna Zaver

Chancellor’s Honors Program Projects

No abstract provided.


A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham May 2020

A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham

Undergraduate Honors Theses

Understanding the genes and mechanisms that regulate the highly important process of neurogenesis in the developing nervous system is crucial to uncovering why disease arises when this system is disrupted. Neural progenitor cells and their multipotent nature allow for the growth of a large pool of stem cells in the early stages of development, but the signal that leads these cells to the irreversible fate of becoming a neuron is unclear. The gene matr3 has been implicated in having a role in the maintenance of undifferentiated neural stem cells but its role needs further investigation to fully reveal how its ...


A Broadly Distributed, Novel Class Of Diiron Enzymes Involved In Para-Aminobenzoate Synthesis, Joseph M. Zambelas Apr 2020

A Broadly Distributed, Novel Class Of Diiron Enzymes Involved In Para-Aminobenzoate Synthesis, Joseph M. Zambelas

Senior Theses

The overall structure and ligand arrangement of diiron enzymes influence their function and catalytic potential, allowing for them to catalyze an expansive breadth of high energy transformations. The diiron enzyme CADD from Chlamydia trachomatis is involved in a novel biosynthetic pathway for p-aminobenzoic acid (pABA), a precursor for tetrahydrofolate. The unique ligand structure and reactivity of CADD and homolog NE1434 provide an intriguing means to contrast structure function relationships with other known diiron enzymes that activate dioxygen. In this work, studies of CADD and NE1434 orthologs and comparison to other diiron enzymes reveal several sequence motifs that are likely critical ...


Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao Mar 2020

Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao

Doctoral Dissertations

Protein-based therapeutics have emerged as a key driver of rapid growth in drug development pipelines. However, developing such protein drugs is not straightforward in most cases, the existence of physiological barriers greatly restricts the efficient delivery of many therapeutic molecules, and therefore limits their clinical applications. A promising way to address this challenge takes advantage of certain transport protein which can effectively across and enhance the permeability of these barriers, such as transferrin (Tf) which can be internalized by malignant cells and cross physiological barriers via transferrin receptor (TfR)-mediated endocytosis and transcytosis. However, developing such products is impossible without ...


Practical Applications And Future Directions Of Genetic Code Expansion: Validation Of Novel Akt1 Substrates And The Design Of A Synthetic Auxotroph Strain Of B. Subtilis, Mcshane M. Mckenna Mar 2020

Practical Applications And Future Directions Of Genetic Code Expansion: Validation Of Novel Akt1 Substrates And The Design Of A Synthetic Auxotroph Strain Of B. Subtilis, Mcshane M. Mckenna

Electronic Thesis and Dissertation Repository

In Chapter 1, site-specifically phosphorylated variants of the oncogene Akt1 were made in Escherichia coli using the orthogonal translation system that enable genetic code expansion with phosphoserine. The differentially phosphorylated variants of Akt1 were used to validate newly predicted Akt1 substrates. The predicted target sites of the peptide substrates were synthesized and subjected to in vitro kinase assays to quantify the activity of each Akt1 phosphorylated variant towards the predicted peptide. A previously uncharacterized kinase-substrate interaction between Akt1 and a peptide derived from RAB11 Family Interacting Protein 2 (RAB11FIP2) was validated in vitro. Chapter 2 describes the preliminary development of ...


Natural Polymorphism Of Mycobacterium Tuberculosis And Cd8 T Cell Immunity, Rujapak Sutiwisesak Feb 2020

Natural Polymorphism Of Mycobacterium Tuberculosis And Cd8 T Cell Immunity, Rujapak Sutiwisesak

GSBS Dissertations and Theses

Coevolution between Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, and the human host has been documented for thousands of years. Interestingly, while T cell immunity is crucial for host protection and survival, T cell antigens are the most conserved region of the Mtb genome. Hypothetically, Mtb adapts under immune pressure to exploit T cell responses for its benefit from inflammation and tissue destruction for ultimately transmission.

EsxH, a gene encoding immunodominant TB10.4 protein, however, contains polymorphic regions corresponding to T cell epitopes. Here, I present two complementary analyses to examine how Mtb modulates TB10.4 for immune evasion ...


Synthesis, Characterization, And Biological Activity Of Imidazolium Salts, David Weader Jan 2020

Synthesis, Characterization, And Biological Activity Of Imidazolium Salts, David Weader

Williams Honors College, Honors Research Projects

Nonmuscle invasive bladder cancer (NMIBC) inflicts thousands of Americans annually, and is typically treated with the immunotherapy BCG. However, due to a BCG shortage, there is a new need for novel treatments of NMIBC. Addressing this issue, several imidazolium salt derivatives were synthesized and characterized with the intent of treatment within the bladder. These imidazolium salts were tested against different human bladder cancer cell lines in vitro to determine their reactivity and cytotoxicity. Among these results are GI50 concentrations for each drug, which is the concentration of drug needed to see growth inhibition in 50% of treated cells. Previous published ...


Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara Jan 2020

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization ...


Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque Jan 2020

Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque

Honors Theses

Non-Celiac Gluten Intolerance (NCGI) has evaded biological and chemical mechanisms since it was first reported in 1978. Celiac Disease, a multi-system immune mediated disorder has long served as the most similar counterpart to NCGI. Less cases of celiac disease are going undiagnosed reflecting an improvement on sensitive and decisive diagnostic tools. However, NCGI has been significantly growing as a diagnosis over the past decade with little match or similarity to the markers found in celiac disease patients. Critical evaluation of NCGI theories, experimentation, and existing hypotheses is necessary. This review seeks to synthesize multiple disciplines of gluten research and enhance ...


Application Of Β-Chloroenals: One-Pot Syntheses To Create Highly Variable, Functional, And Biologically Interesting Molecules, Julia Powell Siewert Jan 2020

Application Of Β-Chloroenals: One-Pot Syntheses To Create Highly Variable, Functional, And Biologically Interesting Molecules, Julia Powell Siewert

Honors Theses

Pyrroles and pyrazoles are privileged structures which provide a molecular framework found in many different classes of bioactive compounds, thus rendering their syntheses useful in pharmaceutical drug development. Additionally, being able to selectively create these molecules with interesting substituents allows for different pharmacological and biological activities, such as antitumor and antibiotic effects. Our group has used β-chloroenals in the application of many different unique synthetic strategies in the past, and here I show that chloroenals can be used to synthesize novel 1,2,5 trisubstituted pyrroles as well as 1,5 di- and 1,4,5 trisubstituted pyrazoles in fewer ...


The Effects Of Signaling Molecules To Agrobacterium Tumefaciens Tumorigenesis At Plant Wound Sites, Nicole Walker Jan 2020

The Effects Of Signaling Molecules To Agrobacterium Tumefaciens Tumorigenesis At Plant Wound Sites, Nicole Walker

Honors Theses

Agrobacterium tumefaciens can live independently within soil before infecting its host (McCullen and Binns, 2006). The bacterium infects the plant through the rhizosphere, an area of soil along the plant root surface which contains microorganisms, making up the “external metabolome” (Bais et al. 2006). As these bacteria live in the rhizosphere, they are exposed to a multitude of chemical signals. These chemical signals include several conditions that must be met before the virulence machinery is expressed. These conditions include signaling from phenols and sugars as well as low PO4 levels and low pH. Upon wounding, sugars and phenols are released ...


The Role Of Reactive Oxygen Species In The Gut Immune Response Of Cat Fleas (Ctenocephalides Felis), Clark Hall Jan 2020

The Role Of Reactive Oxygen Species In The Gut Immune Response Of Cat Fleas (Ctenocephalides Felis), Clark Hall

University Honors Program Theses

Fleas transmit numerous deadly and debilitating diseases, including the causative agents of murine typhus and plague. Because initial entry of these infectious agents occurs while blood feeding, the immune response in the flea gut is considered to be the first line of defense against invading microbes. However, relatively few studies have identified the flea immune molecules that effectively resist or limit infection in the gut. In other hematophagous insects, an immediate immune response to imbibed pathogens is the generation of reactive oxygen species (ROS). In this study, we utilized cat fleas (Ctenocephalides felis) to investigate whether natural infections with bacteria ...


Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh Jan 2020

Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh

Dissertations, Master's Theses and Master's Reports

Insulin is an essential hormone produced by β-cells in the pancreas. The release of insulin is tightly regulated in healthy people in order to control blood sugar level in our body. However, people with Type 2 Diabetes have insufficient insulin secretion from pancreatic β-cells, leaving to high blood sugar (hyperglycemia) and β-cell failure. microRNAs (miRNAs or miR) are newly discovered small regulatory molecules and have emerged as important regulator of cell growth, differentiation, and organ function. Altered miRNA function has been implicated in the pathogenesis of a variety of human disease, including diabetes. In this report, we focus on dissecting ...


“C1orf150”: A Novel Regulator Of Jak2 Kinase, And Candidate Tumor Suppressor In Human Blood Cell Progenitors, Tyler M. Wade Jan 2020

“C1orf150”: A Novel Regulator Of Jak2 Kinase, And Candidate Tumor Suppressor In Human Blood Cell Progenitors, Tyler M. Wade

Honors Theses and Capstones

Erythropoietin (EPO) is an essential growth factor for red blood cell (RBC) production. In response to anemia, hypoxia-sensing cells in the kidney express and release EPO. EPO then acts in bone marrow to drive RBC formation from erythroid progenitors. Upon binding to its cell surface receptor, EPO triggers a JAK2 kinase signaling cascade for progenitor cell growth. Our lab has discovered a novel regulator of JAK2, “C1ORF150” (“150”). “150” is conserved in H sapiens and primates and is a new orthologue of the B-cell receptor adaptor protein and tumor marker, HGAL. Using a shRNA knockdown approach, I investigated the actions ...


The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd Jan 2020

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry ...


Role Of Ciliary Proteins Adp Ribosylation Factor Like Gtpase 13b (Arl13b) And Bardet-Biedl Syndrome-8 (Bbs8) In Photoreceptor Outer Segment Morphogenesis, Maintenance, And Viability, Tanya L. Dilan Jan 2020

Role Of Ciliary Proteins Adp Ribosylation Factor Like Gtpase 13b (Arl13b) And Bardet-Biedl Syndrome-8 (Bbs8) In Photoreceptor Outer Segment Morphogenesis, Maintenance, And Viability, Tanya L. Dilan

Graduate Theses, Dissertations, and Problem Reports

Photoreceptor neurons are modified primary cilia with an extended ciliary compartment known as the outer segment (OS). The mechanisms behind the elaboration of photoreceptor cilia, OS morphogenesis, and maintenance remain poorly understood. In this work, we focused on dissecting the role of two ciliary proteins, the small GTPase ADP-ribosylation factor-like GTPase 13B (ARL13B) and Bardet-Biedl Syndrome-8 (BBS8) in the context of photoreceptor biology. Both BBS8 and ARL13B are linked to defects in ciliogenesis (cilia development) and Retinitis Pigmentosa (vision loss). ARL13B is implicated in regulating ciliary length, and BBS8 is part of the Bardet-Biedl Syndrome complex (BBSome); the BBSome is ...


The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine Jan 2020

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute ...


Characterization Of The Influences Of Human Cytomegalovirus Glycoprotein O (Go) Expression On Gh/Gl Complexes Assembly And Its Polymorphisms On Cell-Free And Cell-To-Cell Spread, And Antibody Neutralization., Le Z. Day Jan 2020

Characterization Of The Influences Of Human Cytomegalovirus Glycoprotein O (Go) Expression On Gh/Gl Complexes Assembly And Its Polymorphisms On Cell-Free And Cell-To-Cell Spread, And Antibody Neutralization., Le Z. Day

Graduate Student Theses, Dissertations, & Professional Papers

Human cytomegalovirus (HCMV) is widely spread throughout the world and immunocompromised individuals can suffer severe diseases from HCMV infection. Once the infection is established, HCMV can spread through the body and infect many major somatic cell types. The glycoproteins H and L (gH/gL) on HCMV envelope can be bound by either gO or the UL128-131 proteins to form complexes gH/gL/gO and gH/gL/UL128-131 that are critical for viral entry and spread, and these two complexes are important targets of neutralizing antibodies. Strains of HCMV vary considerably in the levels of gH/gL/gO and gH/gL ...


Peroxiredoxin 6 And Inflammation In Alzheimer's Disease, Jared Ferrell-Penniman Dec 2019

Peroxiredoxin 6 And Inflammation In Alzheimer's Disease, Jared Ferrell-Penniman

Biological Sciences Theses and Dissertations

Alzheimer’s disease (AD) is known for its debilitating symptoms and poor prognosis. However, despite intense research into neurodegenerative diseases, there are few therapies targeted at the underlying mechanisms of the disease. Oxidative stress (OS) and inflammation are cellular phenomena thought to be key to the progression of the disease. Critically, peroxiredoxin 6 (Prx6), an antioxidant protein with multiple functions, has been identified from mammalian studies as a potential regulator of both OS and inflammation that may have a specific effect on AD. This project seeks to elucidate the role of Prx6 in AD as well as the underlying mechanisms ...


Modulating Mcm Levels Causes Differential Loading At Origins Of Replication And Changes Replication Timing, Livio Dukaj Dec 2019

Modulating Mcm Levels Causes Differential Loading At Origins Of Replication And Changes Replication Timing, Livio Dukaj

GSBS Dissertations and Theses

DNA replication is a highly complex part of cell metabolism that ensures safe propagation of the genome through tight regulation of the expression, localization, and activity of a large number of factors. Replication starts from distinct sites in the genome and initiation events are temporally ordered in a manner that is, on average, highly reproducible across cell populations. The specific order with which different parts of the genome are replicated has been proposed to be important to processes such as gene expression, cell differentiation, development, and genome evolution. Nevertheless, the fundamental mechanisms that are responsible for establishing these timing programs ...


Elucidating Enhancer Function In Epidermal Development And Filaggrin Loss-Of-Function Variants In African American Atopic Dermatitis, Mary Elizabeth Mathyer Dec 2019

Elucidating Enhancer Function In Epidermal Development And Filaggrin Loss-Of-Function Variants In African American Atopic Dermatitis, Mary Elizabeth Mathyer

Arts & Sciences Electronic Theses and Dissertations

The epidermis is the outermost tissue of the skin and provides the body’s first line of defense against external assaults. The epidermis is primarily composed of keratinocytes that terminally differentiate and rise apically toward the surface to form the semipermeable barrier of the skin. A hallmark of keratinocyte terminal differentiation is the expression of genes from the Epidermal Differentiation Complex (EDC) locus. Many of the EDC protein products contribute to the structural integrity of the skin barrier, evidenced by several gene knockouts such as loricrin, and even genetic variation within gene coding sequences, that modulate the integrity of the ...