The Regulation Of Notch Signaling By Src Kinase And Polyphenolic Compounds,
2018
Boise State University
The Regulation Of Notch Signaling By Src Kinase And Polyphenolic Compounds, Bryce David Lafoya
Boise State University Theses and Dissertations
Cellular signaling pathways provide cells with the means to sense their environment and communicate with other cells. The Notch signaling pathway is comprised of a set of protein machines which work in unison to coordinate cellular processes in response to stimuli coming from neighboring cells and changing microenvironmental conditions. Notch signaling is an important mode of cellular communication which is crucial to many processes involved in development and disease. During Notch activation, information about the extracellular environment is fed into the cell and relayed to the nucleus through a number of biochemical processes. The information-rich messages carried by Notch signaling …
Canonical Nuclear Factor-Κb Signaling In Satellite Stem Cell Homeostasis And Function.,
2018
University of Louisville
Canonical Nuclear Factor-Κb Signaling In Satellite Stem Cell Homeostasis And Function., Alex R. Straughn
Electronic Theses and Dissertations
Satellite cells are adult stem cells that are required for the regeneration of skeletal muscle following injury. However, the signaling mechanisms that regulate satellite stem cell homeostasis and function in adult animals remain less understood. Nuclear factor-kappa B (NF-kB) is a major nuclear transcription factor that regulates the gene expression of a plethora of molecules involved in cellular proliferation, differentiation, survival, and the inflammatory immune response. NF-kB can be activated through a canonical or non-canonical pathway. However, the role of canonical NF-kB signaling in the regulation of satellite stem cell function during skeletal muscle regeneration has not been yet investigated …
Identifying The Molecular Functions Of The C-Terminal Region Of The Human Proteins,
2018
University of Nevada, Las Vegas
Identifying The Molecular Functions Of The C-Terminal Region Of The Human Proteins, Surbhi Sharma
UNLV Theses, Dissertations, Professional Papers, and Capstones
The Carboxyl (C-) terminus of proteins is usually disordered and flexible allowing proteins to engage in an induced-fit type of interactions with other molecules. Often, these interactions are mediated through the C- terminal minimotifs, which are peptide sequences of 2-15 contiguous residues found in a protein with a known molecular function. These functions include protein binding, trafficking, and post-translational modifications. In this dissertation, we investigated how many human proteins contain the C-terminal minimotifs. We cataloged 3,593 previously verified C-terminal minimotifs representing 17% of the human proteome. Based on these observations, we asked: Does the remaining 83% of the human proteome …
The Role Of Rad4 In Dna Repair And Its Interplay With Telomeres In Tetrahymena Thermophila,
2018
Missouri State University
The Role Of Rad4 In Dna Repair And Its Interplay With Telomeres In Tetrahymena Thermophila, Emily Nischwitz
Graduate Theses/Dissertations
Telomeres are repetitive parts of the genome that act as a protective end cap to the chromosomes. Telomeres are critical to the integrity and stability of the genome, therefore, ensuring that their sequence is maintained, even after damage, is crucial. Much of the pioneering work responsible for explaining telomeres has been conducted in ciliates, specifically in Tetrahymena thermophila. Telomeres in T. thermophila have a high amount of tandem thymine repeats (GGGGTT) and, thus, are susceptible to ultraviolet light (UV) induced lesions called pyrimidine dimers, which must be repaired by nucleotide excision repair (NER). In humans, Xeroderma Pigmentosum C (XPC) …
Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer.,
2018
Keck Graduate Institute, KGI
Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez
KGI Theses and Dissertations
Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in …
Pias-Family Proteins Negatively Regulate Glis3 Transactivation Function Through Sumo Modification In Pancreatic Β Cells,
2018
Murray State University
Pias-Family Proteins Negatively Regulate Glis3 Transactivation Function Through Sumo Modification In Pancreatic Β Cells, Tyler M. Hoard, Xiaoping Yang, Anton M. Jetten, Gary T. Zeruth Dr.
Faculty & Staff Research and Creative Activity
Gli-similar 3 (Glis3) is Krüppel-like transcription factor associated with the transcriptional regulation of insulin. Mutations within the Glis3 locus have been implicated in a number of pathologies including diabetes mellitus and hypothyroidism. Despite its clinical significance, little is known about the proteins and posttranslational modifications that regulate Glis3 transcriptional activity. In this report, we demonstrate that the SUMO-pathway associated proteins, PIASy and Ubc9 are capable of regulating Glis3 transactivation function through a SUMO-dependent mechanism. We present evidence that SUMOylation of Glis3 by PIAS-family proteins occurs at two conserved lysine residues within the Glis3 N-terminus and modification of Glis3 by SUMO …
Water Pharmacophore: Designing Ligands Using Molecular Dynamics Simulations With Water,
2018
Korea University
Water Pharmacophore: Designing Ligands Using Molecular Dynamics Simulations With Water, Sang Won Jung, Minsup Kim, Steven Ramsey, Tom Kurtzman, Art E. Cho
Publications and Research
In this study, we demonstrate a method to construct a water-based pharmacophore model which can be utilized in the absence of known ligands. This method utilizes waters found in the binding pocket, sampled through molecular dynamics. Screening of compound databases against this water-based pharmacophore model reveals that this approach can successfully identify known binders to a target protein. The method was tested by enrichment studies of 7 therapeutically important targets and compared favourably to screening-by-docking with Glide. Our results suggest that even without experimentally known binders, pharmacophore models can be generated using molecular dynamics with waters and used for virtual …
Transcriptomics Of Learning,
2018
University of Missouri, St. Louis
Transcriptomics Of Learning, Pablo Iturralde
Theses
Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …
Identification Of Novel Δnp63Α-Regulated Mirnas Using An Optimized Small Rna-Seq Analysis Pipeline,
2018
Wright State University - Main Campus
Identification Of Novel Δnp63Α-Regulated Mirnas Using An Optimized Small Rna-Seq Analysis Pipeline, Suraj Sakaram, Michael P. Craig, Natasha T. Hill, Amjad Aljiagthmi, Christian Garrido, Oleg Paliy, Michael Bottomley, Michael L. Raymer, Madhavi Kadakia
Biochemistry and Molecular Biology Faculty Publications
Advances in high-throughput sequencing have enabled profiling of microRNAs (miRNAs), however, a consensus pipeline for sequencing of small RNAs has not been established. We built and optimized an analysis pipeline using Partek Flow, circumventing the need for analyzing data via scripting languages. Our analysis assessed the effect of alignment reference, normalization method, and statistical model choice on biological data. The pipeline was evaluated using sequencing data from HaCaT cells transfected with either a non-silencing control or siRNA against ΔNp63α, a p53 family member protein which is highly expressed in non-melanoma skin cancer and shown to regulate a number of miRNAs. …
Anemarrhena Asphodeloides Bunge And Its Constituent Timosaponin‐Aiii Induce Cell Cycle Arrest And Apoptosis In Pancreatic Cancer Cells,
2018
University of South Florida
Anemarrhena Asphodeloides Bunge And Its Constituent Timosaponin‐Aiii Induce Cell Cycle Arrest And Apoptosis In Pancreatic Cancer Cells, Catherine B. Marelia, Arielle Sharp, Tiffany A. Shemwell, Y. C. Zhang, Brant R. Burkhardt
Molecular Biosciences Faculty Publications
Pancreatic cancer is one of the most recalcitrant and lethal of all cancers. We examined the effects of Anemarrhena asphodeloides (AA) and timosaponin‐AIII (TAIII), a steroidal saponin present in AA, on pancreatic cancer cell proliferation and aimed to elucidate their potential apoptotic mechanisms of action. Viability assays and cell cycle analysis revealed that both AA and TAIII significantly inhibited pancreatic cancer cell proliferation and cell cycle progression compared to treatment with gemcitabine, the standard chemotherapeutic agent for advanced pancreatic cancer. We identified a dose‐dependent increase in caspase‐dependent apoptosis and activation of pro‐apoptotic PI3K/Akt pathway proteins, with a subsequent downregulation of …
Characterizing The Recognition Motif And Novel Substrates Of Carm1,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Characterizing The Recognition Motif And Novel Substrates Of Carm1, Sitaram Gayatri
Dissertations and Theses (Open Access)
A limited pool of proteins attains vast functional repertoire due to posttranslational modifications (PTMs). Arginine methylation is a common posttranslational modification, which is catalyzed by a family of nine protein arginine methyltransferases or PRMTs. These enzymes deposit one or two methyl groups to the nitrogen atoms of arginine side-chains. Elucidating the substrate specificity of each PRMT will promote a better understanding of which signaling networks these enzymes contribute to. Although many PRMT substrates have been identified, and their methylation sites mapped, the optimal target motif for each of the nine PRMTs has not been systematically addressed. Here we describe the …
Zika Modulates Arthropod Histone Methylation In Mosquito Cells,
2018
Old Dominion University
Zika Modulates Arthropod Histone Methylation In Mosquito Cells, Telvin Lee Harrell
Biological Sciences Theses & Dissertations
Epigenetics is the heritable series of covalent modifications that affect chromatin structure, gene expression, and protein function. Methylation is one such epigenetic modification that involves the addition of chemical modifying entities, such as methyl groups, on nucleic acids or proteins. Recent studies have reported that Zika virus (ZIKV) modulates methylation of human and viral RNA important for its replication in vertebrate cells. However, little is known whether ZIKV exerts methylation in arthropod vectors. In this study, I show that ZIKV modulates S-adenosyl methionine (SAMe) synthase, an enzyme involved in the production of SAMe, and histone methylation for its survival in …
Exploring The Role Of Rna Polymerase Iii Complex Assembly On Ribosomal Dna Silencing In Saccharomyces Cerevisiae,
2018
Louisiana State University and Agricultural and Mechanical College
Exploring The Role Of Rna Polymerase Iii Complex Assembly On Ribosomal Dna Silencing In Saccharomyces Cerevisiae, Kyle Thomas Kern
LSU Doctoral Dissertations
The yeast rDNA region is host to a number of transcriptional regulatory elements, which work in conjunction to generate essential RNA subunits of ribosomes, as well as protecting the region from DNA damage. The role of RNA polymerase III complex binding at the 5S gene on rDNA silencing in the NTS2 region was investigated, both by use of a TY1:MET15 reporter insert and a MET15 gene integration at an endogenous SphI site. It was discovered that Pol III complexes do have an effect on reporter expression in the NTS2 region, though the specific effect was different based on the method …
Snf1 Cooperates With The Cwi Mapk Pathway To Mediate The Degradation Of Med13 Following Oxidative Stress,
2018
Rowan University
Snf1 Cooperates With The Cwi Mapk Pathway To Mediate The Degradation Of Med13 Following Oxidative Stress, Stephen D Willis, David C Stieg, Kai Li Ong, Ravina Shah, Alexandra K. Strich, Julianne H Grose, Katrina F Cooper
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Eukaryotic cells, when faced with unfavorable environmental conditions, mount either pro-survival or pro-death programs. The conserved cyclin C-Cdk8 kinase plays a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core Mediator complex of RNA polymerase II. In Saccharomyces cerevisiae, oxidative stress triggers Med13 destruction, which releases cyclin C into the cytoplasm to promote mitochondrial fission and programmed cell death. The SCFGrr1 ubiquitin ligase mediates Med13 degradation dependent on the cell wall integrity pathway, MAPK Slt2. Here we show that the AMP kinase Snf1 activates a second …
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees,
2018
University of Texas at El Paso
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins
Selected Works Temporary Series
This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees,
2018
University of Texas at El Paso
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins
Departmental Papers (Biology)
This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …
A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer,
2018
University of South Florida
A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi
USF Tampa Graduate Theses and Dissertations
Lung cancer is the second most common cancer type and is associated with high mortality rates. The survival rate for lung cancer patients has increased slowly in the last decade mainly as the result of the development of novel targeted and immune therapies. However, non-small cell lung cancer patients lacking known or actionable driver mutations and small cell lung cancer patients with recurrent disease are still in urgent need of new therapies. Drug repurposing is an efficient way to identify new therapies since it uses clinically relevant small molecule drugs. Determination of off-targets of small molecules is a novel approach …
Codon Usage Revisited: Lack Of Correlation Between Codon Usage And The Number Of Trna Genes In Enterobacteria,
2018
Universidad de Chile
Codon Usage Revisited: Lack Of Correlation Between Codon Usage And The Number Of Trna Genes In Enterobacteria, Joaquín Rojas, Gabriel Castillo, Lorenzo Eugenio Leiva, Sara Elgamal, Omar Orellana, Michael Ibba, Assaf Katz
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
It is widely believed that if a high number of genes are found for any tRNA in a rapidly replicating bacteria, then the cytoplasmic levels of that tRNA will be high and an open reading frame containing a higher frequency of the complementary codon will be translated faster. This idea is based on correlations between the number of tRNA genes, tRNA concentration and the frequency of codon usage observed in a limited number of strains as well as from the fact that artificially changing the number of tRNA genes alters translation efficiency and consequently the amount of properly folded protein …
Mathematical Modeling Of Nutrient Signaling And Growth In Saccharomyces Cerevisiae,
2018
Virginia Polytechnic Institute and State University
Mathematical Modeling Of Nutrient Signaling And Growth In Saccharomyces Cerevisiae, Amogh P. Jalihal, Pavel Kraikivski, T.M. Murali, John J. Tyson
Biology and Medicine Through Mathematics Conference
No abstract provided.
Acetic Acid Induces Sch9p-Dependent Translocation Of Isc1p From The Endoplasmic Reticulum Into Mitochondria,
2018
Universidade do Minho (Portugal)
Acetic Acid Induces Sch9p-Dependent Translocation Of Isc1p From The Endoplasmic Reticulum Into Mitochondria, António Rego, Katrina F Cooper, Justin Snider, Yusuf A Hannun, Vítor Costa, Manuela Côrte-Real, Susana R Chaves
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Changes in sphingolipid metabolism have been linked to modulation of cell fate in both yeast and mammalian cells. We previously assessed the role of sphingolipids in cell death regulation using a well characterized yeast model of acetic acid-induced regulated cell death, finding that Isc1p, inositol phosphosphingolipid phospholipase C, plays a pro-death role in this process. Indeed, isc1∆ mutants exhibited a higher resistance to acetic acid associated with reduced mitochondrial alterations. Here, we show that Isc1p is regulated by Sch9p under acetic acid stress, since both single and double mutants lacking Isc1p or/and Sch9p have the same resistant phenotype, and SCH9 …
