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Articles 1 - 30 of 4647

Full-Text Articles in Life Sciences

Long-Term Therapeutic Efficacy Of Intravenous Aav-Mediated Hamartin Replacement In Mouse Model Of Tuberous Sclerosis Type 1, Shilpa Prabhakar, Pike See Cheah, Xuan Zhang, Max Zinter, Maria Gianatasio, Eloise Hudry, Roderick T. Bronson, David J. Kwiatkowski, Anat Stemmer-Rachamimov, Casey A. Maguire, Miguel Sena-Esteves, Bakhos A. Tannous, Xandra O. Breakefield Dec 2019

Long-Term Therapeutic Efficacy Of Intravenous Aav-Mediated Hamartin Replacement In Mouse Model Of Tuberous Sclerosis Type 1, Shilpa Prabhakar, Pike See Cheah, Xuan Zhang, Max Zinter, Maria Gianatasio, Eloise Hudry, Roderick T. Bronson, David J. Kwiatkowski, Anat Stemmer-Rachamimov, Casey A. Maguire, Miguel Sena-Esteves, Bakhos A. Tannous, Xandra O. Breakefield

Open Access Articles

Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome caused by mutations in TSC1 or TSC2, encoding hamartin and tuberin, respectively. These proteins act as a complex that inhibits mammalian target of rapamycin (mTOR)-mediated cell growth and proliferation. Loss of either protein leads to overgrowth in many organs, including subependymal nodules, subependymal giant cell astrocytomas, and cortical tubers in the human brain. Neurological manifestations in TSC include intellectual disability, autism, hydrocephalus, and epilepsy. In a stochastic mouse model of TSC1 brain lesions, complete loss of Tsc1 is achieved in homozygous Tsc1-floxed mice in a subpopulation of neural cells in ...


Rna Recognition By The Glucocorticoid Receptor Dna-Binding Domain, Nicholas Victor Parsonnet Nov 2019

Rna Recognition By The Glucocorticoid Receptor Dna-Binding Domain, Nicholas Victor Parsonnet

Biochemistry Graduate Theses & Dissertations

Regulation of gene expression by transcription factors (TFs) and their co-regulatory molecules forms much of the basis of how cells interact with their environment. Long noncoding RNAs (lncRNAs) are emerging as a new class of co-regulatory factors, exploiting diverse sequence and structure motifs to interact directly with TFs. An outstanding prototype of this model is glucocorticoid receptor (GR), a TF which binds multiple RNAs in vivo and typifies the molecular decoy model—competitive binding between RNA and DNA at the TF DNA-binding domain. For example, GR binds the noncoding RNA Gas5, a tumor suppressor and growth arrest-specific RNA, via its ...


#3 - Generation Of Sult4a1 Gene Mutations In Sh-Sy5y Cells, Elisabeth Bradberry, Frank Crittenden Nov 2019

#3 - Generation Of Sult4a1 Gene Mutations In Sh-Sy5y Cells, Elisabeth Bradberry, Frank Crittenden

Georgia Undergraduate Research Conference (GURC)

The cytosolic sulfotransferases (SULT) are a superfamily of enzymes that catalyze the metabolism of various substrates throughout the body. One member, SULT4A1, has no known substrates and is highly conserved among all vertebrates which is not a shared characteristic among the SULT family. Also unique among the SULTs, SULT4A1 localizes with mitochondria of neurons. Recent reports have suggested that this protein is believed play a protective role against oxidative stress. The goal of this project was to generate a SH-SY5Y cell line with a SULT4A1 gene deletion using CRISPR gene-editing technology. These neuroblastoma cells were used because of their ease ...


#7 - The Role Of Rnf216/Triad3 In Neuroinflammation Through Interactions With Toll-Like-Receptors, Dustin Grossman Nov 2019

#7 - The Role Of Rnf216/Triad3 In Neuroinflammation Through Interactions With Toll-Like-Receptors, Dustin Grossman

Georgia Undergraduate Research Conference (GURC)

Ubiquitin E3 ligases are enzymes that mark certain substrates with ubiquitin proteins which leads to different cellular fates. Ring finger protein 216 (RNF216) is a ubiquitin E3 ligase that is involved in synaptic plasticity, inhibiting cellular autophagy, and the immune response in the peripheral nervous system. Previous literature has demonstrated that RNF216 participates in various aspects of inflammation by regulating ubiquitination and proteasomal degradation of receptor-interacting serine-threonine kinase 1 (RIPK1), toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), and TIR-domain-containing adapter-inducing interferon-β (TRIF), targeting TNF receptor associated factor 3 (TRAF3) for degradation. TLRs initiate signal transduction pathways which can lead ...


#1 - Alu-Derived Orthologous Chromosome Classification For The Primate Order, Mehul Mehra, Nitish Sood, Anav Mittal, Christopher Bates Nov 2019

#1 - Alu-Derived Orthologous Chromosome Classification For The Primate Order, Mehul Mehra, Nitish Sood, Anav Mittal, Christopher Bates

Georgia Undergraduate Research Conference (GURC)

Orthologous chromosomes between any family of related species have been difficult thus far to obtain, often requiring substantial biochemical testing and computationally-intensive genomic analysis. By employing computational strategies on repeated non-coding DNA, numerous advantages to accurately determining orthologous chromosomes between species can be ascertained. Throughout the primate genome, the Alu repeated element covers 10% of the genome among higher order primates, spanning across each chromosome. These non-protein-coding sequences replicate themselves repeatedly, with each iteration allowed to mutate more than their protein-coding counterparts. Therefore, upon examining the genetic sequences of such “junk” DNA, increasingly specific distinctions can be made between any ...


#11 - Sequence Analysis Of Alu Repeated Elements For Primate Phylogenetic Tree Construction, Nitish Sood, Mehul Mehra, Anav Mittal, Christopher Bates Nov 2019

#11 - Sequence Analysis Of Alu Repeated Elements For Primate Phylogenetic Tree Construction, Nitish Sood, Mehul Mehra, Anav Mittal, Christopher Bates

Georgia Undergraduate Research Conference (GURC)

Phylogenetic tree construction can be a particularly challenging and time-intensive process. This study employs a novel computational approach to phylogenetic tree construction, using the Alu repeating element, a SINE. Repetitive elements including Short and Long Interspersed Nuclear Elements (SINEs/LINEs) have successfully been applied as accurate tools for phylogenetic analysis, as they are predominately unidirectional and homoplasy-free. However, previous analysis of phylogenetic relationships using these repeating elements has been limited to a small number of isolated repeats among relatively few organisms.

As a highly repetitive sequence, the Alu element and its associated subfamilies can provide detailed analysis on evolutionary divergence ...


Discovery Of An Egfr Inhibitor For The Treatment Of Lung And Other Cancers, Jodie Meng '20 Nov 2019

Discovery Of An Egfr Inhibitor For The Treatment Of Lung And Other Cancers, Jodie Meng '20

Student Publications & Research

The Epidermal Growth Factor Receptor (EGFR), a transmembrane protein involved in the regulation of signaling pathways, is frequently overexpressed in epithelial tumors. First generation EGFR TKIs, such as erlotinib and gefitinib, traditionally improved outcomes for non-small-cell lung carcinoma and pancreatic cancer patients by attaching competitively and reversibly to the ATP binding domain of EGFR. Second-generation EGFR TKIs have been developed to combat resistance among patients, despite demonstrating toxic side effects. In the present study, 1400 selective inhibitors were designed based on the molecular scaffolds of first and second generation EGFR TKIs. Results were refined by parameters outlined in Lipinski’s ...


Selaginella Moellendorffii Telomeres: Conserved And Unique Features In An Ancient Land Plant Lineage, Eugene V. Shakirov, Dorothy E. Shippen Oct 2019

Selaginella Moellendorffii Telomeres: Conserved And Unique Features In An Ancient Land Plant Lineage, Eugene V. Shakirov, Dorothy E. Shippen

Yevgeniy (Eugene) Shakirov

Telomeres, the essential terminal regions of linear eukaryotic chromosomes, consist of G-rich DNA repeats bound by a plethora of associated proteins. While the general pathways of telomere maintenance are evolutionarily conserved, individual telomere complex components show remarkable variation between eukaryotic lineages and even within closely related species. The recent genome sequencing of the lycophyte Selaginella moellendorffii and the availability of an ever-increasing number of flowering plant genomes provides a unique opportunity to evaluate the molecular and functional evolution of telomere components from the early evolving non-seed plants to the more developmentally advanced angiosperms. Here we analyzed telomere sequence in S ...


Heterologous Expression Of Pantoea Agglomerans Phytase Gene Optimized For Plant-Host Expression, N. N. Khabipova, L. R. Valeeva, I. B. Chastukhina, M. R. Sharipova, Eugene V. Shakirov Oct 2019

Heterologous Expression Of Pantoea Agglomerans Phytase Gene Optimized For Plant-Host Expression, N. N. Khabipova, L. R. Valeeva, I. B. Chastukhina, M. R. Sharipova, Eugene V. Shakirov

Yevgeniy (Eugene) Shakirov

Here we report expression and characterization of recombinant bacterial phytase PaPhyC from Pantoea sp. Codon-optimized phytase gene was expressed E.coli BL21 pLysS and protein expression was confirmed by Western blotting. Recombinant protein expressed in E.coli has high phytase activity. We show that PaPhyC recombinant phytase has different molecular masses when expressed in bacteria and plants, suggesting that possible protein glycosylation in plants may influence its overall size.


P-20 Characterization Of Cgx Tautomerase And Mutants With Acetylenecarboxylic Acid, Daniel Chi, Karen Draths, Amaya Sirinimal Oct 2019

P-20 Characterization Of Cgx Tautomerase And Mutants With Acetylenecarboxylic Acid, Daniel Chi, Karen Draths, Amaya Sirinimal

Celebration of Research and Creative Scholarship

In the production of commodity chemicals through microbial synthesis, the use of renewable sugars as a raw material is increasingly common. However, this generates competition between its use in the chemical industry and the food industry. Therefore, developing alternative biosynthetic pathways involving other renewable feedstocks to replace starch-derived feedstocks is crucial. CgX, a tautomerase native to Corynebacterium glutamicum, catalyzes the hydration and subsequent decarboxylation of acetylenecarboxylic acid (ACA), a compound that can be produced from methane gas and carbon dioxide, both abundant greenhouse gases. The products formed from the CgX (wild-type)-catalyzed reaction of ACA results in a mixture of ...


Genetic Rescue Of Fragile X Syndrome Links Fmrp Deficiency To Codon Optimality-Dependent Rna Destabilization, Huan Shu, Elisa Donnard, Botao Liu, Joel D. Richter Oct 2019

Genetic Rescue Of Fragile X Syndrome Links Fmrp Deficiency To Codon Optimality-Dependent Rna Destabilization, Huan Shu, Elisa Donnard, Botao Liu, Joel D. Richter

University of Massachusetts Medical School Faculty Publications

Fragile X syndrome (FXS) is caused by inactivation of FMR1 gene and loss of its encoded product the RNA binding protein FMRP, which generally represses translation of its target transcripts in the brain. In mouse models of FXS (i.e., Fmr1 knockout animals; Fmr1 KO), deletion of Cpeb1, which encodes a translational activator, mitigates nearly all pathophysiologies associated with the disorder. Here we reveal unexpected wide-spread dys-regulation of RNA abundance in Fmr1 KO brain cortex and its rescue to normal levels in Fmr1/Cpeb1 double KO mice. Alteration and restoration of RNA levels are the dominant molecular events that drive ...


Ripk1 Mediates Tnf-Induced Intestinal Crypt Apoptosis During Chronic Nf-Kappab Activation, Jerry Wong, Matija Zelic, John Bertin, Michelle A. Kelliher, Monica Guma Oct 2019

Ripk1 Mediates Tnf-Induced Intestinal Crypt Apoptosis During Chronic Nf-Kappab Activation, Jerry Wong, Matija Zelic, John Bertin, Michelle A. Kelliher, Monica Guma

Open Access Articles

BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a major pathogenic effector and a therapeutic target in inflammatory bowel disease (IBD), yet the basis for TNF-induced intestinal epithelial cell (IEC) death is unknown, because TNF does not kill normal IECs. Here, we investigated how chronic nuclear factor (NF)- kappaB activation, which occurs in human IBD, promotes TNF-dependent IEC death in mice.

METHODS: Human IBD specimens were stained for p65 and cleaved caspase-3. C57BL/6 mice with constitutively active IKKbeta in IEC (Ikkbeta(EE)(IEC)), Ripk1(D138N/D138N) knockin mice, and Ripk3(-/-) mice were injected with TNF or lipopolysaccharide. Enteroids were ...


Highly Structured Homolog Pairing Reflects Functional Organization Of The Drosophila Genome, Jumana Alhaj Abed, Jelena Erceg, Anton Goloborodko, Son C. Nguyen, Ruth B. Mccole, Wren Saylor, Geoffrey Fudenberg, Bryan R. Lajoie, Job Dekker, Leonid A. Mirny, C-Ting Wu Oct 2019

Highly Structured Homolog Pairing Reflects Functional Organization Of The Drosophila Genome, Jumana Alhaj Abed, Jelena Erceg, Anton Goloborodko, Son C. Nguyen, Ruth B. Mccole, Wren Saylor, Geoffrey Fudenberg, Bryan R. Lajoie, Job Dekker, Leonid A. Mirny, C-Ting Wu

Program in Systems Biology Publications and Presentations

Trans-homolog interactions have been studied extensively in Drosophila, where homologs are paired in somatic cells and transvection is prevalent. Nevertheless, the detailed structure of pairing and its functional impact have not been thoroughly investigated. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, showing that homologs pair with varying precision genome-wide, in addition to establishing trans-homolog domains and compartments. We also elucidate the structure of pairing with unprecedented detail, observing significant variation across the genome and revealing at least two forms of pairing: tight pairing, spanning contiguous small domains, and loose pairing, consisting of single ...


Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch Oct 2019

Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch

Open Access Articles

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we use cryoelectron microscopy to determine the capsid structure of thermostable phage P74-26 to 2.8-A resolution. We find P74-26 capsids exhibit an overall architecture very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid ...


Pollen-Derived Rnas Are Found In The Human Circulation, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Anupama Singh, Selim E. Tanriverdi, Olga Vitseva, Daniel Levy, Allison M. Keeler, Marzieh Ezzaty Mirhashemi, Mai K. Elmallah, Mark Gerstein, Joel Rozowsky, Kahraman Tanriverdi, Jane E. Freedman Sep 2019

Pollen-Derived Rnas Are Found In The Human Circulation, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Anupama Singh, Selim E. Tanriverdi, Olga Vitseva, Daniel Levy, Allison M. Keeler, Marzieh Ezzaty Mirhashemi, Mai K. Elmallah, Mark Gerstein, Joel Rozowsky, Kahraman Tanriverdi, Jane E. Freedman

Open Access Articles

The presence of nonhuman RNAs in man has been questioned and it is unclear if food-derived miRNAs cross into the circulation. In a large population study, we found nonhuman miRNAs in plasma by RNA sequencing and validated a small number of pine-pollen miRNAs by RT-qPCR in 2,776 people. The presence of these pine-pollen miRNAs associated with hay fever and not with overt cardiovascular or pulmonary disease. Using in vivo and in vitro models, we found that transmission of pollen-miRNAs into the circulation occurs via pulmonary transfer and this transfer was mediated by platelet-pulmonary vascular cell interactions and platelet pollen-DNA ...


Characterization Of The Role Of Alpha-Arylphorin In The Heliothis Virescens Midgut Response To Cry1ac Toxin From Bacillus Thuringiensis, Jerreme Jamael Jackson Sep 2019

Characterization Of The Role Of Alpha-Arylphorin In The Heliothis Virescens Midgut Response To Cry1ac Toxin From Bacillus Thuringiensis, Jerreme Jamael Jackson

Jerreme Jackson

Homeostasis of the intestinal epithelium in Heliothis virescens is mediated by the proliferation and differentiation of multipotent intestinal stem cells (ISCs) that lie adjacent to the basal lamina. In response to extrinsic and intrinsic signals, ISC proliferation and differentiation promotes epithelial growth and regeneration following the loss of integrity. We tested the in vivo effects of the ISC mitogen, a [alpha]-arylphorin, on ISC proliferation and the morphological changes of the midgut during larval development. Additionally, we examined how these changes affected the intestinal epithelium response to Cry1Ac toxin from Bacillus thuringiensis. Histological and in vitro evidence supported two distinct ...


Distinct Transcriptional Roles For Histone H3-K56 Acetylation During The Cell Cycle In Yeast, Salih Topal, Pauline Vasseur, Marta Radman-Livaja, Craig L. Peterson Sep 2019

Distinct Transcriptional Roles For Histone H3-K56 Acetylation During The Cell Cycle In Yeast, Salih Topal, Pauline Vasseur, Marta Radman-Livaja, Craig L. Peterson

Open Access Articles

Dynamic disruption and reassembly of promoter-proximal nucleosomes is a conserved hallmark of transcriptionally active chromatin. Histone H3-K56 acetylation (H3K56Ac) enhances these turnover events and promotes nucleosome assembly during S phase. Here we sequence nascent transcripts to investigate the impact of H3K56Ac on transcription throughout the yeast cell cycle. We find that H3K56Ac is a genome-wide activator of transcription. While H3K56Ac has a major impact on transcription initiation, it also appears to promote elongation and/or termination. In contrast, H3K56Ac represses promiscuous transcription that occurs immediately following replication fork passage, in this case by promoting efficient nucleosome assembly. We also detect ...


Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani Sep 2019

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani

Sure-J: Science Undergraduate Research Journal

Background
Breast cancer is a heterogeneous disease that consists of varying genetic, cellular and molecular subtypes with unique characteristics. Due to the multiple subtypes and molecular markers of breast cancer, successful clinical treatment is hampered by the lack of reliable biomarkers. HER2-positive breast cancer is an aggressive subtype associated with poor patient prognosis. Although survival rates have dramatically increased due to the development of Trastuzumab in 1997, many patients develop a resistance to this therapeutic treatment and relapse over time. Rani et al. (2014), have associated the acquirement of resistance to HER2-treatment with Neuromedin U, but the mechanisms by which ...


Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall Sep 2019

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance ...


Gene Pyramids And The Balancing Act Of Keeping Pests At Bay, Gustavo C. Macintosh Sep 2019

Gene Pyramids And The Balancing Act Of Keeping Pests At Bay, Gustavo C. Macintosh

Biochemistry, Biophysics and Molecular Biology Publications

Pyramiding R genes is a common strategy used by breeders to enhance resistance and increase durability of resistance in crops. However, the molecular mechanisms that mediate R gene interactions are not known. Kamphuis et al. (2019) analyzed Medicago truncatula plants carrying two genes that confer resistance to bluegreen aphids. They identified a potential phytohormone crosstalk triggered by the combined R gene action in response to aphid feeding that enhances resistance and minimizes R gene-associated fitness costs to the plant.


The Central Role Of The Tail In Switching Off 10s Myosin Ii Activity, Shixin Yang, Kyounghwan Lee, John L. Woodhead, Osamu Sato, Mitsuo Ikebe, Roger Craig Sep 2019

The Central Role Of The Tail In Switching Off 10s Myosin Ii Activity, Shixin Yang, Kyounghwan Lee, John L. Woodhead, Osamu Sato, Mitsuo Ikebe, Roger Craig

Radiology Publications and Presentations

Myosin II is a motor protein with two heads and an extended tail that plays an essential role in cell motility. Its active form is a polymer (myosin filament) that pulls on actin to generate motion. Its inactive form is a monomer with a compact structure (10S sedimentation coefficient), in which the tail is folded and the two heads interact with each other, inhibiting activity. This conformation is thought to function in cells as an energy-conserving form of the molecule suitable for storage as well as transport to sites of filament assembly. The mechanism of inhibition of the compact molecule ...


Atf6alpha Impacts Cell Number By Influencing Survival, Death And Proliferation, Rohit B. Sharma, Jarin T. Snyder, Laura C. Alonso Sep 2019

Atf6alpha Impacts Cell Number By Influencing Survival, Death And Proliferation, Rohit B. Sharma, Jarin T. Snyder, Laura C. Alonso

Open Access Articles

BACKGROUND: A growing body of literature suggests the cell-intrinsic activity of Atf6alpha during ER stress responses has implications for tissue cell number during growth and development, as well as in adult biology and tumorigenesis [1]. This concept is important, linking the cellular processes of secretory protein synthesis and endoplasmic reticulum stress response with functional tissue capacity and organ size. However, the field contains conflicting observations, especially notable in secretory cell types like the pancreatic beta cell.

SCOPE OF REVIEW: Here we summarize current knowledge of the basic biology of Atf6alpha, along with the pleiotropic roles Atf6alpha plays in cell life ...


Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty Aug 2019

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty

Dissertations

The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) compromises multiple copies of three enzymes - 2-oxoglutarate dehydrogenase (E1o), dihydrolipoyl succinyltransferase (E2o), and dihydrolipoyl dehydrogenase (E3). OGDHc is found in the Krebs cycle and catalyzes the formation of the all-important succinyl-Coenzyme A (succinyl-CoA). OGDHc was engineered to understand the catalytic mechanism and optimized for chemical synthetic goals.

Succinyl-CoA formation takes place within the catalytic domain of E2o via a transesterification reaction. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of CoA. Mechanistic studies were designed to investigate enzymatic transthioesterification. His375 and Asp374 was shown to be ...


A Unified Encyclopedia Of Human Functional Dna Elements Through Fully Automated Annotation Of 164 Human Cell Types, Maxwell W. Libbrecht, Oscar L. Rodriguez, Zhiping Weng, Jeffrey A. Bilmes, Michael M. Hoffman, William Stafford Noble Aug 2019

A Unified Encyclopedia Of Human Functional Dna Elements Through Fully Automated Annotation Of 164 Human Cell Types, Maxwell W. Libbrecht, Oscar L. Rodriguez, Zhiping Weng, Jeffrey A. Bilmes, Michael M. Hoffman, William Stafford Noble

Open Access Articles

Semi-automated genome annotation methods such as Segway take as input a set of genome-wide measurements such as of histone modification or DNA accessibility and output an annotation of genomic activity in the target cell type. Here we present annotations of 164 human cell types using 1615 data sets. To produce these annotations, we automated the label interpretation step to produce a fully automated annotation strategy. Using these annotations, we developed a measure of the importance of each genomic position called the "conservation-associated activity score." We further combined all annotations into a single, cell type-agnostic encyclopedia that catalogs all human regulatory ...


Mechanism For Apobec3g Catalytic Exclusion Of Rna And Non-Substrate Dna, William C. Solomon, Wazo Myint, Shurong Hou, Tapan Kanai, Rashmi Tripathi, Nese Kurt Yilmaz, Celia A. Schiffer, Hiroshi Matsuo Aug 2019

Mechanism For Apobec3g Catalytic Exclusion Of Rna And Non-Substrate Dna, William C. Solomon, Wazo Myint, Shurong Hou, Tapan Kanai, Rashmi Tripathi, Nese Kurt Yilmaz, Celia A. Schiffer, Hiroshi Matsuo

Schiffer Lab Publications

The potent antiretroviral protein APOBEC3G (A3G) specifically targets and deaminates deoxycytidine nucleotides, generating deoxyuridine, in single stranded DNA (ssDNA) intermediates produced during HIV replication. A non-catalytic domain in A3G binds strongly to RNA, an interaction crucial for recruitment of A3G to the virion; yet, A3G displays no deamination activity for cytidines in viral RNA. Here, we report NMR and molecular dynamics (MD) simulation analysis for interactions between A3Gctd and multiple substrate or non-substrate DNA and RNA, in combination with deamination assays. NMR ssDNA-binding experiments revealed that the interaction with residues in helix1 and loop1 (T201-L220) distinguishes the binding mode of ...


Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano Aug 2019

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano

Open Access Articles

JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids ...


Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli Aug 2019

Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli

Electronic Thesis and Dissertation Repository

Elevated plasma lipoprotein(a) (Lp(a)) is the most prevalent heritable risk factor in the development of cardiovascular disease. The apolipoprotein(a) (apo(a)) component of Lp(a) is strongly implicated in the pathogenicity of Lp(a). It is hypothesized that the inflammatory potential of Lp(a)/apo(a) is mediated by the lysine binding ability of the apo(a) kringle IV10 (KIV10) domain, along with its covalently bound oxidized phospholipid (oxPL). Using targeted mutagenesis, two novel null alleles for the LPA gene that generate non-secretable apo(a) species have been identified, resulting from amino acid substitutions in the KIV10 ...


Janani Subramaniam Thesis.Pdf, Janani Subramaniam Aug 2019

Janani Subramaniam Thesis.Pdf, Janani Subramaniam

Janani Subramaniam

Distinctly organized domains of receptors, ion channels, transporters, signaling molecules, cell adhesion molecules, and contractile proteins are crucial to cardiac function. Interactions between adaptor proteins such as ankyrins and cytoskeletal proteins such as obscurin play a pivotal role in organizing these functional domains in cardiomyocytes. Therefore, dysfunction of both ankyrin as well as obscurin lead to a host of cardiovascular diseases such as arrhythmias and cardiomyopathies. Alternative splicing of ankyrin yields numerous isoforms that interact with obscurin at various sub-cellular domains. And while some of these obscurin-ankyrin complexes have been studied, many others have not been characterized. Further, previous studies ...


Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw Aug 2019

Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw

Open Access Articles

The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma ...


Iron-Sulfur Cluster Assembly; In Vivo Analysis Of The Methanogenic Suf System, Evan Dunkle Aug 2019

Iron-Sulfur Cluster Assembly; In Vivo Analysis Of The Methanogenic Suf System, Evan Dunkle

LSU Master's Theses

Iron-sulfur (Fe-S) clusters are among the most ancient and prevalent of all biological cofactors. Their assembly into associated proteins is a tightly regulated process with many organisms employing multiple cluster assembly pathways. Much is known about Fe-S cluster assembly in aerobic organisms such as Escherichia coli (E. coli) but little is known in regards to cluster assembly in more ancient organisms such as methanogens. Methanogens are members of the domain of Archaea and are defined by their ability to generate methane as a byproduct of their main energy generating pathway. Methanogens also have significantly higher Fe-S cluster content compared to ...