Biochemistry, Biophysics, and Structural Biology Commons^™

Explicit Time Deficit In Schizophrenia: Systematic Review And Meta-Analysis Indicate It Is Primary And Not Domain Specific, V Ciullo, G Spalletta, C Caltagirone, Re Jorge, F Piras

Faculty, Staff and Students Publications

Although timing deficits are a robust finding in schizophrenia (SZ), the notion of a genuine time perception disorder in SZ is still being debated because distortions in timing might depend on neuropsychological deficits that are characteristics of the illness. Here we used meta-analytic methods to summarize the evidence of timing deficits in SZ and moderator analyses to determine whether defective timing in SZ arises from nontemporal sources or from defective time perception. PubMed Services, PsycNET, and Scopus were searched through March 2015, and all references in articles were investigated to find other relevant studies. Studies were selected if they included …

Identification Of An Association Of Tnfaip3 Polymorphisms With Matrix Metalloproteinase Expression In Fibroblasts In An Integrative Study Of Systemic Sclerosis-Associated Genetic And Environmental Factors*, Peng Wei, Yang Yang, Xinjian Guo, Nainan Hei, Syeling Lai, Shervin Assassi, Mengyuan Liu, Filemon Tan, Xiaodong Zhou

Faculty, Staff and Students Publications

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.

METHODS: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis …

Ct-Based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring For Fracture Prediction In Metastatic Femoral Lesions, Ta Damron, A Nazarian, V Entezari, C Brown, W Grant, N Calderon, Et Al.

Faculty, Staff and Students Publications

BACKGROUND: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy. QUESTIONS/PURPOSES: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and …

Is Whole-Exome Sequencing An Ethically Disruptive Technology? Perspectives Of Pediatric Oncologists And Parents Of Pediatric Patients With Solid Tumors, Laurence B Mccullough, Melody J Slashinski, Amy L Mcguire, Richard L Street, Christine M Eng, Richard A Gibbs, D William Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive.

PROCEDURE: As a part of the Baylor Advancing Sequencing in Childhood Cancer Care study, we conducted semistructured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis …

Engineered Protein Polymer-Gold Nanoparticle Hybrid Materials For Small Molecule Delivery, Min Dai, Ja Frezzo, E Sharma, R Chen, N Singh, C Yuvienco, E Caglar, S Xiao, A Saxena, Jk Montclare

Publications and Research

We have fabricated protein polymer-gold nanoparticle (P-GNP) nanocomposites that exhibit enhanced binding and delivery properties of the small hydrophobic molecule drug, curcumin, to the model breast cancer cell line, MCF-7. These hybrid biomaterials are constructed via in situ GNP templated-synthesis with genetically engineered histidine tags. The P-GNP nanocomposites exhibit enhanced small molecule loading, sustained release and increased uptake by MCF-7 cells. When compared to the proteins polymers alone, the P-GNPs demonstrate a greater than 7-fold increase in curcumin binding, a nearly 50% slower release profile and more than 2-fold increase in cellular uptake of curcumin. These results suggest that P-GNP …

Structures Of Eccb1 And Eccd1 From The Core Complex Of The Mycobacterial Esx-1 Type Vii Secretion System, Jonathan Mark Wagner, Sum Chan, Timothy J. Evans, Sara Kahng, Jennifer Kim, Mark A. Arbing, David Eisenberg, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Background: The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system.

Results: This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB₁ and EccD₁. The periplasmic domain of EccB₁ consists of 4 repeat domains and a central domain, which together form a quasi …

Prioritizing Variants In Complete Hereditary Breast And Ovarian Cancer (Hboc) Genes In Patients Lacking Known Brca Mutations., Natasha G Caminsky, Eliseos J Mucaki, Ami M Perri, Ruipeng Lu, Joan H M Knoll, Peter K Rogan

Biochemistry Publications

BRCA1 and BRCA2 testing for Hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including non-coding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize non-coding variants of uncertain significance (VUS) in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common …

Efn-4 Functions In Lad-2-Mediated Axon Guidance In Caenorhabditis Elegans, Alicia A. Schwieterman, Cory J. Donelson, Jonathan L. Mcmurry, Martin L. Hudson

Faculty Articles

During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for theC. elegansephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with theC. elegansdivergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to …

Role Of Flippases In Protein Glycosylation In The Endoplasmic Reticulum, Jeffrey S. Rush

Molecular and Cellular Biochemistry Faculty Publications

Glycosylation is essential to the synthesis, folding, and function of glycoproteins in eukaryotes. Proteins are co- and posttranslationally modified by a variety of glycans in the endoplasmic reticulum (ER); modifications include C- and O-mannosylation, N-glycosylation, and the addition of glycosylphosphatidylinositol membrane anchors. Protein glycosylation in the ER of eukaryotes involves enzymatic steps on both the cytosolic and lumenal surfaces of the ER membrane. The glycans are first assembled as precursor glycolipids, on the cytosolic surface of the ER, which are tethered to the membrane by attachment to a long-chain polyisoprenyl phosphate (dolichol) containing a reduced α-isoprene. The lipid-anchored building blocks …

Concentration And Ratio Of Essential Fatty Acids Influences The Inflammatory Response In Lipopolysaccharide Challenged Mice, Korry J. Hintze, J. Tawzer, Robert E. Ward

Nutrition, Dietetics, and Food Sciences Faculty Publications

The goal of this study was to evaluate the role of both the % of dietary, 18-carbon PUFA (2.5%, 5% and 10%) and the n-6:n-3 ratio (1:1, 10:1 and 20:1) on the acute inflammatory response. Mice were fed diets for 8 weeks and injected intraperitoneally with LPS to induce acute inflammation. After 24. h mice were sacrificed and plasma cytokines measured. Diets significantly affected the erythrocyte PUFA composition and the effect of PUFA ratio was more prominent than of PUFA concentration. The % dietary PUFA affected feed efficiency (p

Involvement Of Parp1 In The Regulation Of Alternative Splicing, Elena Matveeva, John Maiorano, Qingyang Zhang, Abdallah M. Eteleeb, Paolo Convertini, Jing Chen, Vittoria Infantino, Stefan Stamm, Jiping Wang, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing. In light of these studies, we hypothesized that …

Acellular Reactivity Of Polymeric Dendrimer Nanoparticles As An Indicator Of Oxidative Stress In Vitro, Marcus Maher, Humza Khalid, Hugh Byrne

Articles

The need for rapid and cost effective pre-screening protocols of the toxicological response of the vast array of emerging nanoparticle types is apparent and the emerging consensus on the paradigm of oxidative stress by generation of intracellular reactive oxygen species as a primary source of the toxic response suggests the development of acellular assays to screen for nanoparticle surface reactivity. This study explores the potential of the monoamine oxidase A (MAO-A) enzyme based assay with polymeric dendrimers as cofactors and serotonin as substrate, which generates H₂O₂, quantified by the conversion of the Carboxy-H₂DCFDA dye …

Bioinformatics Comparison Of M. Ruber Mrub_2507 To E. Coli Pdxk/B1636 And M. Ruber Mrub_2888 To E. Coli Pdxh/B1638 To Determine The Orthologous Nature, Adam Bernardi, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2507 and Mrub_2888. We predict that Mrub_2507 encodes the enzyme pyridoxal kinase (DNA coordinates 2555521..2556402), which is in the Vitamin B₆ Metabolism pathway (KEGG map number 00750). It catalyzes the conversion of pyridoxine, pyridoxamine, or pyridoxal to pyridoxine 5’-phosphate, pyridoxamine 5’-phosphate, or pyridoxal 5’-phosphate respectively. The E. coli K12 MG1655 ortholog is predicted to be b1636, which has …

Comparing Apples And Oranges?: Next Generation Sequencing And Its Impact On Microbiome Analysis, Adam G. Clooney, Fiona Fouhy, Roy D. Sleator, Aisling O'Driscoll, Stanton Catherine, Paul D. Cotter, Marcus J. Claesson

Department of Biological Sciences Publications

Rapid advancements in sequencing technologies along with falling costs present widespread opportunities for microbiome studies across a vast and diverse array of environments. These impressive technological developments have been accompanied by a considerable growth in the number of methodological variables, including sampling, storage, DNA extraction, primer pairs, sequencing technology, chemistry version, read length, insert size, and analysis pipelines, amongst others. This increase in variability threatens to compromise both the reproducibility and the comparability of studies conducted. Here we perform the first reported study comparing both amplicon and shotgun sequencing for the three leading next-generation sequencing technologies. These were applied to …

Targeting An Essential Gtpase Obg For The Development Of Broad-Spectrum Antibiotics, Josephine A. Bonventre, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from …

Targeting Superoxide Dismutase-¬1 In Cancer, Laura Oh, Josh Andersen

Journal of Undergraduate Research

SOD1 is overexpressed in many cancers such as lung adenocarcinoma, non-­ small-­cell lung cancer, and 70% of primary breast cancers. Traditionally, SOD1 is known as an antioxidant in the human body, but only 1% of SOD1 expressed in cells is necessary to keep superoxide radicals below cytotoxic levels, suggesting that SOD1 may have undiscovered functions. One of the known trademarks of cancer is the Warburg Effect defined by up-­regulated glycolysis and down-­ regulated respiration. It is thought that this unique mode of metabolism promotes cancer cell growth. A recent study demonstrated that SOD1 functions to repress respiration through the casein …

Developing A Microfluidic Lab-On-A-Chip Device To Assess The Correlation Between The Ratio Of H And L Ferritin In Maternal Serum And Preterm Birth, Kaitlyn Brower, Adam Woolley

Journal of Undergraduate Research

Preterm birth is the leading cause of death in children under the age of 5¹ and is defined by the Centers for Disease Control as birth before 37 weeks gestation.² It is estimated that 15 million babies are born premature annually and that PTB kills nearly 1 million babies every year. Currently, accurate detection of PTB risk isn’t possible and extrauterine treatments and interventions are insufficient.

Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick J. Cullen, James Curtin

Articles

Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG.

Methods:

Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow …

Learning Chemistry Through Experimentation, Kyle Long, Jennifer Nielson

Journal of Undergraduate Research

For the past five years, Dr. Jennifer Nielson has conducted research in Kampala, Uganda, located in south-central Africa. I have been able to join her for two of the five years, including this past year for nearly three weeks in August. Our research focuses on teaching basic chemistry principle that are difficult to comprehend by using experiments that demonstrate the general concept of atomic structures and functions.

Isothermal Titration Calorimetry Uncovers Substrate Promiscuity Of Bicupin Oxalate Oxidase From Ceriporiopsis Subvermispora, Hassan Rana, Patricia Moussatche, Lis Souza Rocha, Ellen W. Moomaw

Faculty Articles

Isothermal titration calorimetry (ITC) may be used to determine the kinetic parameters of enzymecatalyzed reactions when neither products nor reactants are spectrophotometrically visible and when the reaction products are unknown. We report here the use of the multiple injection method of ITC to characterize the catalytic properties of oxalate oxidase (OxOx) from Ceriporiopsis subvermispora (CsOxOx), a manganese dependent enzyme that catalyzes the oxygen-dependent oxidation of oxalate to carbon dioxide in a reaction coupled with the formation of hydrogen peroxide. CsOxOx is the first bicupin enzyme identified that catalyzes this reaction. The multiple injection ITC method of measuring OxOx activity involves …