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2017

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Full-Text Articles in Biochemistry

Structural Evidence Of A Major Conformational Change Triggered By Substrate Binding In Dape Enzymes: Impact On The Catalytic Mechanism, Boguslaw Nocek, Cory Reid, Anna Starus, Tahirah Heath, David Bienvenues, Jerzy Osipiuk, Robert Jedrzeczak, Andrzej Joachimiak, Daniel P. Becker Ph.D., Richard C. Holz Dec 2017

Structural Evidence Of A Major Conformational Change Triggered By Substrate Binding In Dape Enzymes: Impact On The Catalytic Mechanism, Boguslaw Nocek, Cory Reid, Anna Starus, Tahirah Heath, David Bienvenues, Jerzy Osipiuk, Robert Jedrzeczak, Andrzej Joachimiak, Daniel P. Becker Ph.D., Richard C. Holz

Chemistry: Faculty Publications and Other Works

The X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ∼50° and shifts ∼10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to …


9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov Dec 2017

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.


Cytochrome B5 Protects Photoreceptors From Light Stress-Induced Lipid Peroxidation And Retinal Degeneration, Xinping Chen, Hana Hall, Jeffrey P. Simpson, Walter D. Leon-Salas, Donald F. Ready, Vikki M. Weake Dec 2017

Cytochrome B5 Protects Photoreceptors From Light Stress-Induced Lipid Peroxidation And Retinal Degeneration, Xinping Chen, Hana Hall, Jeffrey P. Simpson, Walter D. Leon-Salas, Donald F. Ready, Vikki M. Weake

Department of Biochemistry Faculty Publications

Lipid peroxides are generated by oxidative stress in cells, and contribute to ageing and neurodegenerative disease. The eye is at special risk for lipid peroxidation because photoreceptors possess amplified sensory membranes rich in peroxidation-susceptible polyunsaturated fatty acids. Light-induced lipid peroxidation in the retina contributes to retinal degeneration, and lipid peroxidation has been implicated in the progression of age-associated ocular diseases such as age-related macular degeneration (AMD). Here, we show that exposing Drosophila melanogaster to strong blue light induces oxidative stress including lipid peroxidation that results in retinal degeneration. Surprisingly, very young flies are resilient to this acute light stress, suggesting …


Molecular Geometries And Other Properties Of H2o⋯Agi And H3n⋯Agi As Characterised By Rotational Spectroscopy And Ab Initio Calculations, Chris Medcraft, Eva Gougoula, Dror M. Bittner, John C. Mullaney, Susana Blanco, David P. Tew, Nicholas R. Walker, Anthony C. Legon Dec 2017

Molecular Geometries And Other Properties Of H2o⋯Agi And H3n⋯Agi As Characterised By Rotational Spectroscopy And Ab Initio Calculations, Chris Medcraft, Eva Gougoula, Dror M. Bittner, John C. Mullaney, Susana Blanco, David P. Tew, Nicholas R. Walker, Anthony C. Legon

Chemistry & Biochemistry Faculty Publications

The rotational spectra of H3N⋯AgI and H2O⋯AgI have been recorded between 6.5 and 18.5 GHz by chirped-pulse Fourier-transform microwave spectroscopy. The complexes were generated through laser vaporisation of a solid target of silver or silver iodide in the presence of an argon gas pulse containing a low concentration of the Lewis base. The gaseous sample subsequently undergoes supersonic expansion which results in cooling of rotational and vibrational motions such that weakly bound complexes can form within the expanding gas jet. Spectroscopic parameters have been determined for eight isotopologues of H3N⋯AgI and six isotopologues of …


Harmonizing Lipidomics: Nist Interlaboratory Comparison Exercise For Lipidomics Using Srm 1950-Metabolites In Frozen Human Plasma, J Bowden, C Ulmer, C Jones, J Koelmel, L Abdullah, Houli Jiang, Michal Schwartzman, Amaury Cazenave-Gassiot, Antonio Checa, Michelle Cinel, Romain Colas, Serge Cremers, Edward Dennis, James Evans, Alexander Fauland, Jun Han, Houli Jiang, Michal Schwartzman Dec 2017

Harmonizing Lipidomics: Nist Interlaboratory Comparison Exercise For Lipidomics Using Srm 1950-Metabolites In Frozen Human Plasma, J Bowden, C Ulmer, C Jones, J Koelmel, L Abdullah, Houli Jiang, Michal Schwartzman, Amaury Cazenave-Gassiot, Antonio Checa, Michelle Cinel, Romain Colas, Serge Cremers, Edward Dennis, James Evans, Alexander Fauland, Jun Han, Houli Jiang, Michal Schwartzman

NYMC Faculty Publications

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks …


Hydrogen-Bonding-Directed Ordered Assembly Of Carboxylated Poly(3-Alkylthiophene)S, David W. Bilger, Jose A. Figueroa, Neil D. Redeker, Amrita Sarkar, Morgan Stefik, Shanjuu Zhang Nov 2017

Hydrogen-Bonding-Directed Ordered Assembly Of Carboxylated Poly(3-Alkylthiophene)S, David W. Bilger, Jose A. Figueroa, Neil D. Redeker, Amrita Sarkar, Morgan Stefik, Shanjuu Zhang

Faculty Publications

Hydrogen-bonding-induced ordered assembly of poly(3-alkylthiophene)s derivatives bearing carboxylic acid groups has been investigated from diluted and concentrated solutions to solid films using ultraviolet–visible absorption spectroscopy, polarized optical microscopy, and four-point probe conductivity measurements. In dilute solutions, the polymer undergoes a spontaneous structural transition from disordered coil-like to ordered rodlike conformations, which is evidenced by time-dependent chromism. Many factors such as alkyl-chain length, types of solvents, and temperature are studied to understand the assembly behavior. Transition kinetics of the assembly process reveals a universal second-order rate law, indicating an intermolecular origin due to hydrogen bonding. When more concentrated, hydrogen bonding drives …


Blockade Of Cb1 Cannabinoid Receptor Alters Gut Microbiota And Attenuates Inflammation And Diet-Induced Obesity, Pegah Mehrpouya-Bahrami, Kumaraswamy Naidu Chitrala, Mitra S. Ganewatta, Chuanbing Tang, E Angela Murphy, Reilly Enos, Kandy T. Velazquez, Jamie Mccellan, Mitzi Nagarkatti, Prakash Nagarkatti Nov 2017

Blockade Of Cb1 Cannabinoid Receptor Alters Gut Microbiota And Attenuates Inflammation And Diet-Induced Obesity, Pegah Mehrpouya-Bahrami, Kumaraswamy Naidu Chitrala, Mitra S. Ganewatta, Chuanbing Tang, E Angela Murphy, Reilly Enos, Kandy T. Velazquez, Jamie Mccellan, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, inflammatory cytokines …


Defining Electron Bifurcation In The Electron-Transferring Flavoprotein Family, Amaya M. Garcia Costas, Saroj Poudel, Anne-Frances Miller, Gerrit J. Schut, Rhesa N. Ledbetter, Kathryn R. Fixen, Lance C. Seefeldt, Michael W. W. Adams, Caroline S. Harwood, Eric S. Boyd, John W. Peters Nov 2017

Defining Electron Bifurcation In The Electron-Transferring Flavoprotein Family, Amaya M. Garcia Costas, Saroj Poudel, Anne-Frances Miller, Gerrit J. Schut, Rhesa N. Ledbetter, Kathryn R. Fixen, Lance C. Seefeldt, Michael W. W. Adams, Caroline S. Harwood, Eric S. Boyd, John W. Peters

Chemistry Faculty Publications

Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low- and high-potential electrons. It is the third recognized form of energy conservation in biology and was recently described for select electron-transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via Etf-quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer, as well as a non-redox-active AMP. However, Etfs demonstrated to bifurcate electrons contain a second FAD in place of the …


Association Of Vitamin D Deficiency And Vdbp Gene Polymorphism With The Risk Of Ami In A Pakistani Population, Mujtaba Mubashir, Shaheena Anwar, Asal Khan Tareen, Naseema Mehboobali, Khalida Iqbal, Mohammad Iqbal Nov 2017

Association Of Vitamin D Deficiency And Vdbp Gene Polymorphism With The Risk Of Ami In A Pakistani Population, Mujtaba Mubashir, Shaheena Anwar, Asal Khan Tareen, Naseema Mehboobali, Khalida Iqbal, Mohammad Iqbal

Department of Biological & Biomedical Sciences

OBJECTIVE: To investigate the relationship of vitamin D deficiency and risk of AMI in a Pakistani population, and to find out any associationbetween vitamin D binding protein (VDBP) genotypes and risk of AMI in this population.
METHODS: In a comparative cross-sectional study, 246 patients (age: 20-70 years; 171 males and 75 females) with first AMI were enrolled with informed consent. Similarly, 345 healthy adults (230 males and 115 females) were enrolled as controls. Their fasting serum samples were analyzed for 25 (OH) vitamin D, lipids and other biomarkers using kit methods, while DNA was analyzed for VDBP genotypes using PCR-RFLP …


Regenerative Therapy By Replacement Of Stem Cells In Females, Saara Ahmad, Rehana Rehman, Fatima Ahmad Nov 2017

Regenerative Therapy By Replacement Of Stem Cells In Females, Saara Ahmad, Rehana Rehman, Fatima Ahmad

Department of Biological & Biomedical Sciences

No abstract provided.


Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel Nov 2017

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation …


The Future Perspective: Metabolomics In Laboratory Medicine For Inborn Errors Of Metabolism, Yana Sandlers Nov 2017

The Future Perspective: Metabolomics In Laboratory Medicine For Inborn Errors Of Metabolism, Yana Sandlers

Chemistry Faculty Publications

Metabolomics can be described as a simultaneous and comprehensive analysis of small molecules in a biological sample. Recent technological and bioinformatics advances have facilitated large-scale metabolomic studies in many areas, including inborn errors of metabolism (IEMs). Despite significant improvements in the diagnosis and treatment of some IEMs, it is still challenging to understand how genetic variation affects disease progression and susceptibility. In addition, a search for new more personalized therapies and a growing demand for tools to monitor the long-term metabolic effects of existing therapies set the stage for metabolomics integration in preclinical and clinical studies. While targeted metabolomics approach …


Using Competition Assays To Quantitatively Model Cooperative Binding By Transcription Factors And Other Ligands., Jacob Peacock, James B Jaynes Nov 2017

Using Competition Assays To Quantitatively Model Cooperative Binding By Transcription Factors And Other Ligands., Jacob Peacock, James B Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: The affinities of DNA binding proteins for target sites can be used to model the regulation of gene expression. These proteins can bind to DNA cooperatively, strongly impacting their affinity and specificity. However, current methods for measuring cooperativity do not provide the means to accurately predict binding behavior over a wide range of concentrations.

METHODS: We use standard computational and mathematical methods, and develop novel methods as described in Results.

RESULTS: We explore some complexities of cooperative binding, and develop an improved method for relating in vitro measurements to in vivo function, based on ternary complex formation. We derive …


High-Throughput Single-Molecule Telomere Characterization, Jennifer Mccaffrey, Eleanor Young, Katy Lassahn, Justin Sibert, Steven Pastor, Harold Riethman, Ming Xiao Nov 2017

High-Throughput Single-Molecule Telomere Characterization, Jennifer Mccaffrey, Eleanor Young, Katy Lassahn, Justin Sibert, Steven Pastor, Harold Riethman, Ming Xiao

Medical Diagnostics & Translational Sciences Faculty Publications

We have developed a novel method that enables global subtelomere and haplotype-resolved analysis of telomere lengths at the single-molecule level. An in vitro CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human (TTAGGG) n DNA tracts in genomes that have also been barcoded using a separate nickase enzyme that recognizes a 7bp motif genome-wide. High-throughput imaging and analysis of large DNA single molecules from genomes labeled in this fashion using a nanochannel array system permits mapping through subtelomere repeat element (SRE) regions to unique chromosomal DNA while simultaneously measuring the (TTAGGG) n tract length at the end of each …


Association Of Vitamin D Binding Protein Polymorphism With Risk Of Type 2 Diabetes Mellitus In A Pakistani Urban Population: A Case Control Study, Khalida Iqbal, Najmul Islam, Iqbal Azam, Ali Asghar, Naseema Mehboobali, Mohammad Perwaiz Iqbal Nov 2017

Association Of Vitamin D Binding Protein Polymorphism With Risk Of Type 2 Diabetes Mellitus In A Pakistani Urban Population: A Case Control Study, Khalida Iqbal, Najmul Islam, Iqbal Azam, Ali Asghar, Naseema Mehboobali, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

Objective: To assess if genotypes/diplotypes of vitamin D binding protein have any association with type 2 diabetes mellitus.
Methods: This case-control study was conducted from January 2013 to July 2015 at the endocrinology clinics of the Aga Khan University Hospital, Karachi, and comprised adult patients with type 2 diabetes and their age- and gender-matched healthy controls. Venous blood was obtained and assessed for serum/plasma 25 hydroxyvitamin D, parathyroid hormone, calcium, alkaline phosphatase and creatinine. Deoxyribonucleic acid was isolated and genotyping was done by polymerase chain reaction-restriction fragment length polymorphismprocedures.
Results: Of the 330 participants, there were 165(50%) …


Redox-Active Nanomaterials For Nanomedicine Applications, C. M. Sims, S. K. Hanna, D. A. Heller, C. P. Horoszko, M. E. Johnson, A. R. Montoro Bustos, V. Reipa, Kathryn R. Riley, B. C. Nelson Oct 2017

Redox-Active Nanomaterials For Nanomedicine Applications, C. M. Sims, S. K. Hanna, D. A. Heller, C. P. Horoszko, M. E. Johnson, A. R. Montoro Bustos, V. Reipa, Kathryn R. Riley, B. C. Nelson

Chemistry & Biochemistry Faculty Works

Nanomedicine utilizes the remarkable properties of nanomaterials for the diagnosis, treatment, and prevention of disease. Many of these nanomaterials have been shown to have robust antioxidative properties, potentially functioning as strong scavengers of reactive oxygen species. Conversely, several nanomaterials have also been shown to promote the generation of reactive oxygen species, which may precipitate the onset of oxidative stress, a state that is thought to contribute to the development of a variety of adverse conditions. As such, the impacts of nanomaterials on biological entities are often associated with and influenced by their specific redox properties. In this review, we overview …


Prebiotic Rna Network Formation: A Taxonomy Of Molecular Cooperation, Cole Mathis, Sanjay N. Ramprasad, Sara Imari Walker, Niles Lehman Oct 2017

Prebiotic Rna Network Formation: A Taxonomy Of Molecular Cooperation, Cole Mathis, Sanjay N. Ramprasad, Sara Imari Walker, Niles Lehman

Chemistry Faculty Publications and Presentations

Cooperation is essential for evolution of biological complexity. Recent work has shown game theoretic arguments, commonly used to model biological cooperation, can also illuminate the dynamics of chemical systems. Here we investigate the types of cooperation possible in a real RNA system based on the Azoarcusribozyme, by constructing a taxonomy of possible cooperative groups. We construct a computational model of this system to investigate the features of the real system promoting cooperation. We find triplet interactions among genotypes are intrinsically biased towards cooperation due to the particular distribution of catalytic rate constants measured empirically in the real system. For other …


First-Principles And Model Simulation Of All-Optical Spin Reversal, Thomas George, G.P. Zhang, Z. Babyak, Y. Xue, Y. Bai Oct 2017

First-Principles And Model Simulation Of All-Optical Spin Reversal, Thomas George, G.P. Zhang, Z. Babyak, Y. Xue, Y. Bai

Chemistry & Biochemistry Faculty Works

All-optical spin switching is a potential trailblazer for information storage and communication at an unprecedented fast rate free of magnetic fields. However, the current wisdom is largely based on semiempirical models of effective magnetic fields and heat pulses, so it is difficult to provide high-speed design protocols for actual devices. Here, we carry out a massively parallel first-principles and model calculation for 13 spin systems and magnetic layers, free of any effective field, to establish a simpler and alternative paradigm of laser-induced ultrafast spin reversal and to point out a path to a full-integrated photospintronic device. It is the interplay …


Ydj1 Governs Fungal Morphogenesis And Stress Response, And Facilitates Mitochondrial Protein Import Via Mas1 And Mas2, Jinglin L. Xie, Iryna Bohovych, Erin O.Y. Wong, Jean-Philippe Lambert, Anne-Claude Gingras, Oleh Khalimonchuk, Leah E. Cowen, Michelle D. Leach Oct 2017

Ydj1 Governs Fungal Morphogenesis And Stress Response, And Facilitates Mitochondrial Protein Import Via Mas1 And Mas2, Jinglin L. Xie, Iryna Bohovych, Erin O.Y. Wong, Jean-Philippe Lambert, Anne-Claude Gingras, Oleh Khalimonchuk, Leah E. Cowen, Michelle D. Leach

Department of Biochemistry: Faculty Publications

Mitochondria underpin metabolism, bioenergetics, signalling, development and cell death in eukaryotes. Most of the ~1,000 yeast mitochondrial proteins are encoded in the nucleus and synthesised as precursors in the cytosol, with mitochondrial import facilitated by molecular chaperones. Here, we focus on the Hsp40 chaperone Ydj1 in the fungal pathogen Candida albicans, finding that it is localised to both the cytosol and outer mitochondrial membrane, and is required for cellular stress responses and for filamentation, a key virulence trait. Mapping the Ydj1 protein interaction network highlighted connections with co-chaperones and regulators of filamentation. Furthermore, the mitochondrial processing peptidases Mas1 and …


Photosensing And Thermosensing By Phytochrome B Require Both Proximal And Distal Allosteric Features Within The Dimeric Photoreceptor, E Sethe Burgie, Adam N. Bussell, Shu-Hui Lye, Tong Wang, Weiming Hu, Katrice E. Mcloughlin, Erin L. Weber, Huilin Li, Richard D. Vierstra Oct 2017

Photosensing And Thermosensing By Phytochrome B Require Both Proximal And Distal Allosteric Features Within The Dimeric Photoreceptor, E Sethe Burgie, Adam N. Bussell, Shu-Hui Lye, Tong Wang, Weiming Hu, Katrice E. Mcloughlin, Erin L. Weber, Huilin Li, Richard D. Vierstra

Biology Faculty Publications & Presentations

Phytochromes (Phys) encompass a diverse collection of bilin-containing photoreceptors that help plants and microorganisms perceive light through photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic process that enables temperature sensation in plants and possibly other organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled recombinantly, coupled with measurements of solution size, photoconversion, and thermal reversion, we identified both proximal and distal features that influence all three metrics. Included are the downstream C-terminal histidine kinase-related domain known to promote dimerization and a conserved patch just upstream …


1H, 15N, And 13C Chemical Shift Assignments Of The Regulatory Domain Of Human Calcineurin, Dinesh K. Yadav, Sri Ramya Tata, John Hunt, Erik C. Cook, Trevor P. Creamer, Nicholas C. Fitzkee Oct 2017

1H, 15N, And 13C Chemical Shift Assignments Of The Regulatory Domain Of Human Calcineurin, Dinesh K. Yadav, Sri Ramya Tata, John Hunt, Erik C. Cook, Trevor P. Creamer, Nicholas C. Fitzkee

Center for Structural Biology Faculty Publications

Calcineurin (CaN) plays an important role in T-cell activation, cardiac system development and nervous system function. Previous studies have demonstrated that the regulatory domain (RD) of CaN binds calmodulin (CaM) towards the N-terminal end. Calcium-loaded CaM activates the serine/threonine phosphatase activity of CaN by binding to the RD, although the mechanistic details of this interaction remain unclear. It is thought that CaM binding at the RD displaces the auto-inhibitory domain (AID) from the active site of CaN, activating phosphatase activity. In the absence of calcium-loaded CaM, the RD is disordered, and binding of CaM induces folding in the RD. In …


Activation Of The Phospholipid Scramblase Tmem16f By Nanosecond Pulsed Electric Field (Nspef) Facilitates Its Diverse Cytophysiological Effects, Claudia Muratori, Andrei G. Pakhomov, Elena Gianulis, Jade Meads, Maura Casciola, Peter A. Mollica, Olga N. Pakhomova Oct 2017

Activation Of The Phospholipid Scramblase Tmem16f By Nanosecond Pulsed Electric Field (Nspef) Facilitates Its Diverse Cytophysiological Effects, Claudia Muratori, Andrei G. Pakhomov, Elena Gianulis, Jade Meads, Maura Casciola, Peter A. Mollica, Olga N. Pakhomova

Bioelectrics Publications

Nanosecond pulsed electric fields (nsPEF) are emerging as a novel modality for cell stimulation and tissue ablation. However, the downstream protein effectors responsible for nsPEF bioeffects remain to be established. Here we demonstrate that nsPEF activate TMEM16F (or Anoctamin 6), a protein functioning as a Ca2+-dependent phospholipid scramblase and Ca2+-activated chloride channel. Using confocal microscopy and patch clamp recordings, we investigated the relevance of TMEM16F activation for several bioeffects triggered by nsPEF, including phosphatidylserine (PS) externalization, nanopore-conducted currents, membrane blebbing, and cell death. In HEK 293 cells treated with a single 300-ns pulse of 25.5 kV/cm, …


Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang Sep 2017

Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang

FIU Electronic Theses and Dissertations

DNA damage can cause genome instability, which may lead to human cancer. The most common form of DNA damage is DNA base damage, which is efficiently repaired by DNA base excision repair (BER). Thus BER is the major DNA repair pathway that maintains the stability of the genome. On the other hand, BER mediates DNA demethylation that can occur on the promoter region of important tumor suppressor genes such as Breast Cancer 1 (BRCA1) gene that is also involved in prevention and development of cancer. In this study, employing cell-based and in vitro biochemical approaches along with bisulfite DNA sequencing, …


Identification Of Potential Tissue-Specific Cancer Biomarkers And Development Of Cancer Versus Normal Genomic Classifiers, Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar Sep 2017

Identification Of Potential Tissue-Specific Cancer Biomarkers And Development Of Cancer Versus Normal Genomic Classifiers, Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent “OMICS” studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier. Given a sample of a specified tissue type, the single-tissue …


Organ-Specific Regulation Of Atp7a Abundance Is Coordinated With Systemic Copper Homeostasis, Haarin Chun, Tracy Catterson, Heejeong Kim, Jaekwon Lee, Byung-Eun Kim Sep 2017

Organ-Specific Regulation Of Atp7a Abundance Is Coordinated With Systemic Copper Homeostasis, Haarin Chun, Tracy Catterson, Heejeong Kim, Jaekwon Lee, Byung-Eun Kim

Department of Biochemistry: Faculty Publications

Copper (Cu) is an essential cofactor for various enzymatic activities including mitochondrial electron transport, iron mobilization, and peptide hormone maturation. Consequently, Cu dysregulation is associated with fatal neonatal disease, liver and cardiac dysfunction, and anemia. While the Cu transporter ATP7A plays a major role in both intestinal Cu mobilization to the periphery and prevention of Cu over-accumulation, it is unclear how regulation of ATP7A contributes to Cu homeostasis in response to systemic Cu fluctuation. Here we show, using Cu-deficient mouse models, that steadystate levels of ATP7A are lower in peripheral tissues (including the heart, spleen, and liver) under Cu deficiency …


Global Fire Emissions Estimates During 1997-2016, Guido R. Van Der Werf, James T. Randerson, Louis Giglio, Thijs T. Van Leeuwen, Yang Chen, Brendan M. Rogers, Mingquan Mu, Margreet J.E. Van Marle, Douglas C. Morton, G. James Collatz, Robert J. Yokelson, Prasad S. Kasibhatla Sep 2017

Global Fire Emissions Estimates During 1997-2016, Guido R. Van Der Werf, James T. Randerson, Louis Giglio, Thijs T. Van Leeuwen, Yang Chen, Brendan M. Rogers, Mingquan Mu, Margreet J.E. Van Marle, Douglas C. Morton, G. James Collatz, Robert J. Yokelson, Prasad S. Kasibhatla

Chemistry and Biochemistry Faculty Publications

Climate, land use, and other anthropogenic and natural drivers have the potential to influence fire dynamics in many regions. To develop a mechanistic understanding of the changing role of these drivers and their impact on atmospheric composition, long-term fire records are needed that fuse information from different satellite and in situ data streams. Here we describe the fourth version of the Global Fire Emissions Database (GFED) and quantify global fire emissions patterns during 1997-2016. The modeling system, based on the Carnegie-Ames-Stanford Approach (CASA) biogeochemical model, has several modifications from the previous version and uses higher quality input datasets. Significant upgrades …


Special Issue: Intramolecular Hydrogen Bonding 2017, Steve Scheiner Sep 2017

Special Issue: Intramolecular Hydrogen Bonding 2017, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Even after more than a century of study [1–6], scrutiny, and detailed examination, the H-bond continues [7–12] to evoke a level of fascination that surpasses many other phenomena. Perhaps it is the ability of the simple H atom, with but a single electron, to act as a glue that maintains contact between much more complicated species. Or it might be its geometry, which prefers to hold the bridging proton on a direct line between the two heavy atoms. Not to be ignored are the spectral features of the H-bond: the large red shift of the stretching frequency of the covalent …


Genome Structure Of Bacillus Cereus Tsu1 And Genes Involved In Cellulose Degradation And Poly-3-Hydroxybutyrate Synthesis, Hui Li, Suping Zhou, Terrance Johnson, Koen Vercruysse, Lizhi Ouyang, Ranganathan Parthasarathy, Nsoki Phambu, Alexander J. Ropelewski, Theodore W. Thannhauser Sep 2017

Genome Structure Of Bacillus Cereus Tsu1 And Genes Involved In Cellulose Degradation And Poly-3-Hydroxybutyrate Synthesis, Hui Li, Suping Zhou, Terrance Johnson, Koen Vercruysse, Lizhi Ouyang, Ranganathan Parthasarathy, Nsoki Phambu, Alexander J. Ropelewski, Theodore W. Thannhauser

Chemistry Faculty Research

In previous work, we reported on the isolation and genome sequence analysis of Bacillus cereus strain tsu1 NCBI accession number JPYN00000000. The 36 scaffolds in the assembled tsu1 genome were all aligned with B. cereus B4264 genome with variations. Genes encoding for xylanase and cellulase and the cluster of genes in the poly-3-hydroxybutyrate (PHB) biosynthesis pathway were identified in tsu1 genome. The PHB accumulation in B. cereus tsu1 was initially identified using Sudan Black staining and then confirmed using high-performance liquid chromatography. Physical properties of these PHB extracts, when analyzed with Raman spectra and Fourier transform infrared spectroscopy, were found …


Silver Oxide Coatings With High Silver-Ion Elution Rates And Characterization Of Bactericidal Activity., Sarah S Goderecci, Eric Kaiser, Michael Yanakas, Zachary Norris, Jeffrey Scaturro, Robert Oszust, Clarence D Medina, Fallon Waechter, Min Heon, Robert R Krchnavek, Lei Yu, Samuel E Lofland, Renee M Demarest, Gregory A Caputo, Jeffrey D Hettinger Sep 2017

Silver Oxide Coatings With High Silver-Ion Elution Rates And Characterization Of Bactericidal Activity., Sarah S Goderecci, Eric Kaiser, Michael Yanakas, Zachary Norris, Jeffrey Scaturro, Robert Oszust, Clarence D Medina, Fallon Waechter, Min Heon, Robert R Krchnavek, Lei Yu, Samuel E Lofland, Renee M Demarest, Gregory A Caputo, Jeffrey D Hettinger

Faculty Scholarship for the College of Science & Mathematics

This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag₂O, or mixtures of AgO and Ag₂O on surfaces by reactive magnetron sputtering. The coatings demonstrate strong adhesion to many substrate materials and impede the growth of all bacterial strains tested. The coatings are effective in killing Escherichia coli and Staphylococcus aureus, demonstrating a clear zone-of-inhibition against bacteria growing on solid media and the ability to rapidly inhibit bacterial growth in planktonic culture. Additionally, the coatings exhibit very …


Expedited Radiation Biodosimetry By Automated Dicentric Chromosome Identification (Adci) And Dose Estimation, Peter Rogan, Ben Shirley, Yanxin Li, Joan Knoll Sep 2017

Expedited Radiation Biodosimetry By Automated Dicentric Chromosome Identification (Adci) And Dose Estimation, Peter Rogan, Ben Shirley, Yanxin Li, Joan Knoll

Biochemistry Publications

Biological radiation dose can be estimated from dicentric chromosome frequencies in metaphase cells. Performing these cytogenetic dicentric chromosome assays is traditionally a manual, labor-intensive process not well suited to handle the volume of samples which may require examination in the wake of a mass casualty event. Automated Dicentric Chromosome Identifier and Dose Estimator (ADCI) software automates this process by examining sets of metaphase images using machine learning-based image processing techniques. The software selects appropriate images for analysis by removing unsuitable images, classifies each object as either a centromere-containing chromosome or non-chromosome, further distinguishes chromosomes as monocentric chromosomes (MCs) or dicentric …