Central Role Of Carotid Body Chemoreceptors In Disordered Breathing And Cardiorenal Dysfunction In Chronic Heart Failure.,
2014
University of Nebraska Medical Center
Central Role Of Carotid Body Chemoreceptors In Disordered Breathing And Cardiorenal Dysfunction In Chronic Heart Failure., Noah J. Marcus, Rodrigo Del Rio, Harold D. Schultz
Journal Articles: Cellular & Integrative Physiology
Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. …
The Non-Canonical Hydroxylase Structure Of Yfcm Reveals A Metal Ion-Coordination Motif Required For Ef-P Hydroxylation,
2014
University of Tokyo
The Non-Canonical Hydroxylase Structure Of Yfcm Reveals A Metal Ion-Coordination Motif Required For Ef-P Hydroxylation, Kan Kobayashi, Assaf Katz, Andrei Rajkovic, Ryohei Ishii, Owen E. Branson, Michael A. Freitas, Ryuichiro Ishitani, Michael Ibba, Osamu Nureki
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
EF-P is a bacterial tRNA-mimic protein, which accelerates the ribosome-catalyzed polymerization of poly-prolines. In Escherichia coli, EF-P is post-translationally modified on a conserved lysine residue. The post-translational modification is performed in a two-step reaction involving the addition of a β-lysine moiety and the subsequent hydroxylation, catalyzed by PoxA and YfcM, respectively. The β-lysine moiety was previously shown to enhance the rate of poly-proline synthesis, but the role of the hydroxylation is poorly understood. We solved the crystal structure of YfcM and performed functional analyses to determine the hydroxylation mechanism. In addition, YfcM appears to be structurally distinct from any …
Mistranslation Of The Genetic Code,
2014
The Ohio State University
Mistranslation Of The Genetic Code, Adil Moghal, Kyle Mohler, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
During mRNA decoding at the ribosome, deviations from stringent codon identity, or “mistranslation,” are generally deleterious and infrequent. Observations of organisms that decode some codons ambiguously, and the discovery of a compensatory increase in mistranslation frequency to combat environmental stress have changed the way we view “errors” in decoding. Modern tools for the study of the frequency and phenotypic effects of mistranslation can provide quantitative and sensitive measurements of decoding errors that were previously inaccessible. Mistranslation with non‐protein amino acids, in particular, is an enticing prospect for new drug therapies and the study of molecular evolution.
Relaxed Substrate Specificity Leads To Extensive Trna Mischarging By Streptococcus Pneumoniae Class I And Class Ii Aminoacyl-Trna Synthetases,
2014
The Ohio State University
Relaxed Substrate Specificity Leads To Extensive Trna Mischarging By Streptococcus Pneumoniae Class I And Class Ii Aminoacyl-Trna Synthetases, Jennifer Shepherd, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases provide the first step in protein synthesis quality control by discriminating cognate from noncognate amino acid and tRNA substrates. While substrate specificity is enhanced in many instances by cis- and trans-editing pathways, it has been revealed that in organisms such as Streptococcus pneumoniae some aminoacyl-tRNA synthetases display significant tRNA mischarging activity. To investigate the extent of tRNA mischarging in this pathogen, the aminoacylation profiles of class I isoleucyl-tRNA synthetase (IleRS) and class II lysyl-tRNA synthetase (LysRS) were determined. Pneumococcal IleRS mischarged tRNAIle with both Val, as demonstrated in other bacteria, and Leu in a tRNA sequence-dependent …
Translation Initiation Rate Determines The Impact Of Ribosome Stalling On Bacterial Protein Synthesis,
2014
University of Toronto
Translation Initiation Rate Determines The Impact Of Ribosome Stalling On Bacterial Protein Synthesis, Steven J. Hersch, Sara Elgamal, Assaf Katz, Michael Ibba, William Wiley Navarre
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Ribosome stalling during translation can be caused by a number of characterized mechanisms. However, the impact of elongation stalls on protein levels is variable, and the reasons for this are often unclear. To investigate this relationship, we examined the bacterial translation elongation factor P (EF-P), which plays a critical role in rescuing ribosomes stalled at specific amino acid sequences including polyproline motifs. In previous proteomic analyses of both Salmonella and Escherichia coli efp mutants, it was evident that not all proteins containing a polyproline motif were dependent on EF-P for efficient expression in vivo . The α- and β-subunits of …
Ef-P Dependent Pauses Integrate Proximal And Distal Signals During Translation,
2014
The Ohio State University
Ef-P Dependent Pauses Integrate Proximal And Distal Signals During Translation, Sara Elgamal, Assaf Katz, Steven J. Hersch, David Newsom, Peter White, William Wiley Navarre, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) is required for the efficient synthesis of proteins with stretches of consecutive prolines and other motifs that would otherwise lead to ribosome pausing. However, previous reports also demonstrated that levels of most diprolyl-containing proteins are not altered by the deletion of efp. To define the particular sequences that trigger ribosome stalling at diprolyl (PPX) motifs, we used ribosome profiling to monitor global ribosome occupancy in Escherichia coli strains lacking EF-P. Only 2.8% of PPX motifs caused significant ribosomal pausing in the Δefp strain, with up to a 45-fold increase in ribosome density observed at …
Cryopreservation Of Hepatocyte (Hepg2) Cell Monolayers: Impact Of Trehalose,
2014
Eastern Illinois University
Cryopreservation Of Hepatocyte (Hepg2) Cell Monolayers: Impact Of Trehalose, Blake Stokich, Quinn Osgood, David Grimm, Shhyam Moorthy, Nilay Chakraborty, Michael A. Menze
Faculty Research & Creative Activity
A simple method to cryogenically preserve hepatocyte monolayers is currently not available but such a technique would facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. We investigated the effect of trehalose and dimethyl sulfoxide (Me2SO) in cryopreservation of human hepatocellular carcinoma (HepG2) cells in suspension and monolayer formats. HepG2 cell monolayers were incubated for 24 h at varying concentrations of trehalose (50–150 mM) prior to cryopreservation to identify the optimum concentration for such preincubation. When trehalose alone was used as the cryoprotective agent (CPA), cells in monolayer format did not survive freezing while …
Cryopreservation Of Hepatocyte (Hepg2) Cell Monolayers: Impact Of Trehalose,
2014
Eastern Illinois University
Cryopreservation Of Hepatocyte (Hepg2) Cell Monolayers: Impact Of Trehalose, Blake Stokich, Quinn Osgood, David Grimm, Shhyam Moorthy, Nilay Chakraborty, Michael Menze
Faculty and Staff Scholarship
A simple method to cryogenically preserve hepatocyte monolayers is currently not available but such a technique would facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. We investigated the effect of trehalose and dimethyl sulfoxide (Me2SO) in cryopreservation of human hepatocellular carcinoma (HepG2) cells in suspension and monolayer formats. HepG2 cell monolayers were incubated for 24 h at varying concentrations of trehalose (50–150 mM) prior to cryopreservation to identify the optimum concentration for such preincubation. When trehalose alone was used as the cryoprotective agent (CPA), cells in monolayer format did not survive freezing while …
Osteoblast Oncostatin M Signaling In Modeled Spaceflight,
2014
Boise State University
Osteoblast Oncostatin M Signaling In Modeled Spaceflight, Jacob Goyden
Boise State University Theses and Dissertations
Bone deterioration is a challenge in long-term spaceflight with significant connections to terrestrial disuse bone loss. Prolonged unloading and radiation exposure, defining characteristics of space travel, have both been associated with changes in inflammatory signaling via IL-6 class cytokines in bone. While there is also some evidence for perturbed IL-6 class signaling in spaceflight, there has been scant examination of the connections between free fall, radiation, and inflammatory stimuli in bone. Our lab and others have shown that the IL-6 class cytokine oncostatin M (OSM) is an important regulator of bone remodeling. We hypothesize that spaceflight alters osteoblast OSM signaling, …
The Effect Of Leucine Supplementation On Biomarkers Of Mitochondrial Biogenesis And Protein Synthesis In Soleus Muscle Of Rats Fed A High-Fat Diet,
2014
University of Arkansas, Fayetteville
The Effect Of Leucine Supplementation On Biomarkers Of Mitochondrial Biogenesis And Protein Synthesis In Soleus Muscle Of Rats Fed A High-Fat Diet, Gina Davis
Graduate Theses and Dissertations
Mitochondrial dysfunction is a contributing factor to the advancement of various diseases including obesity, diabetes, and cardiovascular disease. Impairment in mitochondria brings about a diminished mitochondrial number and oxidative capacity. Leucine is known to stimulate muscle protein synthesis through transcription and translation of nuclear DNA leading to increases in mitochondrial biogenesis and fatty acid oxidation. However, the effects of leucine on anabolic factors of the mitochondrial genome, during catabolic conditions are not known. PURPOSE: To determine if leucine supplementation alters the negative effects of a high fat (60%) diet (HFD) on the mitochondrial genome by measuring the gene expression of …
Targeting The Wnt/Β-Catenin Signaling Pathway In Liver Cancer Stem Cells And Hepatocellular Carcinoma Cell Lines With Fh535,
2014
University of Kentucky
Targeting The Wnt/Β-Catenin Signaling Pathway In Liver Cancer Stem Cells And Hepatocellular Carcinoma Cell Lines With Fh535, Roberto Gedaly, Roberto Galuppo, Michael F. Daily, Malay B. Shah, Erin Colleen Maynard, Changguo Chen, Xiping Zhang, Karyn A. Esser, Donald A. Cohen, B. Mark Evers, Jieyun Jiang, Brett T. Spear
Surgery Faculty Publications
Activation of the Wnt/β-catenin pathway has been observed in at least 1/3 of hepatocellular carcinomas (HCC), and a significant number of these have mutations in the β-catenin gene. Therefore, effective inhibition of this pathway could provide a novel method to treat HCC. The purposed of this study was to determine whether FH535, which was previously shown to block the β-catenin pathway, could inhibit β-catenin activation of target genes and inhibit proliferation of Liver Cancer Stem Cells (LCSC) and HCC cell lines. Using β-catenin responsive reporter genes, our data indicates that FH535 can inhibit target gene activation by endogenous and exogenously …
Trnas As Regulators Of Biological Processes,
2014
The Ohio State University
Trnas As Regulators Of Biological Processes, Medha Raina, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Transfer RNAs (tRNA) are best known for their role as adaptors during translation of the genetic code. Beyond their canonical role during protein biosynthesis, tRNAs also perform additional functions in both prokaryotes and eukaryotes for example in regulating gene expression. Aminoacylated tRNAs have also been implicated as substrates for non-ribosomal peptide bond formation, post-translational protein labeling, modification of phospholipids in the cell membrane, and antibiotic biosyntheses. Most recently tRNA fragments, or tRFs, have also been recognized to play regulatory roles. Here, we examine in more detail some of the new functions emerging for tRNA in a variety of cellular processes …
Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code,
2014
The Ohio State University
Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code, Tammy J. Bullwinkle, Noah M. Reynolds, Medha Raina, Adil Moghal, Eleftheria Matsa, Andrei Rajkovic, Huseyin Kayadibi, Farbod Fazlollahi, Christopher Ryan, Nathaniel Howitz, Kym F. Faull, Beth A. Lazazzera, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress …
Smooth Muscle Cell Organization In The Stem Region Of The Gracilis Collateral Circulation,
2014
California Polytechnic State University, San Luis Obispo
Smooth Muscle Cell Organization In The Stem Region Of The Gracilis Collateral Circulation, Amanda Krall
Biomedical Engineering
Many patients who suffer from the ischemic Peripheral Arterial Occlusive Disease (PAOD) experience intermittent claudication, which can be attributed to impaired vasodilation. Collateral vessels are the primary site of resistance to blood flow downstream; therefore maximizing vasodilation in collaterals is crucial for efficient circulation. Collaterals function as natural bypasses around the occluded arteries and the increase in flow into these vessels causes them to outwardly remodel into conduit vessels. However, functional vasodilation in the stem region of collateral vessels is impaired at day 7 following femoral ligation, which can be attributed to smooth muscle cell malfunction. However, the increase in …
Reduced Amino Acid Specificity Of Mammalian Tyrosyl-Trna Synthetase Is Associated With Elevated Mistranslation Of Tyr Codons,
2014
The Ohio State University
Reduced Amino Acid Specificity Of Mammalian Tyrosyl-Trna Synthetase Is Associated With Elevated Mistranslation Of Tyr Codons, Medha Raina, Adil Moghal, Amanda Kano, Mathew Jerums, Paul D. Schnier, Shun Luo, Rohini Deshpande, Pavel D. Bondarenko, Henry Lin, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, …
Adrenergic Signaling Regulates Mitochondrial Ca(2+) Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca(2+) Uniporter.,
2014
Thomas Jefferson University
Adrenergic Signaling Regulates Mitochondrial Ca(2+) Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca(2+) Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu
Center for Translational Medicine Faculty Papers
Abstract Aims: Mitochondrial Ca(2+) homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca(2+) uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca(2+) regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca(2+) entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells. Results: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich …
Eggshell Calcium Regulates Calcium Transport Protein Expression In An Oviparous Snake,
2014
East Tennessee State University
Eggshell Calcium Regulates Calcium Transport Protein Expression In An Oviparous Snake, Hannah Frye
Undergraduate Honors Theses
One hypothesis explaining the numerous independent evolutionary transitions from oviparity to viviparity among squamates (snakes and lizards) proposed that squamate embryonic development is independent of eggshell calcium. Recent research showed at least 25% of the calcium in hatchling oviparous squamates is extracted from the shell. Though not a direct test, these results are inconsistent with the hypothesis. To directly test the hypothesis, we removed eggshell calcium (through peeling) early in development of Pantherophis guttatus (corn snake) eggs. Survivorship to hatching did not differ between peeled and intact eggs. Yet hatchlings from peeled eggs were shorter (273.6 ± 3.4 vs. 261.0 …
Mitoneet: Reduction In Insulin Resistance Through Ameliorated Oxidative Stress?,
2014
Eastern Illinois University
Mitoneet: Reduction In Insulin Resistance Through Ameliorated Oxidative Stress?, Nicolas A. Ferry
Undergraduate Honors Theses
MitoNEET is a mitochondrial iron-sulfur protein with poorly-understood functions. Proposed functions of mitoNEET include regulating of oxidative capacity, reactive oxygen homeostasis, and other possible roles. Investigating the interactions of mitoNEET with other proteins might help identify functional roles of this protein. MitoNEET was discovered in 2004 to identify physiological targets of pioglitazone hydrochloride, a drug that is commonly used to treat type-2 diabetes. Type-2 diabetes is a metabolic disease and, although the exact pathology is complex, the role of the mitochondrion in cellular energy production and glucose oxidation indicates that this organelle has a role in type-2 diabetes. Because of …
Physiological And Biochemical Consequences Of Sleep Deprivation,
2014
Georgia Southern University
Physiological And Biochemical Consequences Of Sleep Deprivation, Jade Catherine Boykin
Honors College Theses
Sleep is a universal phenomenon in vertebrates and lack of sleep has been linked with various abnormal behaviors (Singh et al 2013). Studies have shown that a strong linkage exists between stress and sleep, or lack thereof. In fact, the Better Sleep Council’s 2009 survey revealed that 65% of Americans lose sleep due to elevated stress (Wells and Vaughn 2012). Continual (chronic) elevated stress levels have been linked with serious negative health effects. By using sleep deprivation studies, on a simpler animal model than humans it is our aim to investigate the consequences of sleep deprivation at the physiological and …
The Abcs Of The Ribosome,
2014
The Ohio State University
The Abcs Of The Ribosome, Kurt Fredrick, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
An ABC protein that binds the ribosomal exit site suggests a new mechanism for direct regulation of translation in response to changing ATP levels in the cell.
