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Auxiliary Iron–Sulfur Cofactors in Radical SAM Enzymes☆
Biochimica et Biophysica Acta 1853 (2015) 1316–1334 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamcr Review Auxiliary iron–sulfur cofactors in radical SAM enzymes☆ Nicholas D. Lanz a, Squire J. Booker a,b,⁎ a Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States b Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, United States article info abstract Article history: A vast number of enzymes are now known to belong to a superfamily known as radical SAM, which all contain a Received 19 September 2014 [4Fe–4S] cluster ligated by three cysteine residues. The remaining, unligated, iron ion of the cluster binds in Received in revised form 15 December 2014 contact with the α-amino and α-carboxylate groups of S-adenosyl-L-methionine (SAM). This binding mode Accepted 6 January 2015 facilitates inner-sphere electron transfer from the reduced form of the cluster into the sulfur atom of SAM, Available online 15 January 2015 resulting in a reductive cleavage of SAM to methionine and a 5′-deoxyadenosyl radical. The 5′-deoxyadenosyl Keywords: radical then abstracts a target substrate hydrogen atom, initiating a wide variety of radical-based transforma- – Radical SAM tions. A subset of radical SAM enzymes contains one or more additional iron sulfur clusters that are required Iron–sulfur cluster for the reactions they catalyze. However, outside of a subset of sulfur insertion reactions, very little is known S-adenosylmethionine about the roles of these additional clusters. This review will highlight the most recent advances in the identifica- Cofactor maturation tion and characterization of radical SAM enzymes that harbor auxiliary iron–sulfur clusters. -
Annotation Guidelines for Experimental Procedures
Annotation Guidelines for Experimental Procedures Developed By Mohammed Alliheedi Robert Mercer Version 1 April 14th, 2018 1- Introduction and background information What is rhetorical move? A rhetorical move can be defined as a text fragment that conveys a distinct communicative goal, in other words, a sentence that implies an author’s specific purpose to readers. What are the types of rhetorical moves? There are several types of rhetorical moves. However, we are interested in 4 rhetorical moves that are common in the method section of a scientific article that follows the Introduction Methods Results and Discussion (IMRaD) structure. 1- Description of a method: It is concerned with a sentence(s) that describes experimental events (e.g., “Beads with bound proteins were washed six times (for 10 min under rotation at 4°C) with pulldown buffer and proteins harvested in SDS-sample buffer, separated by SDS-PAGE, and analyzed by autoradiography.” (Ester & Uetz, 2008)). 2- Appeal to authority: It is concerned with a sentence(s) that discusses the use of standard methods, protocols, and procedures. There are two types of this move: - A reference to a well-established “standard” method (e.g., the use of a method like “PCR” or “electrophoresis”). - A reference to a method that was previously described in the literature (e.g., “Protein was determined using fluorescamine assay [41].” (Larsen, Frandesn and Treiman, 2001)). 3- Source of materials: It is concerned with a sentence(s) that lists the source of biological materials that are used in the experiment (e.g., “All microalgal strains used in this study are available at the Elizabeth Aidar Microalgae Culture Collection, Department of Marine Biology, Federal Fluminense University, Brazil.” (Larsen, Frandesn and Treiman, 2001)). -
Supplemental Methods
Supplemental Methods: Sample Collection Duplicate surface samples were collected from the Amazon River plume aboard the R/V Knorr in June 2010 (4 52.71’N, 51 21.59’W) during a period of high river discharge. The collection site (Station 10, 4° 52.71’N, 51° 21.59’W; S = 21.0; T = 29.6°C), located ~ 500 Km to the north of the Amazon River mouth, was characterized by the presence of coastal diatoms in the top 8 m of the water column. Sampling was conducted between 0700 and 0900 local time by gently impeller pumping (modified Rule 1800 submersible sump pump) surface water through 10 m of tygon tubing (3 cm) to the ship's deck where it then flowed through a 156 µm mesh into 20 L carboys. In the lab, cells were partitioned into two size fractions by sequential filtration (using a Masterflex peristaltic pump) of the pre-filtered seawater through a 2.0 µm pore-size, 142 mm diameter polycarbonate (PCTE) membrane filter (Sterlitech Corporation, Kent, CWA) and a 0.22 µm pore-size, 142 mm diameter Supor membrane filter (Pall, Port Washington, NY). Metagenomic and non-selective metatranscriptomic analyses were conducted on both pore-size filters; poly(A)-selected (eukaryote-dominated) metatranscriptomic analyses were conducted only on the larger pore-size filter (2.0 µm pore-size). All filters were immediately submerged in RNAlater (Applied Biosystems, Austin, TX) in sterile 50 mL conical tubes, incubated at room temperature overnight and then stored at -80oC until extraction. Filtration and stabilization of each sample was completed within 30 min of water collection. -
Dysfunctional Γ-Secretase in Familial Alzheimer's Disease
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Neurochem Manuscript Author Res. Author Manuscript Author manuscript; available in PMC 2019 July 01. Published in final edited form as: Neurochem Res. 2019 January ; 44(1): 5–11. doi:10.1007/s11064-018-2511-1. Dysfunctional γ-secretase in familial Alzheimer’s disease Michael S. Wolfe Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045 USA. Abstract Genetics strongly implicate the amyloid β-peptide (Aβ) in the pathogenesis of Alzheimer’s disease. Dominant missense mutation in the presenilins and the amyloid precursor protein (APP) cause early-onset familial Alzheimer’s disease (FAD). As presenilin is the catalytic component of the γ-secretase protease complex that produces Aβ from APP, mutation of the enzyme or substrate that produce Aβ leads to FAD. However, the mechanism by which presenilin mutations cause FAD has been controversial, with gain of function and loss of function offered as binary choices. This overview will instead present the case that presenilins are dysfunctional in FAD. γ-Secretase is a multi-functional enzyme that proteolyzes the APP transmembrane domain in a complex and processive manner. Reduction in a specific function—the carboxypeptidase trimming of initially formed long Aβ peptides containing most of the transmembrane domain to shorter secreted forms —is an emerging common feature of FAD-mutant γ-secretase complexes. Keywords amyloid; protease; genetics; biochemistry Introduction The deposition of extracellular amyloid plaques and neurofibrillary tangles in the brain are cardinal pathological features of Alzheimer’s disease (AD) (Goedert and Spillantini, 2006). The former are composed primarily of the amyloid β-peptide (Aβ), while the latter are comprised of filaments of the otherwise microtubule-associated protein tau. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Hydrogenases of Methanogens
ANRV413-BI79-18 ARI 27 April 2010 21:0 Hydrogenases from Methanogenic Archaea, Nickel, a Novel Cofactor, and H2 Storage Rudolf K. Thauer, Anne-Kristin Kaster, Meike Goenrich, Michael Schick, Takeshi Hiromoto, and Seigo Shima Max Planck Institute for Terrestrial Microbiology, D-35043 Marburg, Germany; email: [email protected] Annu. Rev. Biochem. 2010. 79:507–36 Key Words First published online as a Review in Advance on H2 activation, energy-converting hydrogenase, complex I of the March 17, 2010 respiratory chain, chemiosmotic coupling, electron bifurcation, The Annual Review of Biochemistry is online at reversed electron transfer biochem.annualreviews.org This article’s doi: Abstract 10.1146/annurev.biochem.030508.152103 Most methanogenic archaea reduce CO2 with H2 to CH4. For the Copyright c 2010 by Annual Reviews. activation of H2, they use different [NiFe]-hydrogenases, namely All rights reserved energy-converting [NiFe]-hydrogenases, heterodisulfide reductase- 0066-4154/10/0707-0507$20.00 associated [NiFe]-hydrogenase or methanophenazine-reducing by University of Texas - Austin on 06/10/13. For personal use only. [NiFe]-hydrogenase, and F420-reducing [NiFe]-hydrogenase. The energy-converting [NiFe]-hydrogenases are phylogenetically related Annu. Rev. Biochem. 2010.79:507-536. Downloaded from www.annualreviews.org to complex I of the respiratory chain. Under conditions of nickel limitation, some methanogens synthesize a nickel-independent [Fe]- hydrogenase (instead of F420-reducing [NiFe]-hydrogenase) and by that reduce their nickel requirement. The [Fe]-hydrogenase harbors a unique iron-guanylylpyridinol cofactor (FeGP cofactor), in which a low-spin iron is ligated by two CO, one C(O)CH2-, one S-CH2-, and a sp2-hybridized pyridinol nitrogen. -
Reduced Reelin Expression Accelerates Amyloid-ßplaque
9228 • The Journal of Neuroscience, July 7, 2010 • 30(27):9228–9240 Neurobiology of Disease Reduced Reelin Expression Accelerates Amyloid- Plaque Formation and Tau Pathology in Transgenic Alzheimer’s Disease Mice Samira Kocherhans,1* Amrita Madhusudan,1* Jana Doehner,1* Karin S. Breu,1 Roger M. Nitsch,2 Jean-Marc Fritschy,1 and Irene Knuesel1 1Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland, and 2Division of Psychiatry Research, University of Zurich, CH-8008 Zurich, Switzerland In addition to the fundamental role of the extracellular glycoprotein Reelin in neuronal development and adult synaptic plasticity, alterations in Reelin-mediated signaling have been suggested to contribute to neuronal dysfunction associated with Alzheimer’s disease (AD). In vitro data revealed a biochemical link between Reelin-mediated signaling, Tau phosphorylation, and amyloid precursor protein (APP) processing. To directly address the role of Reelin in amyloid- plaque and Tau pathology in vivo, we crossed heterozygous Reelin knock-out mice (reeler) with transgenic AD mice to investigate the temporal and spatial AD-like neuropathology. We demonstrate that a reduction in Reelin expression results in enhanced amyloidogenic APP processing, as indicated by the precocious production of amyloid- peptides, the significant increase in number and size of amyloid- plaques, as well as age-related aggravation of plaque pathology in double mutant compared with single AD mutant mice of both sexes. Numerous amyloid- plaques accumulate in the hippocampal formation and neocortex of double mutants, precisely in layers with strongest Reelin expression and highest accumulation of Reelin plaques in aged wild-type mice. Moreover, concentric accumulations of phosphorylated Tau-positive neurons around amyloid- plaques were evident in 15-month-old double versus single mutant mice. -
Sequencing, Assembly, and Annotation of the Kaistella Koreensis Genome and Comparison to Closely Related Organisms
Sequencing, Assembly, and Annotation of the Kaistella koreensis Genome and Comparison to Closely Related Organisms Presented to the faculty of Lycoming College in partial fulfillment of the requirements for Departmental Honors in Biology by Timothy Hostelley Lycoming College April 22, 2013 Approved by: (Signature) (Signature) (Signature) (Signature) Abstract Advances in DNA sequencing technology have made DNA sequencing cheaper and more efficient. As a result, there has been an enormous increase in the number of genomes being sequenced. The sequence data can be assembled into complete genomes and annotated in order to reveal information about the organism’s physiology. In this study the DNA of the bacterium Kaistella koreensis was sequenced and assembled into 578 contigs, these contigs were then uploaded to Rapid Annotation Using Subsystems Technology for annotation in order to compute the Average Nucleotide Identity between K. koreensis and closely related organisms in order to dispute the reclassification of K. koreensis as Chryseobacterium koreense. Phenotypic tests including Biolog GenII, API ZYM, and Fatty Acid Methyl Ester analysis were also done in order to supplement the ambiguous results of the ANI. The results of these tests reveal a number of significant differences between K. koreensis and its closest related neighbors that suggests that K. koreensis does not belong in the Chryseobacterium genus or the closely related Lycomia genus. Instead, K. koreensis should be reclassified back to its original classification in the Kaistella genus. This would dispute the proposal made by Kämpfer et al. to reclassify Kaistella koreensis into the Chryseobacterium genus. 1 Introduction DNA sequencing has rapidly evolved from the earliest sequencing efforts using only whole genome shotgun-cloning based sequencing of the 1990’s, to the further advances in Sanger sequencing in the early 2000’s. -
Evaluating the Potential Therapeutic Role of Angiotensin Converting
Evaluating the Potential Therapeutic Role of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for Alzheimer’s Disease using a Drosophila Model by Sarah Gomes A thesis submitted in conformity with the requirements for the degree of Master of Science Institute of Medical Science University of Toronto © Copyright by Sarah Gomes 2017 Evaluating the Potential Therapeutic Role of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for Alzheimer’s Disease using a Drosophila Model Sarah Gomes Master of Science Institute of Medical Science University of Toronto 2017 Abstract Presenilins (PS) play a role in familial Alzheimer’s disease (AD) and Notch signalling. In a genetic screen looking for modifiers of APP but not Notch, we identified Drosophila orthologs of Angiotensin Converting Enzyme (ACE). Interestingly, ACE polymorphisms are associated with AD and Apo-E, the best characterized risk factor for late-onset AD. Moreover, ACE inhibitors (ACE-I) delayed the onset of cognitive impairment and neurodegeneration in mice and humans. However, it remains unclear why ACE-I are beneficial in AD. Here, we explore the link between PS and ACE in a Drosophila model using genetics and pharmacology. We found that ACE disruption does not affect Notch related phenotypes. Moreover, we found that ACE-I and Angiotensin Receptor Blockers are beneficial in an AD Drosophila model. Since inhibition of ACE has no detrimental effects on Notch and modulates AD related phenotypes, it could provide an important therapeutic target for AD. ii Acknowledgments I would like to begin by thanking my supervisor, Gabrielle Boulianne, for her support and guidance. She has not only taught me how to think like a scientist, but also how to create a work- life balance. -
Changes in Soil Microbial Communities After Long-Term Warming Exposure" (2019)
University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations Dissertations and Theses October 2019 CHANGES IN SOIL MICROBIAL COMMUNITIES AFTER LONG- TERM WARMING EXPOSURE William G. Rodríguez-Reillo University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/dissertations_2 Part of the Environmental Microbiology and Microbial Ecology Commons Recommended Citation Rodríguez-Reillo, William G., "CHANGES IN SOIL MICROBIAL COMMUNITIES AFTER LONG-TERM WARMING EXPOSURE" (2019). Doctoral Dissertations. 1757. https://doi.org/10.7275/15007293 https://scholarworks.umass.edu/dissertations_2/1757 This Open Access Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks@UMass Amherst. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. CHANGES IN SOIL MICROBIAL COMMUNITIES AFTER LONG-TERM WARMING EXPOSURE A Dissertation Presented by WILLIAM GABRIEL RODRÍGUEZ-REILLO Submitted to the Graduate School of the University of Massachusetts Amherst in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY SEPTEMBER 2019 Organismic and Evolutionary Biology © Copyright by William Gabriel Rodríguez-Reillo 2019 All Rights Reserved CHANGES IN SOIL MICROBIAL COMMUNITIES AFTER LONG-TERM WARMING EXPOSURE A Dissertation Presented by WILLIAM GABRIEL RODRÍGUEZ-REILLO Approved as to style and content by: _________________________________________ Jeffrey L. Blanchard, Chair _________________________________________ Courtney Babbitt, Member _________________________________________ David Sela, Member _________________________________________ Kristina Stinson, Member ______________________________________ Paige Warren, Graduate Program Director Organismic and Evolutionary Biology DEDICATION To my parents, William Rodriguez Arce and Carmen L. Reillo Batista. A quienes aún en la distancia me mantuvieron en sus oraciones. -
Ubiquitinations in the Notch Signaling Pathway
Int. J. Mol. Sci. 2013, 14, 6359-6381; doi:10.3390/ijms14036359 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Ubiquitinations in the Notch Signaling Pathway Julien Moretti 1 and Christel Brou 2,* 1 Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA; E-Mail: [email protected] 2 Institut Pasteur and CNRS URA 2582, Signalisation Moléculaire et Activation Cellulaire, 25 rue du Docteur Roux, 75724 Paris cedex 15, France * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +33-1-40-61-30-41 Fax: +33-1-40-61-30-40. Received: 1 February 2013; in revised form: 11 March 2013 / Accepted: 14 March 2013 / Published: 19 March 2013 Abstract: The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. Notch activation relies on interactions between neighboring cells, through the binding of Notch receptors to their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade of events eventually transforming the cell surface receptor into a nuclear factor acting on the transcription of specific target genes. This review highlights how the various processes undergone by Notch receptors and ligands that regulate the pathway are linked to ubiquitination events. Keywords: Notch; ubiquitination; deubiquitinating enzyme; signal transduction; trafficking 1. Introduction Development and maintenance of organs and tissues requires constant interaction and communication between cells. One of the major signaling pathways involved in cell-cell communication is the Notch pathway. This pathway is highly conserved in animals as distantly related as C. -
Composition of the Coenzyme F420-Dependent Formate Dehydrogenase from Methanobacterium Formicicum NEIL L
JOURNAL OF BACTERIOLOGY, Feb. 1986, p. 405-411 Vol. 165, No. 2 0021-9193/86/020405-07$02.00/0 Copyright (C 1986, American Society for Microbiology Composition of the Coenzyme F420-Dependent Formate Dehydrogenase from Methanobacterium formicicum NEIL L. SCHAUERt AND JAMES G. FERRY* Department of Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 Received 16 August 1985/Accepted 19 November 1985 The coenzyme F420-dependent formate dehydrogenase from Methanobacterium formicicum was purified to electrophoretic homogeneity by anoxic procedures which included the addition o(f azide, flavin adenine dinucleotide (FAD), glycerol, and 2-mercaptoethanol to all buffer solutions to stabilize iictivity. The enzyme contains, in approximate miolar ratios, 1 FAD molecule and 1 molybdenum, 2 zinc, 21 to 24 iron, and 25 to 29 Downloaded from inorganic sulfur atoms. Denaturation of the enzyme released a molybdopterin cofactor. The enzyme has a molecular weight of 177,000 and consists of one each of two different subunits, giving the composition olol. The molecular weight of the a-subunit is 85,000, and that of the ,-subunit is 53,000. The UV-visible spectrum is typical of nonheme iron-sulfur flavoprotein. Reduction of the enzyme facilitated dissociation of FAD, and the FAD-depleted enzyme was unable to reduce coenzyme F420. Preincubation of the FAD-depleted enzyme with FAD restored coenzyme F420-dependent activity. The methanogenic bacteria are phylogenetically distant Cells were harvested in the late log phase at an optical density from eubacteria and eucaryotes (10). Consistent with this of 3.0 to 4.5 (550 nm, 1-cm light path).