The Structure of Dimethylallyl Tryptophan Synthase Reveals a Common Architecture of Aromatic Prenyltransferases in Fungi and Bacteria
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Determination of Sex 43, Elm Park Gardens, THOSE Who Are Interested in the Heredity of Sex Chelsea, S.W.Lo
APRIL 14, 1934 NATURE 579 sa was correctly computed in five minutes, 510 in genes outweigh the female and the result is the twenty seconds and 610 in seventy seconds. normal haplo-X male." Division was a slower process and 9 digits divided Thus, as my italics show, the experimental by 3 took times varying from two and a half to geneticist seems to agree with what Prof. MacBride seven and three quarters minutes. has expressed in more generally intelligible language ; Square roots of 6 digit numbers were extracted in not only in admitting the essential sameness of sex less than a minute while cube roots took longer. in all organisms but also in understanding the Curiously enough, the memorising of a number of function of proportion in its determination in some 27 digits was not done successfully, although he of them. Unanimity among the different branches of could repeat questions which had been put to him biology has therefore been reached after a long period and their answers after some days had elapsed, and of divergence, from entirely different data and, what would break off calculations in the middle to ask for is more, apparently unawares. Such an event, surely, milk or cigarettes, taking up the calculations again should not be allowed to pass without notice and where he had broken off. His methods of working without applause. The usual view that the chromo were not discovered, but he had obviously memorised some theory of sex determination criticised by the squares of two digit numbers, and less completely MacBride was a special hypothesis put forward by the products of two digit numbers. -
Serotonin Functioning and Adolescents' Alcohol
Development and Psychopathology, 2017, page 1 of 21 # Cambridge University Press 2017 doi:10.1017/S095457941700058X Serotonin functioning and adolescents’ alcohol use: A genetically informed study examining mechanisms of risk FRANCES L. WANG,a LAURIE CHASSIN,a JOHN E. BATES,b DANIELLE DICK,c JENNIFER E. LANSFORD,d e d GREGORY S. PETTIT, AND KENNETH A. DODGE aArizona State University; bIndiana University Bloomington; cVirginia Commonwealth University; dDuke University; and eAuburn University Abstract The current study used data from two longitudinal samples to test whether self-regulation, depressive symptoms, and aggression/antisociality were mediators in the relation between a polygenic score indexing serotonin (5-HT) functioning and alcohol use in adolescence. The results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create 5-HT polygenic risk scores. Adolescents and/or parents reported on adolescents’ self-regulation (Time 1), depressive symptoms (Time 2), aggression/antisociality (Time 2), and alcohol use (Time 3). The results showed that 5-HT polygenic risk did not predict self-regulation. However, adolescents with higher levels of 5-HT polygenic risk showed greater depression and aggression/antisociality. Adolescents’ aggression/antisociality mediated the relation between 5-HT polygenic risk and later alcohol use. Deficits in self- regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. Pathways to alcohol use were especially salient for males from families with low parental education in one of the two samples. The results provide insights into the longitudinal mechanisms underlying the relation between 5-HT functioning and alcohol use (i.e., earlier aggression/antisociality). -
Electrooxidation Enables Highly Regioselective Dearomative Annulation of Indole and Benzofuran Derivatives
ARTICLE https://doi.org/10.1038/s41467-019-13829-4 OPEN Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives Kun Liu1, Wenxu Song1, Yuqi Deng1, Huiyue Yang1, Chunlan Song1, Takfaoui Abdelilah1, Shengchun Wang 1, Hengjiang Cong 1, Shan Tang1 & Aiwen Lei1* 1234567890():,; The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functio- nalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate- determining step. 1 College of Chemistry and Molecular Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, P. R. China. *email: aiwenlei@whu. edu.cn NATURE COMMUNICATIONS | (2020) 11:3 | https://doi.org/10.1038/s41467-019-13829-4 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13829-4 reaking the aromatic systems of electron-rich arenes or fused indolines (Fig. 1a)39–44. Therefore, it is highly appealing to heteroarenes provides three-dimensional chemicals of high develop efficient approaches to allow for their preparation. -
Heterocycles 2 Daniel Palleros
Heterocycles 2 Daniel Palleros Heterocycles 1. Structures 2. Aromaticity and Basicity 2.1 Pyrrole 2.2 Imidazole 2.3 Pyridine 2.4 Pyrimidine 2.5 Purine 3. Π-excessive and Π-deficient Heterocycles 4. Electrophilic Aromatic Substitution 5. Oxidation-Reduction 6. DNA and RNA Bases 7. Tautomers 8. H-bond Formation 9. Absorption of UV Radiation 10. Reactions and Mutations Heterocycles 3 Daniel Palleros Heterocycles Heterocycles are cyclic compounds in which one or more atoms of the ring are heteroatoms: O, N, S, P, etc. They are present in many biologically important molecules such as amino acids, nucleic acids and hormones. They are also indispensable components of pharmaceuticals and therapeutic drugs. Caffeine, sildenafil (the active ingredient in Viagra), acyclovir (an antiviral agent), clopidogrel (an antiplatelet agent) and nicotine, they all have heterocyclic systems. O CH3 N HN O O N O CH 3 N H3C N N HN N OH O S O H N N N 2 N O N N O CH3 N CH3 caffeine sildenafil acyclovir Cl S N CH3 N N H COOCH3 nicotine (S)-clopidogrel Here we will discuss the chemistry of this important group of compounds beginning with the simplest rings and continuing to more complex systems such as those present in nucleic acids. Heterocycles 4 Daniel Palleros 1. Structures Some of the most important heterocycles are shown below. Note that they have five or six-membered rings such as pyrrole and pyridine or polycyclic ring systems such as quinoline and purine. Imidazole, pyrimidine and purine play a very important role in the chemistry of nucleic acids and are highlighted. -
Tryptophan and 5-Hydroxytryptophan for Depression (Review)
Cochrane Database of Systematic Reviews Tryptophan and 5-Hydroxytryptophan for depression (Review) Shaw KA, Turner J, Del Mar C Shaw KA, Turner J, Del Mar C. Tryptophan and 5-Hydroxytryptophan for depression. Cochrane Database of Systematic Reviews 2002, Issue 1. Art. No.: CD003198. DOI: 10.1002/14651858.CD003198. www.cochranelibrary.com Tryptophan and 5-Hydroxytryptophan for depression (Review) Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 3 METHODS ...................................... 3 RESULTS....................................... 4 DISCUSSION ..................................... 4 AUTHORS’CONCLUSIONS . 5 ACKNOWLEDGEMENTS . 5 REFERENCES ..................................... 6 CHARACTERISTICSOFSTUDIES . 10 DATAANDANALYSES. 15 Analysis 1.1. Comparison 1 L-Tryptophan and 5-HTP versus placebo for the treatment of depression, Outcome 1 Numbers ofresponders................................... 15 Analysis 2.1. Comparison 2 Side-effects of L-Tryptophan and 5-HTP versus placebo, Outcome 1 Numbers with side- effects. .................................... 16 FEEDBACK...................................... 16 WHAT’SNEW..................................... 16 HISTORY....................................... 17 CONTRIBUTIONSOFAUTHORS . 17 DECLARATIONSOFINTEREST . 17 SOURCESOFSUPPORT -
Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease
cells Article Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease Chih-Yu Yang 1,2,3,4 , Ting-Wen Chen 5,6 , Wan-Lun Lu 5, Shih-Shin Liang 7,8 , Hsien-Da Huang 5,†, Ching-Ping Tseng 4,5,* and Der-Cherng Tarng 1,3,4,9,* 1 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; [email protected] 2 Stem Cell Research Center, National Yang-Ming University, Taipei 11221, Taiwan 3 Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan 4 Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), Hsinchu 30010, Taiwan 5 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan; [email protected] (T.-W.C.); [email protected] (W.-L.L.); [email protected] (H.-D.H.) 6 Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan 7 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; [email protected] 8 Institute of Biomedical Science, College of Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan 9 Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan * Correspondence: [email protected] (C.-P.T.); [email protected] (D.-C.T.) † Current affiliation: Warshel Institute for Computational Biology, School of Life and Health Sciences, The Chinese University of Hong Kong, Longgang District, Shenzhen 518172, China. Abstract: Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. -
Treating Smoking Dependence in Depressed Alcoholics
Treating Smoking Dependence in Depressed Alcoholics Nassima Ait-Daoud, M.D.; Wendy J. Lynch, Ph.D.; J. Kim Penberthy, Ph.D.; Alison B. Breland, Ph.D.; Gabrielle R. Marzani-Nissen, M.D.; and Bankole A. Johnson, D.Sc., M.D., Ph.D. Alcoholism and nicotine dependence share many neurobiological underpinnings; the presence of one drug can cause a person to crave the other. Depressive illness can complicate comorbid alcohol and nicotine dependence by exacerbating the negative affect encountered during attempts to abstain from one or both drugs. Given the morbidity and mortality associated with cigarette smoking, it is imperative to identify treatments to promote smoking cessation and address comorbid psychiatric conditions contemporaneously. Pharmacotherapeutic options demonstrating varying degrees of efficacy and promise in preclinical and clinical studies include nicotine replacement therapy (NRT), selective serotonin reuptake inhibitors (SSRIs), bupropion, varenicline, tricyclic antidepressants, and bupropion plus NRT. Topiramate has shown potential for promoting smoking cessation in alcoholics, although its safety in depressed patients has not been fully explored. The efficacy of medications for treating nicotine dependence is generally enhanced by the inclusion of behavioral interventions such as cognitive behavioral therapy. When group cohesion and social support are stressed, success rates increase among depressed smokers undergoing smoking cessation treatment. Additional treatment strategies targeting dually dependent individuals with -
L‐Tryptophan As the Origin of Psilocybe Natural Products
Minireviews ChemPlusChem doi.org/10.1002/cplu.202000581 1 2 3 Taking Different Roads: l-Tryptophan as the Origin of 4 5 Psilocybe Natural Products 6 [a] [b] [b] [a] 7 Claudius Lenz, Alexander Sherwood, Robert Kargbo, and Dirk Hoffmeister* 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 ChemPlusChem 2021, 86, 28–35 28 © 2020 The Authors. ChemPlusChem published by Wiley-VCH GmbH Wiley VCH Mittwoch, 30.12.2020 2101 / 181786 [S. 28/35] 1 Minireviews ChemPlusChem doi.org/10.1002/cplu.202000581 1 Psychotropic fungi of the genus Psilocybe, colloquially referred highlighted. Psilocybin and its congeners, the heterogeneous 2 to as „magic mushrooms”, are best known for their l- blue-colored psilocyl oligomers, alongside β-carbolines and 3 tryptophan-derived major natural product, psilocybin. Yet, N,N-dimethyl-l-tryptophan, are presented as well as current 4 recent research has revealed a more diverse secondary knowledge on their biosynthesis is provided. The multidiscipli- 5 metabolism that originates from this amino acid. In this nary character of natural product research is demonstrated, and 6 minireview, the focus is laid on l-tryptophan and the various pharmacological, medicinal, ecological, biochemical, and evolu- 7 Psilocybe natural products and their metabolic routes are tionary aspects are included. 8 9 1. Introduction In this minireview, we focus on the biosynthetic routes of L- 10 tryptophan-derived natural products in Psilocybe mushrooms. -
Ergot Alkaloid Biosynthesis in Aspergillus Fumigatus : Association with Sporulation and Clustered Genes Common Among Ergot Fungi
Graduate Theses, Dissertations, and Problem Reports 2009 Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi Christine M. Coyle West Virginia University Follow this and additional works at: https://researchrepository.wvu.edu/etd Recommended Citation Coyle, Christine M., "Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi" (2009). Graduate Theses, Dissertations, and Problem Reports. 4453. https://researchrepository.wvu.edu/etd/4453 This Dissertation is protected by copyright and/or related rights. It has been brought to you by the The Research Repository @ WVU with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you must obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in WVU Graduate Theses, Dissertations, and Problem Reports collection by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. Ergot alkaloid biosynthesis in Aspergillus fumigatus: Association with sporulation and clustered genes common among ergot fungi Christine M. Coyle Dissertation submitted to the Davis College of Agriculture, Forestry, and Consumer Sciences at West Virginia University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genetics and Developmental Biology Daniel G. Panaccione, Ph.D., Chair Kenneth P. Blemings, Ph.D. Joseph B. -
Organophotocatalytic Dearomatization of Indoles, Pyrroles and Benzo(Thio)Furans Via a Giese-Type Transformation
ARTICLE https://doi.org/10.1038/s42004-021-00460-y OPEN Organophotocatalytic dearomatization of indoles, pyrroles and benzo(thio)furans via a Giese-type transformation Yueteng Zhang1, Peng Ji1, Feng Gao1, Yue Dong1, He Huang2, Changqing Wang1, Ziyuan Zhou3 & ✉ Wei Wang 1 Accessing fascinating organic and biological significant indolines via dearomatization of indoles represents one of the most efficient approaches. However, it has been difficult for the dearomatization of the electron deficient indoles. Here we report the studies leading to 1234567890():,; developing a photoredox mediated Giese-type transformation strategy for the dear- omatization of the indoles. The reaction has been implemented for chemoselectively breaking indolyl C=C bonds embedded in the aromatic system. The synthetic power of this strategy has been demonstrated by using structurally diverse indoles bearing common electron- withdrawing groups including (thio)ester, amide, ketone, nitrile and even aromatics at either C2 or C3 positions and ubiquitous carboxylic acids as radical coupling partner with high trans- stereoselectivity (>20:1 dr). This manifold can also be applied to other aromatic heterocycles including pyrroles, benzofurans and benzothiophenes. Furthermore, enantioselective dear- omatization of indoles has been achieved by a chiral camphorsultam auxiliary with high diastereoselectivity. 1 Departments of Pharmacology and Toxicology and Chemistry and Biochemistry, and BIO5 Institute, University of Arizona, Tucson, AZ, USA. 2 Department of Chemistry and Chemical -
LSD), Which Produces Illicit Market in the USA
DEPENDENCE LIABILITY OF "NON-NARCOTIC 9 DRUGS 81 INDOLES The prototype drug in this subgroup (Table XVI) potentials. Ibogaine (S 212) has appeared in the is compound S 219, lysergide (LSD), which produces illicit market in the USA. dependence of the hallucinogen (LSD) type (see above). A tremendous literature on LSD exists which documents fully the dangers of abuse, which REFERENCES is now widespread in the USA, Canada, the United 304. Sandoz Pharmaceuticals Bibliography on Psychoto- Kingdom, Australia and many western European mimetics (1943-1966). Reprinted by the US countries (for references see Table XVI). LSD must Department of Health, Education, & Welfare, be judged as a very dangerous substance which has National Institute of Mental Health, Washington, no established therapeutic use. D.C. 305. Cerletti, A. (1958) In: Heim, R. & Wasson, G. R., Substances S 200-S 203, S 206, S 208, S 213-S 218 ed., Les champignons hallucinogenes du Mexique, and S 220-S 222 are isomers or congeners of LSD. pp. 268-271, Museum national d'Histoire natu- A number of these are much less potent than LSD in relle, Paris (Etude pharmacologique de la hallucinogenic effect or are not hallucinogenic at all psilocybine) (compounds S 203, S 213, S 216, S 217, S 220 and 306. Cohen, S. (1965) The beyond within. The LSD S 222) and accordingly carry a lesser degree of risk story. Atheneum, New York than LSD. None of these weak hallucinogens has 307. Cohen, S. & Ditman, K. S. (1963) Arch. gen. been abused. Other compounds are all sufficiently Psychiat., 8, 475 (Prolonged adverse reactions to potent to make it likely that they would be abused if lysergic acid diethylamide) 308. -
Risk Assessment of Argyreia Nervosa
Risk assessment of Argyreia nervosa RIVM letter report 2019-0210 W. Chen | L. de Wit-Bos Risk assessment of Argyreia nervosa RIVM letter report 2019-0210 W. Chen | L. de Wit-Bos RIVM letter report 2019-0210 Colophon © RIVM 2020 Parts of this publication may be reproduced, provided acknowledgement is given to the: National Institute for Public Health and the Environment, and the title and year of publication are cited. DOI 10.21945/RIVM-2019-0210 W. Chen (author), RIVM L. de Wit-Bos (author), RIVM Contact: Lianne de Wit Department of Food Safety (VVH) [email protected] This investigation was performed by order of NVWA, within the framework of 9.4.46 Published by: National Institute for Public Health and the Environment, RIVM P.O. Box1 | 3720 BA Bilthoven The Netherlands www.rivm.nl/en Page 2 of 42 RIVM letter report 2019-0210 Synopsis Risk assessment of Argyreia nervosa In the Netherlands, seeds from the plant Hawaiian Baby Woodrose (Argyreia nervosa) are being sold as a so-called ‘legal high’ in smart shops and by internet retailers. The use of these seeds is unsafe. They can cause hallucinogenic effects, nausea, vomiting, elevated heart rate, elevated blood pressure, (severe) fatigue and lethargy. These health effects can occur even when the seeds are consumed at the recommended dose. This is the conclusion of a risk assessment performed by RIVM. Hawaiian Baby Woodrose seeds are sold as raw seeds or in capsules. The raw seeds can be eaten as such, or after being crushed and dissolved in liquid (generally hot water).