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Article ; Online: G × E interactions as a basis for toxicological uncertainty.

Suciu, Ilinca / Pamies, David / Peruzzo, Roberta / Wirtz, Petra H / Smirnova, Lena / Pallocca, Giorgia / Hauck, Christof / Cronin, Mark T D / Hengstler, Jan G / Brunner, Thomas / Hartung, Thomas / Amelio, Ivano / Leist, Marcel

Archives of toxicology

2023 Volume 97, Issue 7, Page(s) 2035–2049

Abstract: To transfer toxicological findings from model systems, e.g. animals, to humans, standardized safety ... on the genetic (G) background of the model (G × E). As a quantitative discipline, toxicology needs to move ... beyond merely qualitative G × E concepts. Research programs are required that determine the major biological ...

Abstract	To transfer toxicological findings from model systems, e.g. animals, to humans, standardized safety factors are applied to account for intra-species and inter-species variabilities. An alternative approach would be to measure and model the actual compound-specific uncertainties. This biological concept assumes that all observed toxicities depend not only on the exposure situation (environment = E), but also on the genetic (G) background of the model (G × E). As a quantitative discipline, toxicology needs to move beyond merely qualitative G × E concepts. Research programs are required that determine the major biological variabilities affecting toxicity and categorize their relative weights and contributions. In a complementary approach, detailed case studies need to explore the role of genetic backgrounds in the adverse effects of defined chemicals. In addition, current understanding of the selection and propagation of adverse outcome pathways (AOP) in different biological environments is very limited. To improve understanding, a particular focus is required on modulatory and counter-regulatory steps. For quantitative approaches to address uncertainties, the concept of "genetic" influence needs a more precise definition. What is usually meant by this term in the context of G × E are the protein functions encoded by the genes. Besides the gene sequence, the regulation of the gene expression and function should also be accounted for. The widened concept of past and present "gene expression" influences is summarized here as G
MeSH term(s)	Humans ; Animals ; Uncertainty ; Adverse Outcome Pathways ; Models, Biological
Language	English
Publishing date	2023-06-01
Publishing country	Germany
Document type	Editorial
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03500-9
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Article: Neonicotinoids with a 6‐chloropyridinyl group (e.g. imidacloprid, acetamiprid, thiacloprid, nitenpyram, boscalid) – Determination of 6‐chloronicotinic acid in urine by GC‐MS : Biomonitoring Methods, 2018

Deutsche Forschungsgemeinschaft. Ständige Senatskommission zur Prüfung Gesundheitsschädlicher Arbeitsstoffe / Gries, Wolfgang / Leng, Gabriele / Hoppe, Hans-Wolfgang / Göen, Thomas / Hartwig, Andrea / MAK Commission

The MAK collection for occupational health and safety, 3(3):1687-1704

2018

Abstract: The working group „Analyses in Biological Materials“ of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area verified the presented biomonitoring method. Neonicotinoids with a 6‐chloropyridinyl ... ...

Institution	Deutsche Forschungsgemeinschaft. Ständige Senatskommission zur Prüfung Gesundheitsschädlicher Arbeitsstoffe
Abstract	The working group „Analyses in Biological Materials“ of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area verified the presented biomonitoring method. Neonicotinoids with a 6‐chloropyridinyl structure are metabolised in warm‐blooded organisms to 6‐chloronicotinic acid that is excreted in urine. This analytical method permits the specific quantification of 6‐chloronicotinic acid in urine. For determination, 2 mL of a urine sample are hydrolysed using 500 µL concentrated hydrochloric acid to cleave the conjugates, which are subsequently extracted with methyl tert‐butyl ether. The solvent is evaporated to dryness under a stream of nitrogen and the residue is dissolved in acetonitrile. Then 6‐chloronicotinic acid is derivatised with hexafluoroisopropanol (HFIP) in the presence of diisopropylcarbodiimide. In a subsequent washing and extraction step, the formed HFIP ester is extracted using isooctane and an aliquot is injected in the GC‐MS system for quantitative analysis. Calibration is performed using calibration standards that are prepared in pooled urine and processed in the same way as the samples to be analysed. The method was extensively validated and the reliability data were confirmed by an independent laboratory, which has established and cross‐checked the whole procedure.
Keywords	6-chloronicotinic acid ; Analyses in Biological Materials ; Acetamiprid ; Boscalid ; Biomonitoring-Methoden ; Biomonitoring Methods ; GC-MS ; Imidacloprid ; Nitenpyram ; Thiacloprid ; biomonitoring ; gas chromatography mass spectrometry ; neonicotinoids ; urine
Language	English
Document type	Article
DOI	10.4126/FRL01-006455598
Database	Repository for Life Sciences

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Book ; Online: G.E. Moore

Moore, G.E / Baldwin, Thomas

Selected Writings

(International Library of Philosophy)

2013

Abstract: G.E. Moore, more than either Bertrand Russell or Ludwig Wittgenstein, was chiefly responsible ...

Series title	International Library of Philosophy
Abstract	G.E. Moore, more than either Bertrand Russell or Ludwig Wittgenstein, was chiefly responsible for the rise of the analytic method in twentieth-century philosophy. This selection of his writings shows Moore at his very best.The classic essays are crucial to major philosophical debates that still resonate today. Amongst those included are:* A Defense of Common Sense* Certainty* Sense-Data* External and Internal Relations* Hume's Theory Explained* Is Existence a Predicate?* Proof of an External WorldIn addition, this collection also contains the key early p
Language	English
Size	Online-Ressource (232 p)
Publisher	Taylor and Francis
Publishing place	Hoboken
Document type	Book ; Online
Note	Description based upon print version of record
ISBN	9780415098533 ; 041509853X
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Prevalence of anti-hepatitis E virus immunoglobulin G in HIV-infected individuals over three decades.

Harritshøj, Lene Holm / Kirkegaard-Klitbo, Ditte Marie / Mejer, Niels / Panum, Inge / Midgley, Sofie Elisabeth / Ullum, Henrik / Benfield, Thomas

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2019 Volume 84, Page(s) 67–72

Abstract: Background: Hepatitis E virus (HEV) genotype 3 is endemic in Europe, and the infection is mostly ...

Abstract	Background: Hepatitis E virus (HEV) genotype 3 is endemic in Europe, and the infection is mostly subclinical or acute and self-limiting. However, persistent infection is described among HIV-infected individuals. The prevalence of antibodies against HEV (anti-HEV) among HIV-infected persons varies geographically and is unknown in Denmark. Rates of co-infection with HEV among HIV-infected individuals in Denmark over three decades, from the early 1980s to 2013, were investigated. Methods: A total of 2506 HIV-infected persons were investigated from two cohorts followed at Hvidovre Hospital, Denmark. Blood samples were tested retrospectively for anti-HEV, including samples from 2216 persons who were enrolled in a prospective clinical cohort and followed between 1995 and 2013, as well as samples from 290 persons from a historical cohort followed between 1980 and 1994. For anti-HEV seroconverting individuals, serial samples were tested for HEV RNA. Factors associated with anti-HEV status were explored using multivariable logistic regression analysis. Results: The overall HEV seroprevalence rates were stable during the 1980s, 1990s, and 2000-2013 (23.1%, 22.9%, and 23.7%, respectively). In all decades, rates of anti-HEV increased with older age, and anti-HEV seropositivity was associated with older generations, HIV risk group, and geographic origin. Persistent HEV infection was not detected in any of 57 individuals with anti-HEV seroconversion. Conclusions: HEV seroprevalence rates were stable in HIV-infected individuals from the early 1980s to 2013. Rates increased with age. No evidence of persistent HEV infection was detected. Infection with HEV is frequent, but persistent HEV infection is rare among HIV-infected individuals.
MeSH term(s)	Adult ; Coinfection/epidemiology ; Female ; HIV Infections/complications ; Hepatitis Antibodies/blood ; Hepatitis E virus/immunology ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; Risk Factors ; Seroepidemiologic Studies
Chemical Substances	Hepatitis Antibodies ; Immunoglobulin G
Language	English
Publishing date	2019-05-04
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2019.04.029
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Article: Schlüssellochrettung aus dem PKW (S.IE.G.E.R-Konzept) – Schritt für Schritt

Tiesmeier, Jens / Südmersen, Rolf / Bachmann-Mennenga, Bernd / Jakob, Thomas

retten!

2019 Volume 8, Issue 02, Page(s) 140–145

Language	German
Publishing date	2019-04-01
Publisher	© Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ISSN	2193-2395 ; 2193-2387
ISSN (online)	2193-2395
ISSN	2193-2387
DOI	10.1055/a-0631-4084
Database	Thieme publisher's database

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Article ; Online: Resveratrol analogue, (E)-N-(2-(4-methoxystyryl) phenyl) furan-2-carboxamide induces G

Cheah, Foo Kit / Leong, Kok Hoong / Thomas, Noel Francis / Chin, Hui Kee / Ariffin, Azhar / Awang, Khalijah

Apoptosis : an international journal on programmed cell death

2018 Volume 23, Issue 5-6, Page(s) 329–342

Abstract: ... which investigates the mechanism underlying the cytotoxic effect of a synthesized resveratrol analogue, (E)-N-(2-(4 ...

Abstract	Resveratrol, a naturally occurring polyphenolic antioxidant, is a potential chemoprophylactic agent for various cancers, including colorectal cancer. Although emerging evidence continually suggests that a number of resveratrol derivatives may be better cancer chemopreventive candidates than resveratrol, studies on the mechanism of action of these derivatives are limited. This is the first study which investigates the mechanism underlying the cytotoxic effect of a synthesized resveratrol analogue, (E)-N-(2-(4-methoxystyryl) phenyl) furan-2-carboxamide (CS) on colorectal cancer. Previously, our group reported a series of synthesized resveratrol analogues, which showed cytotoxicity against a panel of cancer cell lines, in particular on colon cancer cells. In this study, we further discovered that CS also exerts a potent suppressive effect on HCT116 colorectal cancer cells. In contrast, normal colon cells (CCD-112 Con) were not sensitive to CS up to 72 h post treatment. CS caused cytotoxicity in HCT116 cells through several apoptotic events including activation of the Fas death receptor, FADD, caspase 8, caspase 3, caspase 9, and cleaved PARP, which occurred alongside cell cycle arrest from the up-regulation of p53 and p21. The results show that CS causes apoptosis via the activation of an extrinsic pathway leading to caspase activation and cell cycle arrest from activated p53. These findings suggest that CS may be a potential candidate for development as an anti-tumor agent in the future.
MeSH term(s)	Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/drug effects ; Caspases/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Division/drug effects ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Fragmentation ; DNA, Neoplasm/drug effects ; Enzyme Activation ; Furans/pharmacology ; G2 Phase/drug effects ; HCT116 Cells ; Humans ; Reactive Oxygen Species/metabolism ; Resveratrol/analogs & derivatives ; Resveratrol/pharmacology ; Styrenes/pharmacology ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Antineoplastic Agents, Phytogenic ; CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; DNA, Neoplasm ; Furans ; Reactive Oxygen Species ; Styrenes ; Tumor Suppressor Protein p53 ; Tumor Suppressor Proteins ; Caspases (EC 3.4.22.-) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2018-05-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1452360-7
ISSN	1573-675X ; 1360-8185
ISSN (online)	1573-675X
ISSN	1360-8185
DOI	10.1007/s10495-018-1457-8
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Article ; Online: Pinnatoxins E, F and G target multiple nicotinic receptor subtypes.

Hellyer, Shane D / Indurthi, Dinesh / Balle, Thomas / Runder-Varga, Vanda / Selwood, Andrew I / Tyndall, Joel D A / Chebib, Mary / Rhodes, Lesley / Kerr, D Steven

Journal of neurochemistry

2015 Volume 135, Issue 3, Page(s) 479–491

Abstract: ... that pinnatoxins E, F and G, found in New Zealand and Australian shellfish, act as antagonists at muscle-type ... F > G > E. Pinnatoxins F and G also antagonized ACh-evoked responses in α7 and α4β2 neuronal ... receptors expressed in Xenopus oocytes. Molecular modelling revealed that pinnatoxins E, F and G make ...

Abstract	Pinnatoxins are members of the cyclic imine group of marine phycotoxins that are highly toxic in in vivo rodent bioassays, causing rapid death due to respiratory depression. Recent studies have shown that pinnatoxins E, F and G, found in New Zealand and Australian shellfish, act as antagonists at muscle-type nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. In the present study, binding affinities and modes of these pinnatoxin isomers at neuronal and muscle nAChRs were assessed using radioligand binding, electrophysiological and molecular modelling techniques. Radioligand-binding studies revealed that all three pinnatoxins bound with high affinity to muscle-type nAChRs, as well as to the α7 and α4β2 neuronal receptors, with an order of affinity of muscle type > α7 > α4β2. The rank order of potency at all receptors was pinnatoxin F > G > E. Pinnatoxins F and G also antagonized ACh-evoked responses in α7 and α4β2 neuronal receptors expressed in Xenopus oocytes. Molecular modelling revealed that pinnatoxins E, F and G make multiple hydrogen bond interactions with the binding site of muscle-type and α7 receptors, with few interactions at the α4β2 binding site, reflecting the binding affinity and functional data. This study shows for the first time that pinnatoxins E, F and G bind to, and functionally antagonize neuronal nAChRs, with interactions potentially playing a role in pinnatoxin toxicity.
MeSH term(s)	Alkaloids/administration & dosage ; Alkaloids/metabolism ; Animals ; Diaphragm/drug effects ; Diaphragm/metabolism ; Dose-Response Relationship, Drug ; Drug Delivery Systems/methods ; Female ; Protein Binding/physiology ; Protein Subunits/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Nicotinic/metabolism ; Spiro Compounds/administration & dosage ; Spiro Compounds/metabolism ; Xenopus
Chemical Substances	Alkaloids ; Protein Subunits ; Receptors, Nicotinic ; Spiro Compounds ; pinnatoxin E ; pinnatoxin F ; pinnatoxin G
Language	English
Publishing date	2015-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.13245
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Book ; Online: G. E. Moore

Baldwin, Thomas / Preti, Consuelo

early philosophical writings

2011

Abstract: G. E. Moore's fame as a philosopher rests on his ethics of love and beauty, which inspired ...

Institution	ebrary, Inc
Author's details	edited and with an introduction by Thomas Baldwin and Consuelo Preti
Abstract	"G. E. Moore's fame as a philosopher rests on his ethics of love and beauty, which inspired Bloomsbury, and on his 'common sense' certainties, which challenge abstract philosophical theory. Behind these themes lie his critical engagement with Kant's idealist philosophy, which is published here for the first time. These early writings, Moore's fellowship dissertations of 1897 and 1898, show how he initiated his influential break with idealism. In 1897 his main target was Kant's ethics; but by 1898 it was the whole Kantian project of transcendental philosophy that he rejected, and the theory which he developed to replace it gave rise to the new project of philosophy as logical analysis. This edition includes comments by Moore's examiners, Henry Sidgwick, Edward Caird and Bernard Bosanquet, and in a substantial introduction the editors explore the crucial importance of the dissertations to the history of twentieth-century philosophical thought"--
Language	English
Size	Online-Ressource (lxxxv, 251 p), ill
Publisher	Cambridge University Press
Publishing place	Cambridge
Document type	Book ; Online
Note	Includes bibliographic references and index
ISBN	1283020726 ; 1283020785 ; 9780511991967 ; 9780521190145 ; 9781283020787 ; 9781283020725 ; 0511991967 ; 0521190142
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Conference proceedings: Patients’ decision-making in elective intracranial aneurysma treatment – bias of initial counselling (e.g. “anchoring effect”)?

Siller, Sebastian / Kunz, Mathias / Thorsteinsdottir, Jun / Dorn, Franziska / Liebig, Thomas / Tonn, Jörg-Christian / Schichor, Christian

2020 , Page(s) V273

Title translation	Die Entscheidungsfindung des Patienten im Rahmen der elektiven zerebralen Aneurysmaversorgung – Befangenheit durch die Erstberatung (z.B. „Anker-Effekt“)?
Event/congress	71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie; sine loco [digital]; Deutsche Gesellschaft für Neurochirurgie; 2020
Keywords	Medizin, Gesundheit
Publishing date	2020-06-26
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/20dgnc269
Database	German Medical Science

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Article ; Online: Furo[2,3- g]thieno[2,3- e]indole: Application of an Ynamide-Based Benzannulation Strategy to the Synthesis of a Tetracyclic Heteroaromatic Compound.

Forneris, Clarissa C / Wang, Yu-Pu / Mamaliga, Galina / Willumstad, Thomas P / Danheiser, Rick L

Organic letters

2018 Volume 20, Issue 19, Page(s) 6318–6322

Abstract: The first synthesis of the tetracyclic aromatic compound furo[2,3- g]thieno[2,3- e]indole ("FTI ...

Abstract	The first synthesis of the tetracyclic aromatic compound furo[2,3- g]thieno[2,3- e]indole ("FTI") is described. The synthetic strategy features a photochemical benzannulation based on the reaction of an α-diazo ketone and ynamide which assembles a benzothiophene equipped with substituents that enable subsequent cyclizations to generate the nitrogen and oxygen heterocyclic rings.
Language	English
Publishing date	2018-09-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.8b02920
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