TY - JOUR A1 - Krumbholz, Julia A1 - Ishida, Keishi A1 - Baunach, Martin A1 - Teikari, Jonna A1 - Rose, Magdalena M. A1 - Sasso, Severin A1 - Hertweck, Christian A1 - Dittmann, Elke T1 - Deciphering chemical mediators regulating specialized metabolism in a symbiotic cyanobacterium JF - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker. International edition N2 - Genomes of cyanobacteria feature a variety of cryptic biosynthetic pathways for complex natural products, but the peculiarities limiting the discovery and exploitation of the metabolic dark matter are not well understood. Here we describe the discovery of two cell density-dependent chemical mediators, nostoclide and nostovalerolactone, in the symbiotic model strain Nostoc punctiforme, and demonstrate their pronounced impact on the regulation of specialized metabolism. Through transcriptional, bioinformatic and labeling studies we assigned two adjacent biosynthetic gene clusters to the biosynthesis of the two polyketide mediators. Our findings provide insight into the orchestration of specialized metabolite production and give lessons for the genomic mining and high-titer production of cyanobacterial bioactive compounds. KW - Biosynthesis KW - Cyanobacteria KW - Genomic Mining KW - Quorum Sensing KW - Specialized KW - Metabolism Y1 - 2022 U6 - https://doi.org/10.1002/anie.202204545 SN - 1433-7851 SN - 1521-3773 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Müller, S. M. A1 - Finke, Hannah A1 - Ebert, Franziska A1 - Kopp, Johannes Florian A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Francesconi, Kevin A. A1 - Raber, G. A1 - Schwerdtle, Tanja T1 - Arsenic-containing hydrocarbons BT - effects on gene expression, epigenetics, and biotransformation in HepG2 cells JF - Archives of toxicology : official journal of EUROTOX N2 - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids. KW - Arsenolipids KW - Gene expression KW - Arsenic-containing hydrocarbons KW - Global DNA methylation KW - Arsenic speciation KW - Metabolism Y1 - 2018 U6 - https://doi.org/10.1007/s00204-018-2194-z SN - 0340-5761 SN - 1432-0738 VL - 92 IS - 5 SP - 1751 EP - 1765 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Montiglio, Pierre-Olivier A1 - Dammhahn, Melanie A1 - Messier, Gabrielle Dubuc A1 - Reale, Denis T1 - The pace-of-life syndrome revisited BT - the role of ecological conditions and natural history on the slow-fast continuum JF - Behavioral ecology and sociobiology N2 - The pace-of-life syndrome (i.e., POLS) hypothesis posits that behavioral and physiological traits mediate the trade-off between current and future reproduction. This hypothesis predicts that life history, behavioral, and physiological traits will covary under clearly defined conditions. Empirical tests are equivocal and suggest that the conditions necessary for the POLS to emerge are not always met. We nuance and expand the POLS hypothesis to consider alternative relationships among behavior, physiology, and life history. These relationships will vary with the nature of predation risk, the challenges posed by resource acquisition, and the energy management strategies of organisms. We also discuss how the plastic response of behavior, physiology, and life history to changes in ecological conditions and variation in resource acquisition among individuals determine our ability to detect a fast-slow pace of life in the first place or associations among these traits. Future empirical studies will provide most insights on the coevolution among behavior, physiology, and life history by investigating these traits both at the genetic and phenotypic levels in varying types of predation regimes and levels of resource abundance. KW - Behavior KW - Immunity KW - Life history strategies KW - Metabolism KW - Personality KW - Trait interaction Y1 - 2018 U6 - https://doi.org/10.1007/s00265-018-2526-2 SN - 0340-5443 SN - 1432-0762 VL - 72 IS - 7 PB - Springer CY - New York ER - TY - JOUR A1 - Ebert, Franziska A1 - Meyer, Sören A1 - Leffers, Larissa A1 - Raber, Georg A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Toxicological characterisation of a thio-arsenosugar-glycerol in human cells JF - Journal of trace elements in medicine and biology N2 - Arsenosugars are water-soluble arsenic species predominant in marine algae and other seafood including mussels and oysters. They typically occur at levels ranging from 2 to 50 mg arsenic/kg dry weight. Most of the arsenosugars contain arsenic as a dimethylarsinoyl group (Me2As(O)-), commonly referred to as the oxo forms, but thio analogues have also been identified in marine organisms and as metabolic products of oxo-arsenosugars. So far, no data regarding toxicity and toxicokinetics of thio-arsenosugars are available. This in vitro-based study indicates that thio-dimethylarsenosugar-glycerol exerts neither pronounced cytotoxicity nor genotoxicity even though this arsenical was bioavailable to human hepatic (HepG2) and urothelial (UROtsa) cells. Experiments with the Caco-2 intestinal barrier model mimicking human absorption indicate for the thio-arsenosugar-glycerol higher intestinal bioavailability as compared to the oxo-arsenosugars. Nevertheless, absorption estimates were much lower in comparison to other arsenicals including arsenite and arsenic-containing hydrocarbons. Arsenic speciation in cell lysates revealed that HepG2 cells are able to metabolise the thio-arsenosugar-glycerol to some extent to dimethylarsinic acid (DMA). These first in vitro data cannot fully exclude risks to human health related to the presence of thio-arsenosugars in food. (C) 2016 Elsevier GmbH. All rights reserved. KW - Arsenic KW - Thio-arsenosugar-glycerol KW - Toxicity KW - Toxicokinetics KW - Genotoxicity KW - Metabolism Y1 - 2016 U6 - https://doi.org/10.1016/j.jtemb.2016.04.013 SN - 0946-672X VL - 38 SP - 150 EP - 156 PB - Springer Publishing Company CY - Jena ER - TY - JOUR A1 - Hortobagyi, Tibor A1 - Lesinski, Melanie A1 - Fernandez-del-Olmo, Miguel A1 - Granacher, Urs T1 - Small and inconsistent effects of whole body vibration on athletic performance: a systematic review and meta-analysis JF - European journal of applied physiology N2 - We quantified the acute and chronic effects of whole body vibration on athletic performance or its proxy measures in competitive and/or elite athletes. Systematic literature review and meta-analysis. Whole body vibration combined with exercise had an overall 0.3 % acute effect on maximal voluntary leg force (-6.4 %, effect size = -0.43, 1 study), leg power (4.7 %, weighted mean effect size = 0.30, 6 studies), flexibility (4.6 %, effect size = -0.12 to 0.22, 2 studies), and athletic performance (-1.9 %, weighted mean effect size = 0.26, 6 studies) in 191 (103 male, 88 female) athletes representing eight sports (overall effect size = 0.28). Whole body vibration combined with exercise had an overall 10.2 % chronic effect on maximal voluntary leg force (14.6 %, weighted mean effect size = 0.44, 5 studies), leg power (10.7 %, weighted mean effect size = 0.42, 9 studies), flexibility (16.5 %, effect size = 0.57 to 0.61, 2 studies), and athletic performance (-1.2 %, weighted mean effect size = 0.45, 5 studies) in 437 (169 male, 268 female) athletes (overall effect size = 0.44). Whole body vibration has small and inconsistent acute and chronic effects on athletic performance in competitive and/or elite athletes. These findings lead to the hypothesis that neuromuscular adaptive processes following whole body vibration are not specific enough to enhance athletic performance. Thus, other types of exercise programs (e.g., resistance training) are recommended if the goal is to improve athletic performance. KW - Exercise KW - Muscle KW - Force KW - Power KW - Skill KW - Reflex KW - Endocrine KW - Metabolism Y1 - 2015 U6 - https://doi.org/10.1007/s00421-015-3194-9 SN - 1439-6319 SN - 1439-6327 VL - 115 IS - 8 SP - 1605 EP - 1625 PB - Springer CY - New York ER - TY - JOUR A1 - Köhler, Yvonne A1 - Luther, Eva Maria A1 - Meyer, Sören A1 - Schwerdtle, Tanja A1 - Dringen, Ralf T1 - Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes JF - Journal of trace elements in medicine and biology N2 - Inorganic arsenicals are environmental toxins that have been connected with neuropathies and impaired cognitive functions. To investigate whether such substances accumulate in brain astrocytes and affect their viability and glutathione metabolism, we have exposed cultured primary astrocytes to arsenite or arsenate. Both arsenicals compromised the cell viability of astrocytes in a time- and concentration-dependent manner. However, the early onset of cell toxicity in arsenite-treated astrocytes revealed the higher toxic potential of arsenite compared with arsenate. The concentrations of arsenite and arsenate that caused within 24 h half-maximal release of the cytosolic enzyme lactate dehydrogenase were around 0.3 mM and 10 mM, respectively. The cellular arsenic contents of astrocytes increased rapidly upon exposure to arsenite or arsenate and reached after 4 h of incubation almost constant steady state levels. These levels were about 3-times higher in astrocytes that had been exposed to a given concentration of arsenite compared with the respective arsenate condition. Analysis of the intracellular arsenic species revealed that almost exclusively arsenite was present in viable astrocytes that had been exposed to either arsenate or arsenite. The emerging toxicity of arsenite 4 h after exposure was accompanied by a loss in cellular total glutathione and by an increase in the cellular glutathione disulfide content. These data suggest that the high arsenite content of astrocytes that had been exposed to inorganic arsenicals causes an increase in the ratio of glutathione disulfide to glutathione which contributes to the toxic potential of these substances. KW - Arsenic KW - Astrocytes KW - GSH KW - Metabolism KW - Toxicity Y1 - 2014 U6 - https://doi.org/10.1016/j.jtemb.2014.04.007 SN - 0946-672X VL - 28 IS - 3 SP - 328 EP - 337 PB - Elsevier CY - Jena ER -