Ethanol exposure increases mutation rate through error-prone polymerases

International audienceEthanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes

Low-Dimensional Palladium Nanostructures for Fast and Reliable Hydrogen Gas Detection

Palladium (Pd) has received attention as an ideal hydrogen sensor material due to its properties such as high sensitivity and selectivity to hydrogen gas, fast response, and operability at room temperature. Interestingly, various Pd nanostructures that have been realized by recent developments in nanotechnologies are known to show better performance than bulk Pd. This review highlights the characteristic properties, issues, and their possible solutions of hydrogen sensors based on the low-dimensional Pd nanostructures with more emphasis on Pd thin films and Pd nanowires. The finite size effects, relative strengths and weaknesses of the respective Pd nanostructures are discussed in terms of performance, manufacturability, and practical applicability

The Role of Protein Crystallography in Defining the Mechanisms of Biogenesis and Catalysis in Copper Amine Oxidase

Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O2 to H2O2. These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer’s disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography

De COVID-19-crisis en ongelijkheid op de arbeidsmarkt:Naar een ‘nieuw normaal’met meer of minder ongelijkheden?

De coronacrisis confronteert ons op een extreme manier met een aantal vormen van ongelijkheid die onze arbeidsmarkt kenmerken. In het eerste deel van dit essay identificeren we ongelijkheden die zeer zichtbaar geworden zijn door de coronacrisis, met name de ongelijke waardering van beroepen, ongelijke onzekerheid, de ongelijke fysieke en mentale risico’s verbonden aan werk, en de ongelijke verdeling van zorgtaken. Hierbij wijzen we op manieren waarop deze ongelijkheden verbonden zijn aan sociale identiteiten, zoals gender, etniciteit en handicap. In het tweede deel bespreken we lessen die we uit de crisis kunnen trekken. Als we gewoon trachten terug te keren naar het ‘oude normaal’, zal de arbeidsmarkt gekenmerkt blijven door dezelfde ongelijkheden en zullen de groepen in de meest achtergestelde posities de voornaamste slachtoffers van de crisis worden. We doen daarom een oproep om via organisatie- en overheidsbeleid in te zetten op meer gelijkheid en zo te evolueren naar een ‘nieuw normaal’ dat gekenmerkt wordt door eerlijker gewaardeerd en zekerder werk, en door meer aandacht voor welzijn en zorg

Microbial communities of the house fly Musca domestica vary with geographical location and habitat

House flies (Musca domestica) are widespread, synanthropic filth flies commonly found on decaying matter, garbage, and feces as well as human food. They have been shown to vector microbes, including clinically relevant pathogens. Previous studies have demonstrated that house flies carry a complex and variable prokaryotic microbiota, but the main drivers underlying this variability and the influence of habitat on the microbiota remain understudied. Moreover, the differences between the external and internal microbiota and the eukaryotic components have not been examined. To obtain a comprehensive view of the fly microbiota and its environmental drivers, we sampled over 400 flies from two geographically distinct countries (Belgium and Rwanda) and three different environments-farms, homes, and hospitals. Both the internal as well as external microbiota of the house flies were studied, using amplicon sequencing targeting both bacteria and fungi. Results show that the house fly's internal bacterial community is very diverse yet relatively consistent across geographic location and habitat, dominated by genera Staphylococcus and Weissella. The external bacterial community, however, varies with geographic location and habitat. The fly fungal microbiota carries a distinct signature correlating with the country of sampling, with order Capnodiales and genus Wallemia dominating Belgian flies and genus Cladosporium dominating Rwandan fly samples. Together, our results reveal an intricate country-specific pattern for fungal communities, a relatively stable internal bacterial microbiota and a variable external bacterial microbiota that depends on geographical location and habitat. These findings suggest that vectoring of a wide spectrum of environmental microbes occurs principally through the external fly body surface, while the internal microbiome is likely more limited by fly physiology.status: publishe

Do consumers consider Word of Mouth for crucial life decisions?

This study reexamines the Theory of Reasoned Action in a culture with higher uncertainty avoidance and power distance and analyzes how homophily and the ability (expertise) of word of mouth (WOM) sources impacts on the consumer attitudes and purchase decisions with respect to such high-risk credence products as college selection. By using an interpretivist approach to model building, the study comprises 41 interviews, finding that WOM made a significant impact on attitudes but not on purchase behaviors. Homophily with friends was regarded as an important factor at the search stage, but strong ties were more important in the purchasing of the product. Expertise and the credibility of the WOM played a significant role in generating trust in WOM, resulting in attitude change, although with a minimal impact on purchase behavior. The article concludes with implications for practice

Ethanol exposure increases mutation rate through error-prone polymerases

Ethanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes.Voordeckers K, Colding C, Grasso L, Pardo B, Hoes L, Kominek J, Gielens K, Dekoster K, Gordon J, Van der Zande E, Bircham P, Swings T, Michiels J, Van Loo P, Nuyts S, Pasero P, Lisby M, Verstrepen KJ.Voordeckers K, et al. Among authors: nuyts s. Nat Commun. 2020 Jul 21;11(1):3664. doi: 10.1038/s41467-020-17447-3.Nat Commun. 2020. PMID: 32694532status: publishe