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  • Journals
  • Articles  (1,169)
  • Latest Papers from Table of Contents or Articles in Press  (1,169)
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  • Frontiers Media
  • 2015-2019  (1,169)
  • Mutagenesis  (188)
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  • Biology  (1,169)
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  • Journals
  • Articles  (1,169)
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  • Latest Papers from Table of Contents or Articles in Press  (1,169)
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  • Oxford University Press  (1,169)
  • American Chemical Society (ACS)
  • Frontiers Media
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  • 1
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    Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-20
    Description: It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18–83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16–1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio ( P 〈 0.05) and plasma concentrations of glycosylated hemoglobin ( P = 0.07). However, multivariate regression analysis only showed an inverse association between age and DNA repair activity ( P 〈 0.05), indicating that the decline in repair activity was not mediated by metabolic risk factors. In summary, the results show an inverse association between age and DNA repair activity of oxidatively damaged DNA.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-20
    Description: Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We performed a controlled cross-over, randomised, single-blinded, repeated-measure study where 60 healthy subjects (25 males and 35 females) with age 55–83 years and body mass index above 25kg/m 2 were exposed for 5h to either particle-filtered or sham-filtered air from a busy street with number of concentrations and PM 2.5 levels of 1800/cm 3 versus 23 000/cm 3 and 3 µg/m 3 versus 24 µg/m 3 , respectively. Peripheral blood mononuclear cells (PBMCs) were collected and assayed for production of ROS with and without ex vivo exposure to nanosized carbon black as well as expression of genes related to inflammation ( chemokine (C-C motif) ligand 2 , interleukin-8 and tumour necrosis factor ), oxidative stress response ( heme oxygenase (decycling)-1 ) and DNA repair ( oxoguanine DNA glycosylase ). DNA strand breaks and oxidised purines were assayed by the alkaline comet assay. No statistically significant differences were found for any biomarker immediately after exposure to PM from urban street air although strand breaks and oxidised purines combined were significantly associated with the particle number concentration during exposure. In conclusion, 5h of controlled exposure to PM from urban traffic did not change the gene expression related to inflammation, oxidative stress or DNA repair, ROS production or oxidatively damaged DNA in PBMCs from elderly overweight human subjects.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
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  • 3
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    Sesamol attenuates genotoxicity in bone marrow cells of whole-body {gamma}-irradiated mice (2015)
    Oxford University Press
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    Publication Date: 2015-08-20
    Description: Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only ( P 〈 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 4
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    Cadmium impairs protein folding in the endoplasmic reticulum and induces the unfolded protein response (2016)
    Oxford University Press
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    Publication Date: 2016-07-24
    Description: Cellular exposure to cadmium is known to strongly induce the unfolded protein response (UPR), which suggests that the endoplasmic reticulum (ER) is preferentially damaged by cadmium. According to recent reports, the UPR is induced both dependent on and independently of accumulation of unfolded proteins in the ER. In order to understand the toxic mechanism of cadmium, here we investigated how cadmium exposure leads to Ire1 activation, which triggers the UPR, using yeast Saccharomyces cerevisiae as a model organism. Cadmium poorly induced the UPR when Ire1 carried a mutation that impairs its ability to recognize unfolded proteins. Ire1 activation by cadmium was also attenuated by the chemical chaperone 4-phenylbutyrate. Cadmium caused sedimentation of BiP, the molecular chaperone in the ER, which suggests the ER accumulation of unfolded proteins. A green fluorescent protein-based reporter assay also indicated that cadmium damages the oxidative protein folding in the ER. We also found that an excess concentration of extracellular calcium attenuates the Ire1 activation by cadmium. Taken together, we propose that cadmium exposure leads to the UPR induction through impairment of protein folding in the ER.
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    The effect of linoleic acid on the Sauvignon blanc fermentation by different wine yeast strains (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-24
    Description: The level of linoleic acid in the Sauvignon blanc (SB) grape juice affects the development of different aroma compounds during fermentation by Saccharomyces cerevisiae EC1118, including key varietal thiols such as 3-mercaptohexanol (3MH) and 3-mercaptohexyl acetate (3MHA). However, it is still unknown if linoleic acid would affect in a similar way other commonly used S. cerevisiae wine strains. Here we investigated the effect of grape juice linoleic acid on the development of aroma compounds and other metabolites of SB wines using different wine yeast strains: EC1118, AWRI796 and VIN13. Linoleic acid clearly affected the levels of acetylated aroma compounds, several amino acids, and antioxidant molecules, independent of yeast strain, but the production of 3MH was affected by linoleic acid in a strain-specific manner. Moreover, the supplementation of deuterium-labelled 3MH also affected the production of varietal thiols in a strain-specific way. Linoleic acid reduced the acetylation process probably by inhibiting an acetyltransferase, an effect that was independent of the yeast strain. However, regulation of the 3MH biosynthesis is strain-specific, which suggests a mindful consideration not only towards the wine yeast but also to the linoleic acid concentration in the grape juice in order to obtain the desired wine aroma characteristics.
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Maltose and maltotriose utilisation by group I strains of the hybrid lager yeast Saccharomyces pastorianus (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-24
    Description: Brewer's wort is a challenging environment for yeast as it contains predominantly α-glucoside sugars. There exist two subgroups of the lager yeast Saccharomyces pastorianus which differ in sugar utilisation. We performed wort fermentations and compared representative strains from both groups with respect to their ability to transport and ferment maltose and maltotriose. Additionally, we mapped the transporters MALx1 , AGT1 , MPHx and MTT1 by Southern blotting. Contrary to previous observations, group I comprises a diverse set of strains, with varying ability to transport and ferment maltotriose. Of the eight group I strains, three efficiently utilised maltotriose, a property enabled by the presence of transmembrane transporters SeAGT1 and MTT1 . A58, a variant of the group I type strain (CBS1513) performed particularly well, taking up maltotriose at a higher rate than maltose and retaining significant transport activity at temperatures as low as 0°C. Analysis of transporter distribution in this strain revealed an increased copy number of the MTT1 gene, which encodes the only permease known with higher affinity for maltotriose than maltose and low temperature dependence for transport. We propose that much of the variation in lager yeast fermentation behaviour is determined by the presence or absence of specific transmembrane transporters.
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-24
    Description: Vacuolar H + -ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2 , which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata . The loss of Vph2 resulted in increased H 2 O 2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The vph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl- l -cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase (Sod2) and catalase (Cta1) were decreased in the vph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the vph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V-ATPase in the OSR in C. glabrata .
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
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  • 8
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    The birth of enthusiasm and passion for science (2016)
    Oxford University Press
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    Publication Date: 2016-07-24
    Description: In this paper I describe the main aspects of my career and focus on the retrospective on my life and my work.
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
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  • 9
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    Dissection of quantitative traits by bulk segregant mapping in a protoploid yeast species (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-24
    Description: Since more than a decade ago, Saccharomyces cerevisiae has been used as a model to dissect complex traits, revealing the genetic basis of a large number of traits in fine detail. However, to have a more global view of the genetic architecture of traits across species, the examination of the molecular basis of phenotypes within non-conventional species would undoubtedly be valuable. In this respect, the Saccharomycotina yeasts represent ideal and potential non-model organisms. Here we sought to assess the feasibility of genetic mapping by bulk segregant analysis in the protoploid Lachancea kluyveri (formerly S. kluyveri ) yeast species, a distantly related species to S. cerevisiae . For this purpose, we designed a fluorescent mating-type marker, compatible with any mating-competent strains representative of this species, to rapidly create a large population of haploid segregants (〉10 5 cells). Quantitative trait loci can be mapped by selecting and sequencing an enriched pool of progeny with extreme phenotypic values. As a test bed, we applied this strategy and mapped the causal loci underlying halotolerance phenotypes in L. kluyveri . Overall, this study demonstrates that bulk segregant mapping is a powerful way for investigating the genetic basis of natural variations in non-model yeast organisms and more precisely in L. kluyveri .
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    {alpha},{beta}-Dicarbonyl reduction is mediated by the Saccharomyces Old Yellow Enzyme (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-27
    Description: The undesirable flavor compounds diacetyl and 2,3-pentanedione are vicinal diketones (VDKs) formed by extracellular oxidative decarboxylation of intermediate metabolites of the isoleucine, leucine and valine (ILV) biosynthetic pathway. These VDKs are taken up by Saccharomyces and enzymatically converted to acetoin and 3-hydroxy-2-pentanone, respectively. Purification of a highly enriched diacetyl reductase fraction from Saccharomyces cerevisiae in conjunction with mass spectrometry identified Old Yellow Enzyme (Oye) as an enzyme capable of catalyzing VDK reduction. Kinetic analysis of recombinant Oye1p, Oye2p and Oye3p isoforms confirmed that all three isoforms reduced diacetyl and 2,3-pentanedione in an NADPH-dependent reaction. Transcriptomic analysis of S. cerevisiae (ale) and S. pastorianus (lager) yeast during industrial fermentations showed that the transcripts for OYE1, OYE2 , arabinose dehydrogenase ( ARA1) , α-acetolactate synthase ( ILV2 ) and α-acetohydroxyacid reductoisomerase ( ILV5 ) were differentially regulated in a manner that correlated with changes in extracellular levels of VDKs. These studies provide insights into the mechanism for reducing VDKs and decreasing maturation times of beer which are of commercial importance.
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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