68 research outputs found
Validation of a novel procedure for quantification of the formation of phosphoramide mustard by individuals treated with cyclophosphamide
Pollen productivity estimates of key European plant taxa for quantitative reconstruction of past vegetation: a review
International audienceInformation on the spatial distribution of past vegetation on local, regional and global scales is increasingly used within climate modelling, nature conservancy and archaeology. It is possible to obtain such information from fossil pollen records in lakes and bogs using the landscape reconstruction algorithm (LRA) and its two models, REVEALS and LOVE. These models assume that reliable pollen productivity estimates (PPEs) are available for the plant taxa involved in the quantitative reconstruc -tions of past vegetation, and that PPEs are constant through time. This paper presents and discusses the PPEs for 15 tree and 18 herb taxa obtained in nine study areas of Europe. Observed differences in PPEs between regions may be explained by methodological issues and environmental variables, of which climate and related factors such as reproduction strategies and growth forms appear to be the most important. An evaluation of the PPEs at hand so far suggests that they can be used in modelling applications and quantitative reconstructions of pastvegetation, provided that consideration of past environmental variability within the region is used to inform selection of PPEs, and bearing in mind that PPEs might have changed through time as a response to climate change. Application of a range of possible PPEs will allow a better evaluation of the results
Exposure assessment of process-related contaminants in food by biomarker monitoring
Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment
Accumulation of calcium and phosphate stimulated by carboxylic antibiotics into mitochondria
Carboxylic ionophores such as nigericin, dianemycin, the monensins and compounds Lilly A 217 or X-537 A, stimulate an electron-transport dependent accumulation of Ca 2+ and phosphate into mitochondria. Ion accumulation is stimulated under conditions of limited Ca 2+ loading imposed by phosphate in the presence of β-hydroxybutyrate. Carboxylic ionophores do not affect divalent ion uptake when β-hydroxybutyrate is replaced for by succinate. They block Ca 2+ and phosphate accumulation when energy is provided from the hydrolysis of ATP, or from the oxidation of glutamate, α-ketoglutarate, pyruvate or glutamate+malate. Nigericin-like antibiotics also transform the indefinite prolongation of state 3 respiration induced by Ca 2+ and phosphate on β-hydroxybutyrate oxidation, into tightly coupled state 3 to 4 transitions. Evidence suggests that electrophoretic Ca 2+ transport occurs in parallel with proton or K + carriers. The anion movements associated to Ca 2+ uptake are most probably driven by the existent ΔpH across the mitochondrial membrane.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44799/1/10863_2005_Article_BF01516075.pd
Trajectories of change in Mediterranean Holocene vegetation through classification of pollen data
© 2017 Springer-Verlag GmbH Germany, part of Springer Nature Quantification of vegetation cover from pollen analysis has been a goal of palynologists since the advent of the method in 1916 by the great Lennart von Post. Pollen-based research projects are becoming increasingly ambitious in scale, and the emergence of spatially extensive open-access datasets, advanced methods and computer power has facilitated sub-continental analysis of Holocene pollen data. This paper presents results of one such study, focussing on the Mediterranean basin. Pollen data from 105 fossil sequences have been extracted from the European Pollen database, harmonised by both taxonomy and chronologies, and subjected to a hierarchical agglomerative clustering method to synthesise the dataset into 16 main groupings. A particular focus of analysis was to describe the common transitions from one group to another to understand pathways of Holocene vegetation change in the Mediterranean. Two pollen-based indices of human impact (OJC: Oleaceae, Juglans, Castanea; API: anthropogenic pollen indicators) have been used to infer the degree of human modification of vegetation within each pollen grouping. Pollen-inferred cluster groups that are interpreted as representing more natural vegetation states show a restricted number of pathways of change. A set of cluster groups were identified that closely resemble anthropogenically-disturbed vegetation, and might be considered anthromes (anthopogenic biomes). These clusters show a very wide set of potential pathways, implying that all potential vegetation communities identified through this analysis have been altered in response to land exploitation and transformation by human societies in combination with other factors, such as climatic change. Future work to explain these ecosystem pathways will require developing complementary datasets from the social sciences and humanities (archaeology and historical sources), along with synthesis of the climatic records from the region
Prevalence of germline pathogenic variants in 22 cancer susceptibility genes in Swedish pediatric cancer patients
Up to 10% of pediatric cancer patients harbor pathogenic germline variants in one or more cancer susceptibility genes. A recent study from the US reported pathogenic variants in 22 out of 60 analyzed autosomal dominant cancer susceptibility genes, implicating 8.5% of pediatric cancer patients. Here we aimed to assess the prevalence of germline pathogenic variants in these 22 genes in a population-based Swedish cohort and to compare the results to those described in other populations. We found pathogenic variants in 10 of the 22 genes covering 3.8% of these patients. The prevalence of TP53 mutations was significantly lower than described in previous studies, which can largely be attributed to differences in tumor diagnosis distributions across the three cohorts. Matched family history for relatives allowed assessment of familial cancer incidence, however, no significant difference in cancer incidence was found in families of children carrying pathogenic variants compared to those who did not
The miR-17-92 MicroRNA Cluster regulates multiple components of the TGF-beta Pathway in neuroblastoma
The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-beta signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-beta signaling cascade as well as direct inhibition of TGF-beta-responsive genes
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