40 research outputs found
A Toxicogenomics Approach to Identify New Plausible Epigenetic Mechanisms of Ochratoxin A Carcinogenicity in Rat
Ochratoxin A (OTA) is a mycotoxin occurring naturally in a wide range of food commodities. In animals, it has been shown to cause a variety of adverse effects, nephrocarcinogenicity being the most prominent. Because of its high toxic potency and the continuous exposure of the human population, OTA has raised public health concerns. There is significant debate on how to use the rat carcinogenicity data to assess the potential risk to humans. In this context, the question of the mechanism of action of OTA appears of key importance and was studied through the application of a toxicogenomics approach. Male Fischer rats were fed OTA for up to 2 years. Renal tumors were discovered during the last 6 months of the study. The total tumor incidence reached 25% at the end of the study. Gene expression profile was analyzed in groups of animals taken in intervals from 7 days to 12 months. Tissue-specific responses were observed in kidney versus liver. For selected genes, microarray data were confirmed at both mRNA and protein levels. In kidney, several genes known as markers of kidney injury and cell regeneration were significantly modulated by OTA. The expression of genes known to be involved in DNA synthesis and repair, or genes induced as a result of DNA damage, was only marginally modulated. Very little or no effect was found amongst genes associated with apoptosis. Alterations of gene expression indicating effects on calcium homeostasis and a disruption of pathways regulated by the transcription factors hepatocyte nuclear factor 4 alpha (HNF4α) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were observed in the kidney but not in the liver. Previous data have suggested that a reduction in HNF4α may be associated with nephrocarcinogenicity. Many Nrf2-regulated genes are involved in chemical detoxication and antioxidant defense. The depletion of these genes is likely to impair the defense potential of the cells, resulting in chronic elevation of oxidative stress in the kidney. The inhibition of defense mechanism appears as a highly plausible new mechanism, which could contribute to OTA carcinogenicit
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Exploring electronic effects on the partitioning of actinides(III) from lanthanides(III) using functionalised bis-triazinyl phenanthroline ligands
The first examples of 4,7-disubstituted 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzo-triazin-3-yl)-1,10- phenanthroline (CyMe4 -BTPhen) ligands are reported herein. Evaluating the kinetics, selectivity and stoichiometry of actinide(III) and lanthanide(III) radiotracer extractions has provided a mechanistic insight into the extraction process. For the first time,
it has been demonstrated that metal ion extraction kinetics can be modulated by backbone functionalisation and a promising new CHON compliant candidate ligand with enhanced metal ion extraction kinetics has been identified. The effects of 4,7- functionalisation on the equilibrium metal ion distribution ratios are far more pronounced than those of 5,6-functionalisation. The
complexation of Cm(III) with two of the functionalised ligands was investigated by TRLFS and, at equilibrium, species of 1:2 [M:L] stoichiometry were observed exclusively. A direct correlation between the ELUMO-EHOMO energy gap and metal ion extraction potential is reported, with DFT studies reaffirming experimental findings
Towards a Framework for Understanding Fairtrade Purchase Intention in the Mainstream Environment of Supermarkets
© 2014, Springer Science+Business Media Dordrecht. Despite growing interest in ethical consumer behaviour research, ambiguity remains regarding what motivates consumers to purchase ethical products. While researchers largely attribute the growth of ethical consumerism to an increase in ethical consumer concerns and motivations, widened distribution (mainstreaming) of ethical products, such as fairtrade, questions these assumptions. A model that integrates both individual and societal values into the theory of planned behaviour is presented and empirically tested to challenge the assumption that ethical consumption is driven by ethical considerations alone. Using data sourced from fairtrade shoppers across the UK, structural equation modelling suggests that fairtrade purchase intention is driven by both societal and self-interest values. This dual value pathway helps address conceptual limitations inherent in the underlying assumptions of existing ethical purchasing behaviour m odels and helps advance understanding of consumers’ motivation to purchase ethical products
A single-cell survey of the small intestinal epithelium
Intestinal epithelial cells (IECs) absorb nutrients, respond to microbes, provide barrier function and help coordinate immune responses. We profiled 53,193 individual epithelial cells from mouse small intestine and organoids, and characterized novel subtypes and their gene signatures. We showed unexpected diversity of hormone-secreting enteroendocrine cells and constructed their novel taxonomy. We distinguished between two tuft cell subtypes, one of which expresses the epithelial cytokine TSLP and CD45 (Ptprc), the pan-immune marker not previously associated with non-hematopoietic cells. We also characterized how cell-intrinsic states and cell proportions respond to bacterial and helminth infections. Salmonella infection caused an increase in Paneth cells and enterocytes abundance, and broad activation of an antimicrobial program. In contrast, Heligmosomoides polygyrus caused an expansion of goblet and tuft cell populations. Our survey highlights new markers and programs, associates sensory molecules to cell types, and uncovers principles of gut homeostasis and response to pathogens
Symposium swissYPG 2011 "La Pharmacie en mutation"
Comme en 2009, le groupe des jeunes pharma- ciens suisses (swissYPG) organise cette année un nouveau symposium de formation et de ré- flexion à destination des jeunes pharmaciennes et pharmaciens suisses. Ce dernier aura lieu à Interlaken le 30 novembre 2011, dans le cadre du 1er congrès suisse des pharmaciens
Symposium swissYPG 2011 "Die Apotheke im Wandel"
Wie im Jahre 2009 organisiert die swiss Young Pharmacists Group (swissYPG) in diesem Jahr erneut ein interessantes Symposium für junge Schweizer Apothekerinnen und Apotheker. Das Symposium wird im Rahmen des 1. Schweizerischen Apothekerkongresses, am 30. November 2011 in Interlaken stattfinden
Modelling the Marangoni convection in laser heat treatment
Epitaxial Laser Metal Forming (E-LMF) consists in impinging a jet of
metallic powder onto a molten pool formed by controlled laser heating and
thereby, generating epitaxially a single crystal deposit onto the damaged
component. This new technique aims to be used for the repair and reshape
single crystal gas turbine components. Because of the very localised melting
pool, the high temperature gradients produced during the process must be
carefully controlled in order to avoid both the columnar-to-equiaxed
transition (CET) and the appearance of hot tears. To this end, heat flow
modelling is required to establish the relationship between process
parameters such as laser power, beam diameter and scanning speed, and the
local solidification conditions. When modelling the heat transfer within the
sample, it is necessary to include the liquid flow pattern generated by the
surface tension driven convection known as the Marangoni effect. Indeed, the
fluid flow in the liquid pool dictates the shape of the traces as shown by
the measurements carried out at EPF-Lausanne in re-melting experiments. A
three dimensional (3D) model is implemented in the finite element software
calcosoft in order to model the
development of the fluid convection within the liquid pool. It is shown that
the velocities due to natural convection are of the order of 1 mm/sec
whereas Marangoni convection produces velocities of the order of 1 m/sec.
Moreover, at low scanning speeds, the liquid pool becomes larger than the
beam diameter and the development of Marangoni eddies leads to a widening
and deepening of the pool. The local solidification conditions such as the
thermal gradient and the solidification speed can be extracted at both the
solidus and liquidus temperatures to assess the risk of CET and hot
cracking