Mercapturic acids of acrylamide and glycidamide as biomarkers of the internal exposure to acrylamide in the general population

Acrylamide (AA), a widely used industrial monomer which is categorised to be carcinogenic, was found to be generated in starch-containing foods during the heating process. This discovery has caused reasonable concern about possible health risks to humans due to dietary acrylamide uptake. In order to gain more information on human metabolism of acrylamide and to contribute to the assessment of the human carcinogenic risk due to AA uptake we measured the mercapturic acid of AA and its epoxide glycidamide (GA) i.e. N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) in human urine. The relation between AAMA and GAMA is important in this context because GA is thought to be the ultimate carcinogenic metabolite of AA.The median levels in smokers (n = 13) were found to be about four times higher than in non-smokers (n = 16) with median levels of 127 μg/l versus 29 μg/l for AAMA and 19 μg/l versus 5 μg/l for GAMA. Therefore cigarette smoke proved to be an important source of acrylamide exposure. The level of AAMA in the occupationally non-exposed collective (n = 29) ranged from 3 to 338 μg/l, the level of GAMA from <LOD to 45 μg/l. The ratio of GAMA:AAMA varied from 0.03 to 0.53, median was 0.16 which is in reasonable agreement with results of different studies on rats. Thus the metabolic conversion of acrylamide to its genotoxic epoxide glycidamide seems to occur to a comparable extent in rats and humans. Consequently, risk estimations by various authorities based on experimental data obtained in rats are supported by our findings. Besides we also measured the haemoglobin adducts of AA and GA in the blood of 26 participants. From these results compared to the mercapturic acids, we deduce a steady state for AA uptake, and we demonstrate a higher reactivity of GA in comparison to AA towards haemoglobin compared to glutathione in humans.     

Suitability of E-tongue Sensors to Assess Taste-Masking of Pediatric Liquids by Different Beverages Considering Their Physico-chemical Properties

Manipulation of liquid oral drugs by mixing them into foodstuff is a common procedure for taste-masking of OTC pharmaceuticals when administered to children. However, the taste-masking capability of such application media is not systematically evaluated, and recommendations for suitable media are hardly published. In this study, a sensor array of commercially available and self-developed electronic tongue sensors was employed to assess the taste-masking efficiency of eight different beverages (tap water, apple juice, carrot juice, fennel tea, fruit tea, milk, cocoa, and Alete meal to drink) on the OTC pharmaceuticals Ambroxol-ratiopharm®, Cetirizin AL, and Laxoberal® by multivariate data analysis. The Euclidean distances between each pure application medium and its corresponding drug mixture were used as an indicator for the taste-masking efficiency and correlated to the physico-chemical properties of the beverages. Thus, the pH value, the viscosity, as well as the fat and sugar content of the beverages were included, whereas only the viscosity appeared to be insignificant in all cases. The sugar content as well as the fat content and pH value emerged to be a significant variable in taste-masking efficiency for some of the tested drug products. It was shown that the applied electronic tongue sensors were capable to demonstrate the impact of the physico-chemical properties of the application media on their taste-masking capacity regardless of their non-selectivity towards these characteristics.     

Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagA

Helicobacter pylori is a paradigm of persistent pathogens and major risk factor for developing severe diseases including adenocarcinoma in the human stomach. An important bacterial factor linked to gastric disease progression is the cag pathogenicity island‐encoded type‐IV secretion system (T4SS) effector protein CagA. Translocated CagA undergoes tyrosine phosphorylation at EPIYA‐motifs and then activates or inactivates multiple host signaling proteins in a phosphorylation‐dependent and phosphorylation‐independent fashion. In this way, intracellular CagA acts as a ‘masterkey’ or ‘picklock’, which evolved during evolution to hijack key host cell signal transduction functions. Crucial targets of CagA represent a variety of serine/threonine and tyrosine kinases, which control major checkpoints of eukaryotic signaling. Here we review the signal transmission by translocated CagA on multiple receptor kinases (c‐Met and EGFR) and non‐receptor kinases (Src, Abl, Csk, aPKC, Par1, PI3K, Akt, FAK, GSK‐3, JAK, PAK1, PAK2 and MAP kinases), manipulating a selection of fundamental processes in the human gastric epithelium such as cell adhesion, polarity, proliferation, motility, receptor endocytosis, cytoskeletal rearrangements, apoptosis, inflammation and cell cycle progression. This enormous complexity generates a highly remarkable and puzzling scenario during H. pylori infection. The contribution of these signaling pathways to bacterial survival, persistence and gastric pathogenesis is discussed.     

Detection of unusual carotenoid esters in fresh mango (Mangifera indica L. cv. 'Kent')

The carotenoid pattern of mango cv. 'Kent' was investigated by LC-(APcI)MS analyses. In solvent extracts from the mesocarp an unusual carotenoid ester was identified as violaxanthin dibutyrate. For unequivocal identification of butyric acid by an independent method, total lipids were isolated by solvent extraction from the fruit flesh and analyzed by GC after saponification and subsequent methylation. Thus, evidence of butyric acid (1.6 area%) was provided. To the best of our knowledge, this is the first report on a xanthophyll dibutyrate in plants. Additionally, further carotenoid peaks were tentatively assigned to 9-cis-violaxanthin and neochrom or luteoxanthin, respectively, by their UV/vis and MS data of the saponified extracts.     

Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis

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Elevation,Topography, and Edge Effects Drive Functional Composition of Woody Plant Species in Tropical Montane Forests

Tropical montane forests comprise heterogeneous environments along natural gradients of topography and elevation. Human‐induced edge effects further increase the environmental heterogeneity in these forests. The simultaneous effects of natural and human‐induced gradients on the functional diversity of plant leaf traits are poorly understood. In a tropical montane forest in Bolivia, we studied environmental gradients associated with elevation (from 1900 m to 2500 m asl), topography (ridge and gorge), and edge effects (forest edge vs. forest interior), and their relationship with leaf traits and resource‐use strategies. First, we investigated associations of environmental conditions (soil properties and microclimate) with six leaf traits, measured on 119 woody plant species. Second, we evaluated changes in functional composition with community‐weighted means and functional structure with multidimensional functional diversity indices (FRic, FEve and FDiv). We found significant associations between leaf traits and soil properties in accordance with the trade‐off between acquisition and conservation of resources. Functional composition of leaf traits shifted from the dominance of acquisitive species in habitats at low altitudes, gorges, and forest interior to the dominance of conservative species in habitats at high altitudes, ridges, and forest edges. Functional structure was only weakly associated with the environmental gradients. Natural and human‐induced environmental gradients, especially soil properties, are important for driving leaf traits and resource‐use strategies of woody plants. Nevertheless, weak associations between functional structure and environmental gradients suggest a high redundancy of functional leaf traits in this tropical montane forest.     

Aerobic and anaerobic nitrogen transformation processes in N2-fixing cyanobacterial aggregates

Colonies of N₂-fixing cyanobacteria are key players in supplying new nitrogen to the ocean, but the biological fate of this fixed nitrogen remains poorly constrained. Here, we report on aerobic and anaerobic microbial nitrogen transformation processes that co-occur within millimetre-sized cyanobacterial aggregates (Nodularia spumigena) collected in aerated surface waters in the Baltic Sea. Microelectrode profiles showed steep oxygen gradients inside the aggregates and the potential for nitrous oxide production in the aggregates'' anoxic centres. ¹⁵N-isotope labelling experiments and nutrient analyses revealed that N₂ fixation, ammonification, nitrification, nitrate reduction to ammonium, denitrification and possibly anaerobic ammonium oxidation (anammox) can co-occur within these consortia. Thus, N. spumigena aggregates are potential sites of nitrogen gain, recycling and loss. Rates of nitrate reduction to ammonium and N₂ were limited by low internal nitrification rates and low concentrations of nitrate in the ambient water. Presumably, patterns of N-transformation processes similar to those observed in this study arise also in other phytoplankton colonies, marine snow and fecal pellets. Anoxic microniches, as a pre-condition for anaerobic nitrogen transformations, may occur within large aggregates (⩾1 mm) even when suspended in fully oxygenated waters, whereas anoxia in small aggregates (<1 to ⩾0.1 mm) may only arise in low-oxygenated waters (⩽25 μM). We propose that the net effect of aggregates on nitrogen loss is negligible in NO₃⁻-depleted, fully oxygenated (surface) waters. In NO₃⁻-enriched (>1.5 μM), O₂-depleted water layers, for example, in the chemocline of the Baltic Sea or the oceanic mesopelagic zone, aggregates may promote N-recycling and -loss processes.     

Quantitative DNA Analyses for Airborne Birch Pollen

Birch trees produce large amounts of highly allergenic pollen grains that are distributed by wind and impact human health by causing seasonal hay fever, pollen-related asthma, and other allergic diseases. Traditionally, pollen forecasts are based on conventional microscopic counting techniques that are labor-intensive and limited in the reliable identification of species. Molecular biological techniques provide an alternative approach that is less labor-intensive and enables identification of any species by its genetic fingerprint. A particularly promising method is quantitative Real-Time polymerase chain reaction (qPCR), which can be used to determine the number of DNA copies and thus pollen grains in air filter samples. During the birch pollination season in 2010 in Mainz, Germany, we collected air filter samples of fine (<3 μm) and coarse air particulate matter. These were analyzed by qPCR using two different primer pairs: one for a single-copy gene (BP8) and the other for a multi-copy gene (ITS). The BP8 gene was better suitable for reliable qPCR results, and the qPCR results obtained for coarse particulate matter were well correlated with the birch pollen forecasting results of the regional air quality model COSMO-ART. As expected due to the size of birch pollen grains (~23 μm), the concentration of DNA in fine particulate matter was lower than in the coarse particle fraction. For the ITS region the factor was 64, while for the single-copy gene BP8 only 51. The possible presence of so-called sub-pollen particles in the fine particle fraction is, however, interesting even in low concentrations. These particles are known to be highly allergenic, reach deep into airways and cause often severe health problems. In conclusion, the results of this exploratory study open up the possibility of predicting and quantifying the pollen concentration in the atmosphere more precisely in the future.