European case studies supporting the derivation of natural background levels and groundwater threshold values for the protection of dependent ecosystems and human health

The EU Water Framework and Groundwater directives stipulate that EU member states have to assess groundwater chemical status by the use of groundwater threshold values derived for the protection of dependent ecosystems and human health. This paper presents a synthesis of main results of 14 European case studies evaluating a methodology for derivation of natural background levels (NBLs) and groundwater threshold values (TVs) proposed by the EU research project "BRIDGE". The 14 investigated groundwater bodies were selected to represent as many aquifer types, climate settings and European ecoregions as possible within the project group that included partners from 17 EU countries. The selected case study sites include transboundary groundwater bodies, EU Pilot River Basins and other important groundwater systems. Some are known to interact with associated ecosystems, while others do not. The proposed method derives groundwater threshold values based on environmental objectives for dependent ecosystems or groundwater "itself" using relevant reference criteria such as natural background levels, environmental quality standards and drinking water standards. Derived groundwater threshold values for dissolved Cl and As applying drinking water standards as examples of reference values, are compared for all 14 case studies. Additionally, more detailed analyses are conducted for the Odense Pilot River Basin and the Vouga River Basin, where groundwater threshold values for N and P and Cl, As, Cd, Ni, Pb, and Zn, respectively, are derived based on environmental objectives and quality standards for groundwater dependent ecosystems. Results demonstrate that the proposed methodology is operational and may be used to protect human health and the environment. Further they show that groundwater threshold values derived from environmental objectives and environmental quality standards for dependent ecosystems in some cases may be significantly lower than drinking water standards, e.g. for nitrate.     

Determinants of plasma PFOA and PFOS levels among 652 Danish men

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of industrial and consumer products and have been detected worldwide in human blood. The sources for human exposure are not well described, but dietary intake is suggested as an important source. In this study of 652 Danish men from the Diet, Cancer and Health cohort, we examined intake of 10 major dietary groups, tap water drinks, alcohol consumption, cooking method, geographical area, age, smoking status, and BMI as potential determinants of PFOA and PFOS plasma levels. Living in the Aarhus area was associated with higher PFOA and PFOS plasma levels compared with living in the Copenhagen area, and never smokers had higher levels than current smokers. Frying as compared with other cooking methods was a determinant of PFOA and PFOS levels. BMI and alcohol consumption were inversely associated with both compounds. Among the dietary groups, only intake of eggs was significantly positively associated with PFOS plasma levels. In future studies, PFOA and PFOS levels in air, dust and water samples should be measured to elucidate further the sources of exposure; exposure through diet needs to be studied in greater detail. Our finding of a higher body burden of PFOA and PFOS among never smokers also warrants further evaluation.     

Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands

The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives, (2R)- and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR ligands. Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1.     

Personality, anxiety, and muscle tension as determinants of response stereotypy.

"The stereotypy and bias with which Ss used the number series 1-11 in a pseudo-ESP experiment was determined under three experimental conditions: (a) experimentally induced anxiety, (b) experimentally induced muscular tension, and (c) a control condition." Ss scoring in the highest and lowest quartile of the MMPI psychasthenia scale were used. "Under the control condition, the high group was found to be more stereotyped and predictable in their use of the number responses, but under the anxiety and muscle tension conditions this relationship was reversed." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

1-Indanone and 1,3-indandione Derivatives as Ligands for Misfolded α-Synuclein Aggregates

The development of imaging agents for in vivo detection of alpha-synuclein (α-syn) pathologies faces several challenges. A major gap in the field is the lack of diverse molecular scaffolds with high affinity and selectivity to α-syn fibrils for in vitro screening assays. Better in vitro scaffolds can instruct the discovery of better in vivo agents. We report the rational design, synthesis, and in vitro evaluation of a series of novel 1-indanone and 1,3-indandione derivatives from a Structure-Activity Relationship (SAR) study centered on some existing α-syn fibril binding ligands. Our results from fibril saturation binding experiments show that two of the lead candidates compounds 8 and 32 bind α-syn fibrils with binding constants (K_d) of 9.0 and 18.8 nM, respectively, and selectivity of greater than 10× for α-syn fibrils compared with amyloid-β (Aβ) and tau fibrils. Our results demonstrate that the lead ligands avidly label all forms of α-syn on PD brain tissue sections, but only the dense core of senile plaques in AD brain tissue, respectively. These results are corroborated by ligand-antibody colocalization data from Syn211, which shows immunoreactivity toward all forms of α-syn aggregates, and Syn303, which displays preferential reactivity toward mature Lewy pathology. Our results reveal that 1-indanone derivatives have desirable properties for the biological evaluation of α-synucleinopathies.