MECHANISMS OF SPECIES DIFFERENCES IN BRAIN ACETYLCHOLINESTERASE SENSITIVITY TO ORGANOPHOSPHATE INHIBITION

In vitro incubation of acetylcholinesterase from brain tissue of several species with organophosphate compounds indicated that the concentrations required to inhibit 50% of acetylcholinesterase activity (IC(,50)) differed from species to species for the same compound (Murphy, et al., 1968; Andersen, et al., 1972, 1977 and 1978).^ The hypothesis that non-specific binding proteins (Lauwerys and Murphy, 1969a,b) exerts a protective effect on acetylcholinesterase, and thus cause the differences observed in IC(,50) studies was tested by a ('3)H-DFP binding experiment. It was found that differences in the amount of non-specific binding protein cannot explain the observed differences observed in IC(,50) studies.^ An alternative hypothesis, that acetylcholinesterase from different species have different affinities for binding and/or different rates of phosphorylation by organophosphate insecticides was tested by determining the apparent affinity constant (k(,a)) and apparent rate of phosphorylation (k(,p)). Kinetic studies indicated that acetylcholinesterases from different species have different sensitivities to inhibition by organophosphate insecticides, and the differences are due to different affinities for binding and/or different rates of phosphorylation by the same organophosphate compound.^ Studies of the spontaneous reactivation of acetylcholinesterase after inhibition by organophosphate insecticides also indicated that acetylcholinesterases from different species have different rates and extents of spontaneous reactivation. This further substantiates the hypothesis that acetylcholinesterases from different species have different kinetic characteristics with respect to organophosphate insecticides inhibition.^ Eleven paraoxon analogs were synthesized for a quantitative structure-activity relationship study. It was found that the electron-withdrawing power ((sigma)) and hydrophobicity ((PARAGR)) of the substituent are important in determining the anti-cholinesterase activity of paraoxon analogs. Thus, predictions of species differences in acetylcholinesterase sensitivities to paraoxon analogs can be made if the physicochemical parameters ((sigma) and (PARAGR)) of the substituents are known.^ In another approach, i.e. enzyme modeling, the sensitivity of rat brain acetylcholinesterase to organophosphate insecticides was used as the independent variable to predict the sensitivities of acetylcholinesterases from other species to the same compound. Regression equations were derived for each species based on nineteen organophosphate insecticides studied. It was found, that in addition to paraoxon analogs, this method is also applicable to other organophosphate compounds with wide variations in structure. Thus, the sensitivities of acetylcholinesterases from other species can also be predicted from the sensitivity of rat brain acetylcholinesterase. ^

Uncertainty analysis of cost effectiveness in a tailored intervention to promote screening for colorectal cancer

Background. Screening for colorectal cancer (CRC) is considered cost effective but screening compliance in the US remains low. There have been very few studies on economic analyses of screening promotion strategies for colorectal cancer. The main aim of the current study is to conduct a cost effectiveness analysis (CEA) and examine the uncertainty involved in the results of the CEA of a tailored intervention to promote screening for CRC among patients of a multispeciality clinic in Houston, TX. ^ Methods. The two intervention arms received a PC based tailored program and web based educational information to promote CRC screening. The incremental cost of implementing a tailored PC based program was compared to the website based education and the status quo of no intervention for each unit of effect after 12 months of delivering the intervention. Uncertainty analysis in the point estimates of cost and effect was conducted using nonparametric bootstrapping. ^ Results. The cost of implementing a web based educational intervention was $36.00 per person and the cost of the tailored PC based interactive intervention was $43.00 per person. The additional cost per person screened for the web-based strategy was $2374 and the effect of the tailored intervention was negative. ^

ATTITUDES AND PRACTICES OF GENETIC COUNSELORS IN PROVIDING PREDICTIVE TESTING TO MINORS AT RISK FOR LI-FRAUMENI SYNDROME

Li- Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome caused by mutations in the TP53 gene that predisposes individuals to a wide variety of cancers, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, and adrenocortical carcinomas. Individuals found to carry germline mutations in TP53 have a 90% lifetime cancer risk, with a 20% chance to develop cancer under the age of 20. Despite the significant risk of childhood cancer, predictive testing for unaffected minors at risk for LFS historically has not been recommended, largely due to the lack of available and effective screening for the types of cancers involved. A recently developed screening protocol suggests an advantage to identifying and screening children at risk for LFS and we therefore hypothesized that this alongside with the availability of new screening modalities may substantiate a shift in recommendations for predictive genetic testing in minors at risk for LFS. We aimed to describe current screening recommendations that genetic counselors provide to this population as well as explore factors that may have influenced genetic counselors attitude and practice in regards to this issue. An online survey was emailed to members of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC). Of an estimated 1000 eligible participants, 172 completed surveys that were analyzed. Genetic counselors in this study were more likely to support predictive genetic testing for this population as the minor aged (p

Faecal pellet production of copepoda collected in water depth up to 30 meters in the eastern Mediterranean Sea in Oktober 2008 during SES_GR2

Mesozooplankton is collected by vertical tows within the Black sea water body mass layer in the NE Aegean, using a WP-2 200 µm net equipped with a large non-filtering cod-end (10 l). Macrozooplankton organisms are removed using a 2000 µm net. A few unsorted animals (approximately 100) are placed inside several glass beaker of 250 ml filled with GF/F or 0.2 µm Nucleopore filtered seawater and with a 100 µm net placed 1 cm above the beaker bottom. Beakers are then placed in an incubator at natural light and maintaining the in situ temperature. After 1 hour pellets are separated from animals and placed in separated flasks and preserved with formalin. Pellets are counted and measured using an inverted microscope. Animals are scanned and counted using an image analysis system. Carbon- Specific faecal pellet production is calculated from a) faecal pellet production, b) individual carbon: Animals are scanned and their body area is measured using an image analysis system. Body volume is then calculated as an ellipsoid using the major and minor axis of an ellipse of same area as the body. Individual carbon is calculated from a carbon- total body volume of organisms (relationship obtained for the Mediterranean Sea by Alcaraz et al. (2003) divided by the total number of individuals scanned and c) faecal pellet carbon: Faecal pellet length and width is measured using an inverted microscope. Faecal pellet volume is calculated from length and width assuming cylindrical shape. Conversion of faecal pellet volume to carbon is done using values obtained in the Mediterranean from: a) faecal pellet density 1,29 g cm**3 (or pg µm**3) from Komar et al. (1981); b) faecal pellet DW/WW=0,23 from Elder and Fowler (1977) and c) faecal pellet C%DW=25,5 Marty et al. (1994).

H.W.M. Olbers measurements of air temperature in Bremen from 1803 to 1822

We rediscovered a temperature time series from Heinrich W. M. Olbers. Heinrich W. M. Olbers measured in Bremen, Sandstrasse 15, in Germany from 1803 to 1821 three times a day (7 am, 1-2 pm and 10 pm) the temperature at his window of his study, which is up to 16 m above the zero marking at the Weserbrücke. The temperature values from 1814 are missing. We got the temperature values from different sources in the Olbers estate. We calculated the daily mean and digitized it in various plots. A very small trend towards cooling is apparent in the data which might be insignificant. But a clear seasonal trend was identifiable: the late winter and the early spring were becoming warmer, while the summer and early autumn became cooler. The average temperature in Bremen was 8.3606 deg C at that time. Additionally we combined the newly discovered Heinrich W. M. Olbers temperature data and the Heinemann and Bätjer data to see whether there are great differences between these two time series. Although the temperatures of Heinrich W. M. Olbers are in general cooler than the Heinemann and Bätjer data they fit together.

Faecal pellet production of copepoda collected in water depth up to 100 meters in the eastern Mediterranean Sea in March and April 2008 during SES_GR1

The SES_UNLUATA_GR1-Mesozooplankton faecal pellet production rates dataset is based on samples taken during March and April 2008 in the Northern Libyan Sea, Southern Aegean Sea and in the North-Eastern Aegean Sea. Mesozooplankton is collected by vertical tows within the 0-100 m layer or within the Black sea water body mass layer in the case of the NE Aegean, using a WP-2 200 µm net equipped with a large non-filtering cod-end (10 l). Macrozooplankton organisms are removed using a 2000 µm net. A few unsorted animals (approximately 100) are placed inside several glass beaker of 250 ml filled with GF/F or 0.2 µm Nucleopore filtered seawater and with a 100 µm net placed 1 cm above the beaker bottom. Beakers are then placed in an incubator at natural light and maintaining the in situ temperature. After 1 hour pellets are separated from animals and placed in separated flasks and preserved with formalin. Pellets and are counted and measured using an inverted microscope. Animals are scanned and counted using an image analysis system. Carbon- Specific faecal pellet production is calculated from a) faecal pellet production, b) individual carbon: Animals are scanned and their body area is measured using an image analysis system. Body volume is then calculated as an ellipsoid using the major and minor axis of an ellipse of same area as the body. Individual carbon is calculated from a carbon- total body volume of organisms (relationship obtained for the Mediterranean Sea by Alcaraz et al. (2003) divided by the total number of individuals scanned and c) faecal pellet carbon: Faecal pellet length and width is measured using an inverted microscope. Faecal pellet volume is calculated from length and width assuming cylindrical shape. Conversion of faecal pellet volume to carbon is done using values obtained in the Mediterranean from: a) faecal pellet density 1,29 g cm**3 (or pg µm**3) from Komar et al. (1981); b) faecal pellet DW/WW=0,23 from Elder and Fowler (1977) and c) faecal pellet C%DW=25,5 Marty et al. (1994).

Faecal pellet production of copepoda collected in water depth up to 20 meters in the eastern Mediterranean Sea in March and April 2008 during SES_GR1

The SES_GR1-Mesozooplankton faecal pellet production rates dataset is based on samples taken during April 2008 in the North-Eastern Aegean Sea. Mesozooplankton is collected by vertical tows within the Black sea water body mass layer in the NE Aegean, using a WP-2 200 µm net equipped with a large non-filtering cod-end (10 l). Macrozooplankton organisms are removed using a 2000 µm net. A few unsorted animals (approximately 100) are placed inside several glass beaker of 250 ml filled with GF/F or 0.2 µm Nucleopore filtered seawater and with a 100 µm net placed 1 cm above the beaker bottom. Beakers are then placed in an incubator at natural light and maintaining the in situ temperature. After 1 hour pellets are separated from animals and placed in separated flasks and preserved with formalin. Pellets are counted and measured using an inverted microscope. Animals are scanned and counted using an image analysis system. Carbon- Specific faecal pellet production is calculated from a) faecal pellet production, b) individual carbon: Animals are scanned and their body area is measured using an image analysis system. Body volume is then calculated as an ellipsoid using the major and minor axis of an ellipse of same area as the body. Individual carbon is calculated from a carbon- total body volume of organisms (relationship obtained for the Mediterranean Sea by Alcaraz et al. (2003) divided by the total number of individuals scanned and c) faecal pellet carbon: Faecal pellet length and width is measured using an inverted microscope. Faecal pellet volume is calculated from length and width assuming cylindrical shape. Conversion of faecal pellet volume to carbon is done using values obtained in the Mediterranean from: a) faecal pellet density 1,29 g cm**3 (or pg µm**3) from Komar et al. (1981); b) faecal pellet DW/WW=0,23 from Elder and Fowler (1977) and c) faecal pellet C%DW=25,5 Marty et al. (1994).

Observations of plankton production in Kiel Bay 1957 to 1975

This data volume presents a series of planktological observations carried out over a 19-year-period in Kiel Bight in the Western Baltic Sea. Three fixed stations were visited at monthly intervals, and the planktion standing stock was investigated in relation to depth and environmental factors, employing a standard observation programme. This consisted in the measurements of temperature, salinity, density, oxygen, phosphorus, seston, protein and chlorophyll a. Additional measurements comprised in the caloric content of seston, particulate organic carbon and nitrogen, as well as dry weight and organic matter of plankton, sampled by vertical hauls of three plankton nets of different mesh size.

A CO2-saving-based methodology to measure the impact of the SUMP in European Cities: Application to the City of Burgos

Urban mobility in Europe is always a responsibility of the municipalities which propose measures to reduce CO2 emissions in terms of mobility aimed at reducing individual private transport (car). The European Commission's Action Plan on Urban Mobility calls for an increase in the take-up of Sustainable Urban Mobility Plans in Europe. SUMPs aim to create a sustainable urban transport system. Europe has got some long term initiatives and has been using some evaluation procedures, many of them through European projects. Nevertheless, the weak point with the SUMPs in Spain, has been the lack of concern about the evaluation and the effectiveness of the measures implemented in a SUMP. For this reason, it is difficult to know exactly whether or not the SUMPs have positively influenced in the modal split of the cities, and its contribution to reduce CO2 levels. The case of the City of Burgos is a very illustrative example as it developed a CiViTAS project during the years 2005-2009, with a total investment of 6M?. The results have been considered as ?very successful? even at European level. The modal split has changed considerably for better, The cost-effectiveness ratio of the SUMP in the city can be measured with the CO2 ton saved, specifically 36 ? per CO2 ton saved, which is fully satisfactory and in line with calculations from other European researchers. Additionally, the authors propose a single formula to measure the effectiveness of the activities developed under the umbrella of a SUMP.

The construction of sexpartite vaults in Europe

Sexpartite vaults constitute one of the most interesting chapters in European Gothic architecture. Originally, the use of the square cross-ribbed vault was limited to relatively small spaces, but when the need arose to cover spaces of considerable size, a new vault with very peculiar characteristics appeared. This new vault was a cross-ribbed vault that was reinforced in the centre by a rib that was parallel to the transverse ribs which effectively divided the vault in half. This configuration breaks the side arch into two fragments, creating a pair of windows on each side. The volumetrics of these vaults is extremely complex and the difficulties involved in their construction perhaps explain why they were abandoned in favour of the simple cross ribbed vault, now with rectangular sections. The existence of the sexpartite vault barely lasted more than fifty years, from the end of the XII century and the beginning of the XIII. Towards the end of the 19th century Viollet-le-Duc gave a succinct explanation of this type of vault. A. Choisy also, later, devotes some pages to the French sexpartite vault; since then, the subject has only been broached in a few references in later studies on Gothic architecture. However, despite its short period of existence, the sexpartite vault spread throughout Europe and was used to build important vaulting. Viollet-le-Duc's sexpartite vault could be considered to be the prototype of them all, while it is true that the studies that we have conducted so far lead us to affirm that there is a wide variety of vaults, with different volumetric spaces and different construction strategies. Therefore, we believe that this chapter of international Gothic deserves further study applying the knowledge and resources that are available today. This paper has been written to explore the most significant European sexpartite vaults. New measurement technology has led to a revolution in research into the history of construction, allowing studies to be conducted that were hitherto impossible. Thorough data collection using total station and photogrammetry has enabled us to identify the stereotomy of the voussoirs, tas-de-charges and keystones, as well as the bonding of the surfaces of the severies. A comparison of the construction techniques employed in the different vaults studied reveals common construction features and aspects that are specific to each country. Thus we are able to establish the relationship between sexpartite vaults in different European countries and their influence on each other.

A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage

Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. Much of our current understanding of checkpoints comes from genetic studies conducted in yeast. In the fission yeast Schizosaccharomyces pombe (Sp), SpRad3 is an essential component of both the DNA damage and DNA replication checkpoints. The SpChk1 and SpCds1 protein kinases function downstream of SpRad3. SpChk1 is an effector of the DNA damage checkpoint and, in the absence of SpCds1, serves an essential function in the DNA replication checkpoint. SpCds1 functions in the DNA replication checkpoint and in the S phase DNA damage checkpoint. Human homologs of both SpRad3 and SpChk1 but not SpCds1 have been identified. Here we report the identification of a human cDNA encoding a protein (designated HuCds1) that shares sequence, structural, and functional similarity to SpCds1. HuCds1 was modified by phosphorylation and activated in response to ionizing radiation. It was also modified in response to hydroxyurea treatment. Functional ATM protein was required for HuCds1 modification after ionizing radiation but not after hydroxyurea treatment. Like its fission yeast counterpart, human Cds1 phosphorylated Cdc25C to promote the binding of 14-3-3 proteins. These findings suggest that the checkpoint function of HuCds1 is conserved in yeast and mammals.

Computer determination of peptide conformations in water: different roads to structure.

Fragments of proteins (short peptides) that "fold" suggest a mechanism of how complete conformational search in protein folding is avoided. We used a computational method to determine structures of two foldable peptides in explicit water: RVEW and CSVTC. The optimization starts from random structures and no experimental constraints are used. In agreement with NMR data, the simulations find a hydrophobic pair (Val/Trp) in REVW. The structure of CSVTC is induced by a surface water that bridges two amide hydrogens, a drive to structure hypothesized by Ben-Naim [Ben-Naim, A. (1990) J. Chem. Phys. 93, 8196-8210] that is largely ignored in studies of folding. Tendency to structure in short peptide chains suggests a mechanism for the formation of short-range nucleation sites in protein folding.

Innovation in the teaching of sustainable development in Europe: the case of ISLE Erasmus Network

Sustainable Development (SD) is one of the most widely used terms during the last years. It is a multidisciplinary concept, which applies mostly to life sciences but is not limited to them. Even though the short survey conducted by the authors revealed that there are only a few cases of Higher Educational Institutes (HEIs) around Europe that provide programs dedicated to SD, it is obvious that there is a constant raise in the need for implementing courses related to SD in existing programs. This paper discusses the case study of I.S.L.E., an Erasmus Academic Network, which aims to use the existing knowledge and tools in the context of teaching sustainable development topics in Universities and HEIs around Europe as a basis, and elaborate further by introducing an innovative approach towards the improvement of teaching SD in HEIs, based on the current needs as they are identified by the actions of the Network.