The Cytotoxicity and Mode of Action of 2,3,4-Trisubstituted Pyrroles and Related Derivatives in Human Tmolt4 Leukemia Cells

4-Carbechoxy-l-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybcnzoyl)-3-(4-methoxyphcnyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g. human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase a, RNA polymerases, nucleoside kinase and ribonucleoside reductase

85Peg A: which age for a low metallicity solar like star?

We explore the possible evolutionary status of the primary component of the binary 85 Pegasi, listed as a target for asteroseismic observations by the MOST satellite. In spite of the assessed `subdwarf' status, and of the accurate distance determination from the Hipparcos data, the uncertainties in the metallicity and age, coupled with the uncertainty in the theoretical models, lead to a range of predictions on the oscillation frequency spectrum. Nevertheless, the determination of the ratio between the small separation in frequency modes, and the large separation as suggested by Roxburgh (2004), provides a very good measure of the star age, quite independent of the metallicity in the assumed uncertainty range. In this range, the constraint on the dynamical mass and the further constraint provided by the assumption that the maximum age is 14 Gyr limit the mass of 85PegA to the range from 0.75 to 0.82Msun. This difference of a few hundreths of solar masses leads to well detectable differences both in the evolutionary stage (age) and in the asteroseismic properties. We show that the age determination which will be possible through the asteroseismic measurements for this star is independent either from the convection model adopted or from the microscopic metal diffusion. The latter conclusion is strengthened by the fact that, although metal diffusion is still described in an approximate way, recent observations suggest that the real stars suffer a smaller metal sedimentation with respect to the models.Comment: accepted for publication in the MNRA

Uncovering Ecosystem Service Bundles through Social Preferences

Ecosystem service assessments have increasingly been used to support environmental management policies, mainly based on biophysical and economic indicators. However, few studies have coped with the social-cultural dimension of ecosystem services, despite being considered a research priority. We examined how ecosystem service bundles and trade-offs emerge from diverging social preferences toward ecosystem services delivered by various types of ecosystems in Spain. We conducted 3,379 direct face-to-face questionnaires in eight different case study sites from 2007 to 2011. Overall, 90.5% of the sampled population recognized the ecosystem’s capacity to deliver services. Formal studies, environmental behavior, and gender variables influenced the probability of people recognizing the ecosystem’s capacity to provide services. The ecosystem services most frequently perceived by people were regulating services; of those, air purification held the greatest importance. However, statistical analysis showed that socio-cultural factors and the conservation management strategy of ecosystems (i.e., National Park, Natural Park, or a non-protected area) have an effect on social preferences toward ecosystem services. Ecosystem service trade-offs and bundles were identified by analyzing social preferences through multivariate analysis (redundancy analysis and hierarchical cluster analysis). We found a clear trade-off among provisioning services (and recreational hunting) versus regulating services and almost all cultural services. We identified three ecosystem service bundles associated with the conservation management strategy and the rural-urban gradient. We conclude that socio-cultural preferences toward ecosystem services can serve as a tool to identify relevant services for people, the factors underlying these social preferences, and emerging ecosystem service bundles and trade-offs

Broad-scale patterns of body size in squamate reptiles of Europe and North America

Aim To document geographical interspecific patterns of body size of European and North American squamate reptile assemblages and explore the relationship between body size patterns and environmental gradients. Location North America and western Europe. Methods We processed distribution maps for native species of squamate reptiles to document interspecific spatial variation of body size at a grain size of 110 x 110 km. We also examined seven environmental variables linked to four hypotheses possibly influencing body size gradients. We used simple and multiple regression, evaluated using information theory, to identify the set of models best supported by the data. Results Europe is characterized by clear latitudinal trends in body size, whereas geographical variation in body size in North America is complex. There is a consistent association of mean body size with measures of ambient energy in both regions, although lizards increase in size northwards whereas snakes show the opposite pattern. Our best models accounted for almost 60% of the variation in body size of lizards and snakes within Europe, but the proportions of variance explained in North America were less than 20%. Main conclusions Although body size influences the energy balance of thermoregulating ectotherms, inconsistent biogeographical patterns and contrasting associations with energy in lizards and snakes suggest that no single mechanism can explain variation of reptile body size in the northern temperate zone