A Comparative Structural Bioinformatics Analysis of the Insulin Receptor Family Ectodomain Based on Phylogenetic Information

The insulin receptor (IR), the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor-related receptor (IRR) are covalently-linked homodimers made up of several structural domains. The molecular mechanism of ligand binding to the ectodomain of these receptors and the resulting activation of their tyrosine kinase domain is still not well understood. We have carried out an amino acid residue conservation analysis in order to reconstruct the phylogeny of the IR Family. We have confirmed the location of ligand binding site 1 of the IGF1R and IR. Importantly, we have also predicted the likely location of the insulin binding site 2 on the surface of the fibronectin type III domains of the IR. An evolutionary conserved surface on the second leucine-rich domain that may interact with the ligand could not be detected. We suggest a possible mechanical trigger of the activation of the IR that involves a slight ‘twist’ rotation of the last two fibronectin type III domains in order to face the likely location of insulin. Finally, a strong selective pressure was found amongst the IRR orthologous sequences, suggesting that this orphan receptor has a yet unknown physiological role which may be conserved from amphibians to mammals

Chalcogen-centered spirocyclic mixed-metal carbonyl complexes: Synthesis and molecular structures of (CO)(8)(mu-PCy2)Re-2(mu(4)-E)Fe-2(mu-ER)(CO)(6) and [(CO)(8)(mu-PCy2)Re-2(mu(4)-E)Fe-2(CO)(6)](2)(mu(4)-E-2) (E = S, Se, Te; R organic residue)

When NEt4[Re-2(mu-PCy2)(CO)(8)] (1) was reacted with Fe-2(mu-E-2)(CO)(6) (E = S, Se, TO in THF, the salts NEt4[(CO)(8)(mu-PCy2)Re-2(mu-E)Fe-2(mu-E)(CO)(6)] (E = S (2a), Se (2b), Te (2c)) were formed. Their spirocyclic anions were trapped with MeI, giving the spirocyclic complexes (CO)(8)(mu-PCy2)Re-2(mu(4)-E)Fe-2(mu-EMe)(CO)(6) (E = S (3a), Se (3b), Te (3c)). Their molecular structures were confirmed by single-crystal X-ray analysis. The anions of 2a-c are sensitive to oxidation. On crystallization in the presence of oxygen the corresponding dichalcogenides [(CO)(8)(mu-PCy2)Re-2(mu(4)-E)Fe-2(CO)(6)](2)(mu(4)-E-2) (E = S (4a), Se (4b), Te (4c)) were obtained in good yield. Their molecular structures were confirmed by single-crystal X-ray analysis. 2a was also trapped with CF3COOH, giving (CO)(8)(mu-PCy2)Re-2(mu-S-4)Fe-2(mu-SH)(CO)(6) (5). The latter can be expanded by SH oxidative addition of its mu-SH function to Os-3(CO)(11)(NCMe), giving the mixed-metal carbonyl complex (CO)(8)(mu-PCy2)Re-2(mu(4)-S)Fe-2(CO)(6)(mu(3)-S)Os-3(mu-H)(CO)(11) (6). The framework of 6 could be derived from X-ray diffraction data. However, these data were insufficient for complete solution of the molecular structure, but spectroscopic data and elemental analysis of 6 are in accordance with the proposed molecular structure

Envisioning the future of water in Europe - the SCENES project

The aim of this article is to describe the background and main elements of the SCENES project (Water Scenarios for Europe and Neighbouring States) together with the approach for selecting, constructing and evaluating water scenarios up to 2050. SCENES is a multi-faceted integrated project that aims to address the complex questions about the future of Europe’s water resources. It takes an integrated approach by combining and balancing the many dimensions of Europe’s water futures, including hydrological, ecological, economic, cultural, social, climatic, financial and other dimensions. The project is implemented in three phases. In the first phase (fast-track) largely extant scenarios are selected, and readily available information on drivers and policies information assembled and run through an existing quantitative model of pan-European water availability. In the second phase more refined scenarios are developed at both the pan-European and regional scales, with scenario panels providing ‘enriched’ scenarios. The third phase involves a synthesis of the information and dissemination of the project outputs to external stakeholders and end-users. In the SCENES project an evaluation of the participatory scenario processes is carried out giving us new information on the functioning of the science-policy interface, and on the challenges the European water management may confront in the future

Global water resources affected by human interventionss and climate change

Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future