The Role of Climate in Settlement and Landscape Change in the North Atlantic Islands: An Assessment of Cumulative Deviations in High-Resolution Proxy Climate Records

In order to assess possible contributions of climate change to the human ecology of the North Atlantic islands we evaluate the utility of cumulative deviations from the mean, calculated for the Greenland ice core storm frequency proxy (GISP2 Na⁺) and sea ice proxy (GISP2 chloride excess). Our aim is to identify episodes of unpredictable change in the context of long-term trends of cultural and environmental development. Key changes are identified in the proxy climate records in 975 and 980 ad, 1025 and 1040 ad, 1180 ad, 1425 and 1450 ad, and 1520 and 1525 ad. Some of these changes are consistent with those inferred from new studies of the palaeoecological record of the Faroes. This indicates that the cumulative deviation measure could give greatest prominence to the most important climate changes affecting landscapes and settlement (such as the changes of 1425 and 1450 ad and their immediate aftermath), rather than extreme events, such as great single storms.     

A Statistical Approach for Estimation of Process Flow Data from Production of Chemicals of Fossil Origin (6 pp)

Goal, Scope and Background The life cycles of many products including textiles contain chemicals for which process flow data are not known or are too time consuming to collect. Although each chemical may not contribute significantly to the LCA results of the product, which might justify excluding them, but together their contribution could be significant. Similarly, rough estimates of the process flows for the production of a single chemical may be very uncertain and considered meaningless, while the estimates of the cumulative data of process flows for several chemicals may be less uncertain and be a meaningful contribution to the quality of the LCA results. There are methods for estimation of process flows for different types of products, with varying demands regarding input data and time and with varying accuracy of the results. This work contributes to the available methods, focusing on simple estimations for production of chemical substances. The goal was to create a fast method for estimation of emissions, resource and energy flows (process flows) for the production of chemicals, based on easily available data on the properties of the chemicals. The process flows investigated were limited to those normally associated with process industries and contributing most to depletion of resources, to global warming, acidification, eutrophication and photochemical ozone production, i.e. use of energy, crude oil, coal, natural gas, uranium in ore and emissions of CO2, SOx, NOx, NMVOC, methane, BOD, COD and total N. Toxic substances were excluded, since toxic emissions are substance specific and cannot be included in a generalization. Method Available data for the process flows for the production of chemicals of mainly fossil origin were correlated to properties of chemicals such as amount of carbon in the molecule, heat of formation and average number of chemical reaction steps in the production. The production procedures were found in readily available literature. Up to about six reaction steps were evaluated in the correlation study. The variations in the process flows among the chemicals studied were calculated. Results and Discussion There were weak correlations between average number of chemical reaction steps in the production and energy use, COD measured in water emissions, and SOx and NOx emissions to air. For the remaining properties of chemicals and process flows, there were only weak correlations for share of double bonding in the molecule if only molecules containing double bondings were included. Conclusions The precision in estimation of the process flows increases non-significantly when adding information on the number of reaction steps or share of double bonding for chemicals containing double bonding is added. Recommendations and Outlook It seems reasonable to start with a simple grouping method to estimate the process flows for the production of a chemical of fossil origin. Further investigations might investigate whether there is a correlation between process flows and the costs of chemicals, and further study the correlations between process flows and share of double bonding for chemicals containing double bondings.     

Cyclin D1 regulates p27 stability in B cells

p27^Kip1 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G₁/S transition, and whose activity is, in part, regulated through interactions with D-type cyclins. We have generated the BD1-9 cell line, a BaF3 pro-B cells derivative in which cyclin D1 can be induced rapidly and reversibly by ponasterone A. The induction of cyclin D1 expression leads to a targeted p27^Kip1 accumulation in both cytoplasmic and nuclear compartments. But, only the p27^Kip1 form phosphorylated on serine 10 (pSer10-p27^Kip1) accumulates in BD1-9 cells. We found that the binding of cyclin D1 and pSer10-p27^Kip1 prevents p27^Kip1 degradation by the cytoplasmic Kip1 ubiquitylation-promoting complex (KPC) proteosomic pathway. Importantly, the nuclear CDK2 activity which is crucial for G₁/S transition is not altered by p27^Kip1 increase. Using siRNA techniques, we revealed that p27^Kip1 inhibition does not affect the distribution of BD1-9 cells in the different phases of the cell cycle. Our study demonstrates that aberrant cyclin D1 expression acts as a p27^Kip1 trap in B lymphocytes but does not induce p27^Kip1 relocation from the nucleus to the cytoplasm and does not modulate the G₁/S transition. Since our cellular model mimics what observed in aggressive lymphomas, our data bring new insights into the understanding of their physiopathology.     

Investigating serum factors promoting erythrocytic growth of Plasmodium falciparum

The elucidation of factors inducing the growth of Plasmodium falciparum can provide critical information about the developmental mechanisms of this parasite and open the way to search for novel targets for malaria chemotherapy. The ability of components of a growth-promoting factor derived from bovine serum and various related substances to sustain growth of P. falciparum was characterized. A simple total lipid fraction (GFS-C) containing non-esterified fatty acids (NEFAs) as essential factors was noted to promote the parasite's growth. Various proteins from a variety of animals were tested, indicating the importance not only of GFS-C, but also of specific proteins, such as bovine and human albumin, in the parasite growth. Several combinations of the NEFAs tested sustained low parasite growth. Among various phospholipids and lysophospholipids tested, lysophosphatidylcholine containing C-18 unsaturated fatty acids was found to sustain the complete development of the parasite in the presence of bovine albumin. Several other lysophospholipids can partially support growth of P. falciparum.     

Crystal structure of the kainate receptor GluR5 ligand-binding core in complex with (S)-glutamate

The X-ray structure of the ligand-binding core of the kainate receptor GluR5 (GluR5-S1S2) in complex with (S)-glutamate was determined to 1.95 A resolution. The overall GluR5-S1S2 structure comprises two domains and is similar to the related AMPA receptor GluR2-S1S2J. (S)-glutamate binds as in GluR2-S1S2J. Distinct features are observed for Ser741, which stabilizes a highly coordinated network of water molecules and forms an interdomain bridge. The GluR5 complex exhibits a high degree of domain closure (26 degrees) relative to apo GluR2-S1S2J. In addition, GluR5-S1S2 forms a novel dimer interface with a different arrangement of the two protomers compared to GluR2-S1S2J.     

Structure of the house dust mite allergen Der f 2: implications for function and molecular basis of IgE cross-reactivity

The X-ray structure of the group 2 major allergen from Dermatophagoides farinae (Der f 2) was determined to 1.83 A resolution. The overall Der f 2 structure comprises a single domain of immunoglobulin fold with two anti-parallel beta-sheets. A large hydrophobic cavity is formed in the interior of Der f 2. Structural comparisons to distantly related proteins suggest a role in lipid binding. Immunoglobulin E (IgE) cross-reactivity between group 2 house dust mite major allergens can be explained by conserved surface areas representing IgE binding epitopes.     

Molecular dynamics study of the metallochaperone Hah1 in its apo and Cu(I)-loaded states: role of the conserved residue M10

Molecular dynamics simulations were performed on both apo and copper forms of the human copper chaperone, Hah1. Wild-type Hah1 and a methionine (M10) to serine mutant were investigated. We have evidenced the central role of residue M10 in stabilizing the hydrophobic core of Hah1 as well as the internal structure of the metal-binding site. When copper(I) is bound, the mobility of Hah1 is reduced whereas mutation of M10 implies a drastic increase of the mobility of apoHah1, stressing the importance of this highly conserved hydrophobic residue for copper sequestration by the apoprotein.     

Structure prediction and molecular simulation of gases diffusion pathways in hydrogenase

Although hydrogen is considered to be one of the most promising future energy sources and the technical aspects involved in using it have advanced considerably, the future supply of hydrogen from renewable sources is still unsolved. The [Fe]- hydrogenase enzymes are highly efficient H(2) catalysts found in ecologically and phylogenetically diverse microorganisms, including the photosynthetic green alga, Chlamydomonas reinhardtii. While these enzymes can occur in several forms, H(2) catalysis takes place at a unique [FeS] prosthetic group or H-cluster, located at the active site. 3D structure of the protein hydA1 hydrogenase from Chlamydomonas reinhardtti was predicted using the MODELER 8v2 software. Conserved region was depicted from the NCBI CDD Search. Template selection was done on the basis NCBI BLAST results. For single template 1FEH was used and for multiple templates 1FEH and 1HFE were used. The result of the Homology modeling was verified by uploading the file to SAVS server. On the basis of the SAVS result 3D structure predicted using single template was chosen for performing molecular simulation. For performing molecular simulation three strategies were used. First the molecular simulation of the protein was performed in solvated box containing bulk water. Then 100 H(2) molecules were randomly inserted in the solvated box and two simulations of 50 and 100 ps were performed. Similarly 100 O(2) molecules were randomly placed in the solvated box and again 50 and 100 ps simulation were performed. Energy minimization was performed before each simulation was performed. Conformations were saved after each simulation. Analysis of the gas diffusion was done on the basis of RMSD, Radius of Gyration and no. of gas molecule/ps plot.