Structure of an agonist-bound human A2A adenosine receptor

Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.     

Variability of cotton (Gossypium hirsutum L.) with regard to earliness

Eighty cotton varieties (Gossypium hirsutum L.) from the collection of VIR (N.I. Vavilov Research Institute of Plant Industry, St. Peterburg, Russia) collection were studied for variability with regard to the duration of their vegetation period. The experiments were carried out in the conditions of the marginal zone of the cotton growing area, that is the city of Krasnodar in the Russian Federation. Thirty-four varieties were studied in 1996–1998, forty-six varieties in 1997–1998. The purpose of this research was to determine the threshold of sensitivity in the varieties of the duration of the period of vegetative growth, which depends upon weather conditions, and to record variations in morphological characters associated with earliness. The data obtained were processed by the method of statusmetry. The mathematical models which were constructed showed the relationship between the criteria for earliness and other morphological and agronomic characters of the plants.     

Endemic species: Contribution to community uniqueness, effect of habitat alteration, and conservation priorities

The biodiversity crisis, particularly dramatic in freshwaters, has prompted further setting of global and regional conservation priorities. Species rarity and endemism are among the most fundamental criteria for establishing these priorities. We studied the patterns of rarity and the role of rare species in community uniqueness using data on freshwater bivalve molluscs (family Unionidae) in Texas. Due to the large size and gradients in landscape and climate, Texas has diverse and distinct unionid communities, including numerous regional and state endemic species. Analysis of the state-wide distribution and abundance of Unionidae allowed us to develop a non-arbitrary method to classify species rarity based on their range size and relative density. Of the 46 Unionidae species currently present in Texas, 65% were classified as rare and very rare, including all state and regional endemics. We found that endemic species were a critical component in defining the uniqueness of unionid communities. Almost all endemics were found exclusively in streams and rivers, where diversity was almost double that of lentic waters. Man’s ongoing alteration of lotic with lentic waterbodies favors common species, and dramatically reduces habitat for endemics, contributing to homogenization of unionid fauna. We identified hotspots of endemism, prioritized species in need of protection, estimated their population size, and recommended changes to their current conservation status.     

Impact of natural and man-made factors on migration of heavy metals in the Ardon River basin (North Ossetia)

Purpose

The main goal of the study was to evaluate biogeochemical effects of particular factors changing the structure of landscapes due to enhanced mass migration and erosion of the outcropping rocks by studying transformation of chemical composition of the draining waters and flood plain soils; chemical composition of the solid and liquid phases of the Ardon River waters; and by assessing ecological consequences and risk of contamination of the area by heavy metals.

Materials and methods

Water, soil, and biota species (plants, algae, and amphibian) were sampled at the plots located up- and downstream the mining and industrial areas of North Ossetia (the Ardon River basin) before and after the mudflow that took place in 2002. The air-dried samples were decomposed in a mixture of mineral acids. Heavy metals were determined by means of AAS with the help of AAS-80 (Hitachi) or AAS-2A (KORTEC) using standard reference materials of hair (CRM 397), plant mixture (SBMT-02), and soil (SRM 2709). Hydrochemical and biochemical analyses were performed with the help of the known methods (Kraynov and Shvets 1992; Burtis et al. 2006).

Results and discussion

The study showed that activity of the Misur Mining Combine and its Ardon-Khost tailings caused a significant local increase of Pb, Cd, Cu, and Zn content in soils, water, and biotic components as compared to the background values. The mudflow of 2002 changed the structure of landscapes and was followed by a considerable transformation of chemical composition of the downstream river waters and floodplain soils, and by invasion of particular hydrophyte species. Algae and amphibian adapted to the changed conditions and indicated both natural and anthropogenic transformation of the environment. A distinct relation between the particle size of the suspended matter in the Ardon River waters and water salinity was discovered.

Conclusions

Therefore, the Unal basin presents a vivid example of modern natural and anthropogenic evolution of Pb-Zn biogeochemical province under conditions of the extreme and dynamic geochemical environment leading to enhanced risks of ecological damage. Algae species demonstrated high adaptive and indicative capacity in case of both the fast natural and man-made impact.

     

Influence of Fucoidans on Hemostatic System

Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested.     

Improvement of Forage Production Sustainability in the Leningrad Region under Climate Change

The increase of probability and depth of weather anomalies, which is important characteristic of climate change process, leads to higher risk of loss of perennial grasses forage yield, rise of price volatility on forage grain market. Increase of sustainability of dairy production supposes development of adapted to new weather conditions technologies of forage production, which are characterized by different investment and current costs. It generates a need of economic evaluation and comparative analysis of technologies taking into account climate change forecast and need of sustainable forage production guarantee. Purpose of the research project is the development of approaches to assessing adaptive technologies in forage production, increasing of dairy farming sustainability to changes in the external environment, including climate change. We assessed changes in forage production technologies in the Leningrad region of Russia, analyzed the implications of these changes for production and financial performance of dairy farming, proposed and tested methods for determination of the optimum harvesting time of perennial grasses. Special attention is paid to the long-term effects of changing the structure of cows＇ diet--shortening the productive use of animals, which reduces the efficiency of dairy herd use and limits the possibility of expanded reproduction. The primary method of the study is the analysis of milk production statistics in the Leningrad region and the Russian Federation. As a result of the study, the necessity to improve the production and investment planning quality, as well as the use of forecasts during planning of dairy production, is grounded.     

Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist

Dopamine modulates movement, cognition, and emotion through activation of dopamine G protein-coupled receptors in the brain. The crystal structure of the human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R-specific antagonist eticlopride reveals important features of the ligand binding pocket and extracellular loops. On the intracellular side of the receptor, a locked conformation of the ionic lock and two distinctly different conformations of intracellular loop 2 are observed. Docking of R-22, a D3R-selective antagonist, reveals an extracellular extension of the eticlopride binding site that comprises a second binding pocket for the aryl amide of R-22, which differs between the highly homologous D2R and D3R. This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications.     

Synthesis, Properties, and Use of Copper-Chelating Amphiphilic Dithiocarbamates as Synergists of Oxidant-Generating Herbicides

The effect of herbicides that act by generating active oxygen species is often mitigated by the enzymes of the Halliwell-Asada oxygen detoxification pathway. Use of compounds interfering with this pathway synergizes herbicides, allowing the killing of weeds at lower herbicide doses. We have used different dithiocarbamate chelators (Dtcs) capable of removing copper from superoxide dismutase, the first enzyme of the pathway, suppressing its action. Dtcs with different hydrophilic-lipophilic properties (sodium salts of ethyl (2-(2-ethoxyethoxy)ethyl)-, butyl (2-(2-ethoxyethoxy)ethyl) -, hexyl (2-(2- ethoxyethoxy)ethyl)-, and dibutyldithiocarbamic acids) were synthesized so that they might penetrate plant cuticles better than sodium diethyldithiocarbamate. Octanol-water distribution ratios and the stabilities of their copper complexes were determined. All Dtcs tested had a high affinity for copper. The Dtcs did not prevent iron-catalyzed Fenton reaction leading to hydroxyl radical productionin vitro. Therefore they would not protect plants from the oxidative damage caused by herbicide, as do compounds that complex iron and thereby prevent the phytotoxic iron-catalyzed Fenton reaction. These amphiphilic compounds show some synergistic activityin vivo, with paraquat as well as lactofen, herbicides that generate active oxygen species by different mechanisms. The results demonstrate that dithiocarbamates have potential as synergists for oxidant-generating herbicides.     

The amount of recycled crust in sources of mantle-derived melts

Plate tectonic processes introduce basaltic crust (as eclogite) into the peridotitic mantle. The proportions of these two sources in mantle melts are poorly understood. Silica-rich melts formed from eclogite react with peridotite, converting it to olivine-free pyroxenite. Partial melts of this hybrid pyroxenite are higher in nickel and silicon but poorer in manganese, calcium, and magnesium than melts of peridotite. Olivine phenocrysts' compositions record these differences and were used to quantify the contributions of pyroxenite-derived melts in mid-ocean ridge basalts (10 to 30%), ocean island and continental basalts (many >60%), and komatiites (20 to 30%). These results imply involvement of 2 to 20% (up to 28%) of recycled crust in mantle melting.