Synthesis and biological activity of anticoagulant heparan sulfate glycopolymers

Heparin has been used as an anticoagulant drug for more than 70 years. The global distribution of contaminated heparin in 2007, which resulted in adverse clinical effects and over 100 deaths, emphasizes the necessity for safer alternatives to animal-sourced heparin. The structural complexity and heterogeneity of animal-sourced heparin not only impedes safe access to these biologically active molecules, but also hinders investigations on the significance of structural constituents at a molecular level. Efficient methods for preparing new synthetic heparins with targeted biological activity are necessary not only to ensure clinical safety, but to optimize derivative design to minimize potential side effects. Low molecular weight heparins have become a reliable alternative to heparin, due to their predictable dosages, long half-lives, and reduced side effects. However, heparin oligosaccharide synthesis is a challenging endeavor due to the necessity for complex protecting group manipulation and stereoselective glycosidic linkage chemistry, which often result in lengthy synthetic routes and low yields. Recently, chemoenzymatic syntheses have produced targeted ultralow molecular weight heparins with high-efficiency, but continue to be restricted by the substrate specificities of enzymes.

To address the need for access to homogeneous, complex glycosaminoglycan structures, we have synthesized novel heparan sulfate glycopolymers with well-defined carbohydrate structures and tunable chain length through ring-opening metathesis polymerization chemistry. These polymers recapitulate the key features of anticoagulant heparan sulfate by displaying the sulfation pattern responsible for heparin’s anticoagulant activity. The use of polymerization chemistry greatly simplifies the synthesis of complex glycosaminoglycan structures, providing a facile method to generate homogeneous macromolecules with tunable biological and chemical properties. Through the use of in vitro chromogenic substrate assays and ex vivo clotting assays, we found that the HS glycopolymers exhibited anticoagulant activity in a sulfation pattern and length-dependent manner. Compared to heparin standards, our short polymers did not display any activity. However, our longer polymers were able to incorporate in vitro and ex vivo characteristics of both low-molecular-weight heparin derivatives and heparin, displaying hybrid anticoagulant properties. These studies emphasize the significance of sulfation pattern specificity in specific carbohydrate-protein interactions, and demonstrate the effectiveness of multivalent molecules in recapitulating the activity of natural polysaccharides.

Temporal and spatial variations in the quality of water in El Gergal Reservior, Seville, Spain

It is often difficult to define ‘water quality’ with any degree of precision. One approach is that suggested by Battarbee (1997) and is based on the extent to which individual lakes have changed compared with their natural ‘baseline’ status. Defining the base-line status of artificial lakes and reservoirs however, is, very difficult. In ecological terms, the definition of quality must include some consideration of their functional characteristics and the extent to which these characteristics are self-sustaining. The challenge of managing lakes in a sustainable way is particularly acute in semi-arid, Mediterranean countries. Here the quality of the water is strongly influenced by the unpredictability of the rainfall as well as year-to-year variations in the seasonal averages. Wise management requires profound knowledge of how these systems function. Thus a holistic approach must be adopted and the factors influencing the seasonal dynamics of the lakes quantified over a range of spatial and temporal scales. In this article, the authors describe some of the ways in which both long-term and short-term changes in the weather have influenced the seasonal and spatial dynamics of phytoplankton in El Gergal, a water supply reservoir situated in the south of Spain. The quality of the water stored in this reservoir is typically very good but surface blooms of algae commonly appear during warm, calm periods when the water level is low. El Gergal reservoir is managed by the Empresa Municipal de Abastecimiento y Saneamiento (EMASESA) and supplies water for domestic, commercial and industrial use to an area which includes the city of Seville and twelve of its surrounding towns (ca. 1.3 million inhabitants). El Gergal is the last of two reservoirs in a chain of four situated in the Rivera de Huelva basin, a tributary of the Guadalquivir river. It was commissioned by EMASESA in 1979 and since then the company has monitored its main limnological parameters on, at least, a monthly basis and used this information to improve the management of the reservoir. As a consequence of these intensive studies the physical, chemical and biological information acquired during this period makes the El Gergal database one of the most complete in Spain. In this article the authors focus on three ‘weather-related’ effects that have had a significant impact on the composition and distribution of phytoplankton in El Gergal: (i) the changes associated with severe droughts; (ii) the spatial variations produced by short-term changes in the weather; (iii) the impact of water transfers on the seasonal dynamics of the dinoflagellate Ceratium.

Effect of Al(PO3)(3) content on physical, chemical and optical properties of fluorophosphate glasses for 2 mu m application

The effect of Al(PO3)(3) content on physical, chemical and optical properties of fluorophosphate glasses for 2 mu m application, such as thermal stability, chemical durability, surface hardness, absorption spectra and emission spectra, is investigated. With the increment of Al(PO3)(3) content, the thermal stability characterized by the gap of T-g and T,, increases first and then decreases, and reaches the maximum level containing 5 mol% Al(PO3)(3) content. The density and chemical durability decrease monotonously with the introduction of Al(PO3)(3) content increasing, while the refractive index and surface hardness increase. Above properties of fluorophosphate glasses are also compared with fluoride glasses and phosphate glasses. The Judd-Ofelt parameters, absorption and emission cross sections are discussed based on the absorption spectra of Tm-doped glasses. The emission spectra are also measured and the 1.8 mu m fluorescence of the sample is obvious indicating that it is suitable to 2 mu m application. (c) 2008 Elsevier B.V. All rights reserved.

An assessment of chemical contaminants, toxicity and benthic infauna in sediments from the St. Thomas East End Reserves (STEER)

This report contains a chemical and biological characterization of sediments from the St. Thomas East End Reserves (STEER) in St. Thomas, U.S. Virgin Islands (USVI). The STEER Management Plan (published in 2011) identified chemical contaminants and habitat loss as high or very high threats and called for a characterization of chemical contaminants as well as an assessment of their effects on natural resources. The baseline information contained in this report on chemical contaminants, toxicity and benthic infaunal community composition can be used to assess current conditions, as well as the efficacy of future restoration activities. In this phase of the project, 185 chemical contaminants, including a number of organic (e.g., hydrocarbons and pesticides) and inorganic (e.g., metals) compounds, were analyzed from 24 sites in the STEER. Sediments were also analyzed using a series of toxicity bioassays, including amphipod mortality, sea urchin fertilization impairment, and the cytochrome P450 Human Reporter Gene System (HRGS), along with a characterization of the benthic infaunal community. Higher levels of chemical contaminants were found in Mangrove Lagoon and Benner Bay in the western portion of the study area than in the eastern area. The concentrations of polychlorinated biphenyls (PCBs), DDT (dichlorodiphenyltrichloroethane), chlordane, zinc, copper, lead and mercury were above a NOAA sediment quality guideline at one or more sites, indicating impacts may be present in more sensitive species or life stages in the benthic environment. Copper at one site in Benner Bay, however, was above a NOAA guideline indicating that effects on benthic organisms were likely. The antifoulant boat hull ingredient tributyltin, or TBT, was found at the third highest concentration in the history of NOAA’s National Status and Trends (NS&T) Program, which monitors the Nation’s coastal and estuarine waters for chemical contaminants and bioeffects. Unfortunately, there do not appear to be any established sediment quality guidelines for TBT. Results of the bioassays indicated significant sediment toxicity in Mangrove Lagoon and Benner Bay using multiple tests. The benthic infaunal communities in Mangrove Lagoon and Benner Bay appeared severely diminished.

Studies on selected biological parameters off Mithapur (Gujarat)

The biological characteristics off Mithapur, India, indicated fairly high productivity in terms of macrobenthos and phytoplankton pigment concentration. The area sustained low standing stock of zooplankton. The overall biological productivity of plankton and macrobenthos indicated 30-90% reduction from the premonsoon to postmonsoon period. This decline in the standing stock of plankton and benthos was coinciding with the peak fishing season of the area.

Physical, chemical, algal composition and primary production in the four Kisoro minor lakes

The study was conducted between 1998 and 1999. Physical, chemical and biological factors of the water quality characteristics were collected and analysed

Carbon nanostructure-based field-effect transistors for label-free chemical/biological sensors.

Over the past decade, electrical detection of chemical and biological species using novel nanostructure-based devices has attracted significant attention for chemical, genomics, biomedical diagnostics, and drug discovery applications. The use of nanostructured devices in chemical/biological sensors in place of conventional sensing technologies has advantages of high sensitivity, low decreased energy consumption and potentially highly miniaturized integration. Owing to their particular structure, excellent electrical properties and high chemical stability, carbon nanotube and graphene based electrical devices have been widely developed for high performance label-free chemical/biological sensors. Here, we review the latest developments of carbon nanostructure-based transistor sensors in ultrasensitive detection of chemical/biological entities, such as poisonous gases, nucleic acids, proteins and cells.

Relationships between microcystins and environmental parameters in 30 subtropical shallow lakes along the Yangtze River, China

1. A survey of 30 subtropical shallow lakes in the middle and lower reaches of the Yangtze River area in China was conducted during July-September in 2003-2004 to study how environmental and biological variables were associated with the concentration of the cyanobacterial toxin microcystin (MC). 2. Mean MC concentration in seasonally river-connected lakes (SL) was nearly 33 times that in permanently river-connected lakes (RL), and more than six times that in city lakes (NC) and non-urban lakes (NE) which were not connected to the Yangtze River. The highest MC (8.574 mu g L-1) was detected in Dianshan Lake. 3. MC-RR and MC-LR were the primary toxin variants in our data. MC-RR, MC-YR and MC-LR were significantly correlated with Ch1 a, biomass of cyanobacteria, Microcystis and Anabaena, indicating that microcystins were mainly produced by Microcystis and Anabaena sp. in these lakes. 4. Nonlinear interval maxima regression indicated that the relationships of Secchi depth, total nitrogen (TN) : total phosphorus UP) and NH4+ with MC were characterised by negative exponential curves. The relationships between MC and TN, TP, NO3- + NO2- were fitted well with a unimodal curve. 5. Multivariate analyses by principal component and classifying analysis indicated that MC was mainly affected by Microcystis among the biological factors, and was closely related with temperature among physicochernical factors.

Influence of environmental variables on macroinvertebrates in a macrophyte-dominated Chinese lake, with emphasis on the relationships between macrophyte heterogeneity and macroinvertebrate patterns

The benthic community structure in Baoan Lake was examined in relation to lake water physicochemical characteristics and biological parameters. Seventy macroinvertebrate taxa were identified, and mollusks constituted the dominant group and accounted for more than 80% of the total abundance. Assemblages were composed mainly of scrapers (81.5%) and collector-gatherers (roughly 10%). Three plant variables (richness, total cover, and total biomass) were strongly correlated with the faunal gradient (p<0.05). Other predicator variables were Cl-, SiO2, and chemical oxygen demand. Because of the importance of macrophytes in structuring benthic assemblage in this lentic system, the spatial heterogeneity of macrophytes also influenced the pattern of macroinvertebrates. Seven lake regions were uniquely characterized according to primary macrophyte composition and biomass. There were significant differences for macroinvertebrate taxa richness, abundance, and biodiversity among the seven macrophyte regions.

Preparation, Surface Properties and Biological Activity of the Composite of Poly (lactide-co-glycolide) and Bioglass Nanoparticles Surface Grafted with Poly(L-lactide)

SiO2-CaO-P2O5 gel bioglass (BG) nanoparticles with the diameter of 40 nm were synthesized by sol-gel approach. The surface of BG nanoparticles was grafted through the ring-open polymerization of the L-lactide to yield poly (L-lactide) (PLLA) grafted gel particle (PLLA-g-BG). The PLLA-g-BG was further blended with poly(lactide-co-glycolide) (PLGA) to prepare the nanocomposites of PLLA-g-BG/PLGA with the various blend ratios of two phases. PLLA-g-BG accounted 10%, 20% and 40% in the composite, respectively. TGA, ESEM and EDX were used to analyze the graft ratio of PLLA-g-BG, the dispersion of nano-particles and the surface elements of the composites respectively. The rabbit osteoblasts were seeded and cultured on the thin films of composites in vitro. The cell adhesion, spreading and growth of osteoblasts were analyzed with FITC staining, NIH Image J software and MTT assay. The change of cell cycle was monitored by flow cytometry (FCM). The results demonstrated that the Surface modification of BG with PLLA could significantly improve the dispersing of the particles in the matrix of PLGA. The nanocomposite with 20% PLLA-g-BG exhibited superior surface properties, including roughness and plenty of silicon, calcium and phosper, to enhance the adhesion, spreading and proliferation of osteoblasts.

Purification, sequencing and biological activity of polypeptide from velvet antler

The velvet antler polypeptide CNT14 was extracted and purified by gel filtration, ion exchange chromatography and RP C, which showed a single peak in HPLC chromatography and a single band in SDS-PAGE. The molecular weight measured by MALDI/TOF/MS spectrum was 1479. 9028. The polypeptide consisted mostly of Glu, Leu, Val, Pro. The amino acid sequence of the polypeptide was detected with ESI-MS/ MS, and the sequence was E-P-T-V-L-D-E-V-C-L-A-H-G-P. The experiments of biological activity of polypeptide CNT14 in vivo were carried out, and the results show that CNT14 has stimulant effects on the growth of rat HT22 cells. Then we produced the polypeptide CNT14 according the amino acid sequence by solid phase synthesis, confirmed the sequence of the polypeptide to be consistent with the amino acid sequence of polypeptide CNT14 which was separated from the velvet antler.

Synthesis, structure characterization and biological activity of a novel amino acid salt (HAla)(8)(H3O)(10)[PMo12O40](6) center dot 22H(2)O

A novel compound was synthesized and characterized by means of elemental analysis, IR and UV spectra, TG, CV and single crystal X-ray diffraction. The compound crystallized in an orthorhombic space group C222 with a=1. 622 4(3) nm, b=3. 498 4(7) nm, c=1. 301 5(3) nm, V=7. 387 (3) nm(3), Z=6, R-1= 0. 037 3, wR(2)=0. 114 0. The Ala (Ala = alanine) molecules were protonated at the amino nitrogen N (1) and the C (2) of Ala group with the terminal oxygen atom O(15), O(14), O(26) and O(27) of the polyoxometalates participating in the hydrogen bond network. The anti-tumor activity of the title compound was estimated against Hela and Pc-3m cancer cells.

Synthesis, structure and biological activities of 2-(4-methoxybenzoyl)-N-phenyl-2-(1,2,4-triazol-1-yl)thioacetamide

The title compound, 2-(methoxybenzoyl)-N-phenyt-2-(1,2,4-triazol-1-yl)thioacetamide was synthesized by several reactions from 4-methoxyacetophenone, triazole and phenyl isothiocyanate. The structure was identified by elemental analysis, H-1 NMR, MS and IR. The single crystal structure of 2-(methoxybenzoyl)-N-phenyl-2-(1,2,4-triazol-1-yl)thioacetamide was determined with X-ray diffraction. The preliminary bioassays show that the title compound exhibits weak antifungal activities and plant-growth regulatory activity.