A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).     

A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia

The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.     

Water-Quality Monitoring in Anguilla

Anguilla is a UK overseas (non-independent) territory in the Caribbean. It is a small middle-income island with a population of 13 000, and recent statistics indicate that it is more dependent on tourism than any other country or territory in the world. Rapid population growth and development have placed more emphasis on the need for human health and environmental protection. For the first time, a systematic water-quality monitoring programme has been developed, based on the realities of the local situation, e.g. low resource base, limited capabilities, dependence on household rainwater catchment, storage cisterns, and a poor water-supply network. Development of the programme incorporated the key themes of pragmatic, realistic, incremental, responsive, and consultative approaches.     

Analysis of a stiffener intersection eccentricity in a steel containment

Containment structures have several regions in which the continuity of the cylindrical pressure boundary is interrupted, e.g., shell penetrations, discontinuous stiffeners, and changes in the shell thickness. Significant strain concentrations can occur in these areas of discontinuity. The Sandia National Laboratories 1:8-scale steel containment equipment hatch was analyzed as an example of an eccentricity at a stiffener intersection.A portion of the as-built 1:8-scale model was modeled with the ANSYS general purpose finite element program using triangular, thin shell finite elements. The overall size of the model was determined from Saint-Venant type considerations of the stress field around the hatch. Shell elements were used to model the ring and formed stiffeners. Geometric and material nonlinear behavior were included. The model was loaded using discrete load steps up to a pressure of 165 psig. At this pressure, the maximum strain was 19.7 percent in the formed stiffener near its intersection with the ring stiffener. The finite element solution demonstrated the very localized nature of the strain field near the ring/formed stiffener intersection.In an attempt to reduce analysis costs, a small portion of the 1:8-scale model immediately surrounding the ring/formed stiffener intersection was selected for further analysis. Two smaller models, a ring/formed stiffener intersection and a ring/circular stiffener intersection, were studied. The models were significantly smaller than the regions used previously. A comparison of the two intersection models showed that the circular stiffener is a more efficient configuration.     

Structural characterisation of apatite coatings

The current, most frequently employed, commercial route to produce hydroxyapatite prosthetic coatings is plasma spraying. However, this has several important limitations especially for textured surfaces. Low temperature methods of coating fabrication such as cathodic electrodeposition are attractive alternatives. However, quantitative characterisation of the phase composition of thin electrodeposited coatings can be problematic. An X-ray diffraction method, which provides quantitative compositional information without reference to external or internal standards, is introduced and validated. The method can also be applied when Bragg peaks from the supporting substrate are apparent within the data and preferred orientation can be tolerated. This method has been used to examine in detail the microstructure of electrodeposited coatings which are compared directly with those formed by a commercial plasma spraying process.We show that, unlike the plasma sprayed coatings, the electrodeposited material consists of a single crystalline phase (hydroxyapatite) and a significantly reduced amorphous phase. The electrodeposited coatings also possess significantly more microstrain and a smaller crystallite size than the corresponding plasma sprayed material.     

Characteristics of Milk Powders Produced by Spray Freeze Drying

Skim and whole milk powders were manufactured at lab scale by spray freeze drying (SFD), using liquid nitrogen as the cryogen. The polydispersity of droplet/particle sizes was limited using an encapsulator nozzle to atomize the feed. Particle morphology was examined using a scanning electron microscope. Samples were compared with equivalent spray-dried powders in tests of wettability and dissolution in water. The spray freeze-dried powders were found to be highly porous, with a uniform structure of pores throughout the entire particles. When tested in water, SFD skim milk powders wetted roughly three times as fast as industrially spray-dried agglomerated skim milk powders and were observed to dissolve rapidly by breaking down into smaller particles.