Structures of mu O-conotoxins from Conus marmoreus - Inhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons

The muO-conotoxins are an intriguing class of conotoxins targeting various voltage-dependent sodium channels and molluscan calcium channels. In the current study, we have shown MrVIA and MrVIB to be the first known peptidic inhibitors of the transient tetrodotoxin-resistant (TTX-R) Na+ current in rat dorsal root ganglion neurons, in addition to inhibiting tetrodotoxin-sensitive Na+ currents. Human TTX-R sodium channels are a therapeutic target for indications such as pain, highlighting the importance of the muO-conotoxins as potential leads for drug development. Furthermore, we have used NMR spectroscopy to provide the first structural information on this class of conotoxins. MrVIA and MrVIB are hydrophobic peptides that aggregate in aqueous solution but were solubilized in 50% acetonitrile/water. The three-dimensional structure of MrVIB consists of a small beta-sheet and a cystine knot arrangement of the three-disulfide bonds. It contains four backbone loops between successive cysteine residues that are exposed to the solvent to varying degrees. The largest of these, loop 2, is the most disordered part of the molecule, most likely due to flexibility in solution. This disorder is the most striking difference between the structures of MrVIB and the known delta- and omega-conotoxins, which along with the muO-conotoxins are members of the O superfamily. Loop 2 of omega-conotoxins has previously been shown to contain residues critical for binding to voltage-gated calcium channels, and it is interesting to speculate that the flexibility observed in MrVIB may accommodate binding to both sodium and molluscan calcium channels.

Diphenyltin(IV) complexes of the 2-quinolinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazate (Hqaldsme and Hqaldsbz): X-ray crystal structures of Hqaldsme and two conformers of its diphenyltin(IV) complex

New organometallic tin(IV) complexes of the empirical formula Sn(NNS)Ph2Cl (NNS = anionic forms of the 2-quinolinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazate) have been prepared and characterized by IR, electronic, I H NMR and ES mass spectroscopic techniques. The molecular structures of the 2-quinolinecarboxaldehyde Schiff base of S-methyldithiocarbazate (Hqaldsme) and its diphenyltin(IV) complex, Sn(qaldsme)Ph2Cl, have been determined by X-ray diffraction. In the solid state, the ligand remains as the thione tautomer in which the dithiocarbazate chain adopts an E,E configuration and is almost coplanar with the quinoline ring. The Sn(qaldsme)Ph2Cl complex crystallizes in two distinctly different conformationally isomeric forms, each having the same space group but different lattice parameters. X-ray analysis shows that in each polymorph, the tin atom adopts a distorted octahedral geometry with the Schiff base coordinated to it as a uninegatively charged tridentate chelating agent via the quinoline nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. The two phenyl groups occupy axial positions and the chloride ligand occupies the sixth coordination position of the tin atom. The deprotonated ligand adopts an E,E,Z configuration in the complex. (C) 2004 Elsevier Ltd. All rights reserved.

Synthesis, characterization and X-ray crystal structures of dinuclear nickel(II) complexes of a novel potentially hexadentate but functionally tetradentate binucleating ligand

A binucleating potentially hexadentate chelating agent containing oxygen, nitrogen and sulfur as potential donor atoms (H2ONNO) has been synthesized by condensing alpha,alpha-xylenebis(N-methyldithiocarbazate) with 2,4-pentanedione. An X-ray crystallographic structure determination shows that the Schiff base remains in its ketoimine tautomeric form with the protons attached to the imine nitrogen atoms. The reaction of the Schiff base with nickel(II) acetate in a 1:1 stoichiometry leads to the formation of a dinuclear nickel(II) complex [Ni(ONNO)](2) (ONNO2- = dianionic form of the Schiff base) containing N,O-chelated tetradentate ligands, the sulfur donors remaining uncoordinated. A single crystal X-ray structure determination of this dimer reveals that each ligand binds two low spin nickel(II) ions, bridged by a xylyl group. The nickel(II) atoms adopt a distorted square-planar geometry in a trans-N2O2 donor environment. Reaction of the Schiff base with nickel(II) acetate in the presence of excess pyridine leads to the formation of a similar dinuclear complex, [Ni(ONNO)(py)](2), but in this case comprises five coordinate high-spin Ni(II) ions with pyridine ligands occupying the axial coordination sites as revealed by X-ray crystallographic analysis. (c) 2005 Published by Elsevier B.V.

Structural and functional characterization of the conserved salt bridge in mammalian Paneth cell alpha-defensins - Solution structures of mouse cryptdin-4 AND (E15D)-cryptdin-4

Defensins are mediators of mammalian innate immunity, and knowledge of their structure-function relationships is essential for understanding their mechanisms of action. We report here the NMR solution structures of the mouse Paneth cell α-defensin cryptdin-4 (Crp4) and a mutant (E15D)-Crp4 peptide, in which a conserved Glu15 residue was replaced by Asp. Structural analysis of the two peptides confirms the involvement of this Glu in a conserved salt bridge that is removed in the mutant because of the shortened side chain. Despite disruption of this structural feature, the peptide variant retains a well defined native fold because of a rearrangement of side chains, which result in compensating favorable interactions. Furthermore, salt bridge-deficient Crp4 mutants were tested for bactericidal effects and resistance to proteolytic degradation, and all of the variants had similar bactericidal activities and stability to proteolysis. These findings support the conclusion that the function of the conserved salt bridge in Crp4 is not linked to bactericidal activity or proteolytic stability of the mature peptide.

Emerging Structures of Farmer Cooperatives in Vietnam: Case studies from the Mekong Delta

Four farmer groups for mango production and marketing were formed in 2002 in southern Vietnam in response to government support for the creation of market oriented farmer cooperatives. The role and structure of these groups is considered in terms of the degree to which they conform to internationally recognised principles for cooperative formation. Each of the farmer groups studied has evolved in different ways and their degree of compliance with the principles of cooperation varies widely. It is evident that state intervention and market forces may give rise to cooperative structures that differ from that intended under the principles surrounding cooperative law.

Strategic orientations in practice:Exploring the strategic belief structures of line-managers embedded in practice

Recently researchers have started to investigate the cognitive strategic orientations of individual top managers and have pointed out these may be key in determining the direction and success of their organizations in terms of performance, but they have been unable to effectively operationalize this notion in empirical research and this is holding up knowledge development. To make a contribution that helps overcome this limitation a theoretical framework is developed which specifies the different possible cognitive strategic orientations of top managers as well as those of managers at lower organizational levels involved in the strategy process. This theoretical framework is investigated in the empirical phase of the study into strategic orientations in practice. Additional contributions to knowledge of strategic orientation are made in three main domains. Firstly, current knowledge of strategic orientation is largely limited to analysis at the level of the firm whereas there is a lack of understanding of any relationships with practice at lower organizational levels. The exploratory research undertaken for this thesis contributes to new knowledge of different rational, developmental and interactive strategic orientations of front-line managers and this contributes to a cognitive explanation for emergent strategy linked to strategy processes embedded in practice. In theorising the presence of different strategic orientations in practice the discussion highlights the importance of network and spatial embeddedness within enacted environments. Secondly, a contribution to further knowledge of the links between strategy processes and the content of strategies within a retail context is made. The research highlights different strategy processes used in practice by retail front-line managers in a branch network of stores and these are linked to consequences such as different objectives, performance expectations and the fulfilment of personal goals. Thirdly, a contribution to research methodology is made by addressing problems associated with the comparison of cognitive maps.

An investigation into the network structures of eThylene propylene terpolymer elastomers

A series of ethylene propylene terpolymer vulcanizates, prepared by varying termonomer type, cure system, cure time and cure temperature, are characterized by determining the number and type of cross-links present. The termonomers used represent the types currently available in commercial quantities. Characterization is carried out by measuring the C1 constant of the Mooney Rivlin Saunders equation before and after treatment with the chemical probes propane-2-thiol/piperidine and n-hexane thiol/piperidine, thus making it possible to calculate the relative proportions of mono-sulphidic, di-sulphidic and poly- sulphidic cross-links. The cure systems used included both sulphur and peroxide formulations. Specific physical properties are determined for each network and an attempt is made to correlate observed changes in these with variations in network structure. A survey of the economics of each formulation based on a calculated efficiency parameter for each cure system is included. Values of C1 are calculated from compression modulus data after the reliability of the technique when used with ethylene propylene terpolymers had been established. This is carried out by comparing values from both compression and extension stress strain measurements for natural rubber vulcanizates and by assessing the effects of sample dimensions and the degree of swelling. The technique of compression modulus is much more widely applicable than previously thought. The basic structure of an ethylene propylene terpolymer network appears to be independent of the type of cure system used ( sulphur based systems only), the proportions of constituent cross-links being nearly constant.

Characterizing the hierarchical structures of bioactive sol-gel silicate glass and hybrid scaffolds for bone regeneration

Bone is the second most widely transplanted tissue after blood. Synthetic alternatives are needed that can reduce the need for transplants and regenerate bone by acting as active temporary templates for bone growth. Bioactive glasses are one of the most promising bone replacement/regeneration materials because they bond to existing bone, are degradable and stimulate new bone growth by the action of their dissolution products on cells. Sol-gel-derived bioactive glasses can be foamed to produce interconnected macropores suitable for tissue ingrowth, particularly cell migration and vascularization and cell penetration. The scaffolds fulfil many of the criteria of an ideal synthetic bone graft, but are not suitable for all bone defect sites because they are brittle. One strategy for improving toughness of the scaffolds without losing their other beneficial properties is to synthesize inorganic/organic hybrids. These hybrids have polymers introduced into the sol-gel process so that the organic and inorganic components interact at the molecular level, providing control over mechanical properties and degradation rates. However, a full understanding of how each feature or property of the glass and hybrid scaffolds affects cellular response is needed to optimize the materials and ensure long-term success and clinical products. This review focuses on the techniques that have been developed for characterizing the hierarchical structures of sol-gel glasses and hybrids, from atomicscale amorphous networks, through the covalent bonding between components in hybrids and nanoporosity, to quantifying open macroporous networks of the scaffolds. Methods for non-destructive in situ monitoring of degradation and bioactivity mechanisms of the materials are also included. © 2012 The Royal Society.

Properties of seawater bitterns with regard to liquid-desiccant cooling

This study concerns the properties of the concentrated bittern solutions occurring as by-product from solar salt works, in relation to their potential use as liquid desiccants in cooling systems. Solutions of compositions similar to those of bitterns have been made up in the laboratory, as have concentrated mixtures of MgCl2–MgSO4–H2O. Measurements of vapour pressure have been carried out using an isoteniscope and are reported together with measurements of density and viscosity. Several theoretical models representing these properties are reviewed and compared against the experimental results; the average agreement between theory and experiment is within 5% for vapour pressure and better for the preferred models of the other two properties. Based on these findings, an expression is provided for the equilibrium relative humidity of bitterns as a function of concentration relative to raw seawater. The vapour pressures of bittern solutions are found to be similar to those of solutions containing only magnesium chloride but having the same mass fraction of total salts. Therefore magnesium chloride solution is a reasonable model for bitterns for the purpose of developing the proposed cooling system.

Trainer talk:structures of interaction in teacher training classrooms

The subject of this research is interaction and language use in an institutional context, the teacher training classroom. Trainer talk is an interactional accomplishment and the research question is: what structures of talk-in-interaction characterise trainer talk in this institutional setting? While there has been research into other kinds of classroom and into other kinds of institutional talk, this study is the first on trainer discourse. The study takes a Conversation Analysis approach to studying institutional interaction and aims to identify the main structures of sequential organization that characterize teacher trainer talk as well as the tasks and identities that are accomplished in it. The research identifies three main interactional contexts in which trainer talk is done: expository, exploratory and experiential. It describes the main characteristics of each and how they relate to each other. Expository sequences are the predominant interactional contexts for trainer talk. But the research findings show that these contexts are flexible and open to the embedding of the other two contexts. All three contexts contribute to the main institutional goal of teaching teachers how to teach. Trainer identity is related to the different sequential contexts. Three main forms of identity in interaction are evidenced in the interactional contexts: the trainer as trainer, the trainer as teacher and the trainer as colleague. Each of them play an important role in teacher trainer pedagogy. The main features of trainer talk as a form of institutional talk are characterised by the following interactional properties: 1. Professional discourse is both the vehicle and object of instruction - the articulation of reflection on experience. 2. There is a reflexive relationship between pedagogy and interaction. 3. The professional discourse that is produced by trainees is not evaluated by trainers but, rather, reformulated to give it relevant precision in terms of accuracy and appropriacy.

The variance in sales performance explained by the knowledge structures of salespeople

The last major study of sales performance variance explained by salespeople attributes was by Churchill et al. (1985). They examined the effect of role, skills, motivation, personal factors, aptitude, and organizational/environmental factors on sales performance—factors that have dominated the sales performance area. About the same time, Weitz, Sujan, and Sujan (1986) introduced the concepts of salespeople's knowledge structures. Considerable work on the relationship of the elements of knowledge structures and performance can be found in the literature. In this research note, we determine the degree to which sales performance can be explained by knowledge structure variables, a heretofore unexplored area. If knowledge structure variables explain more variance than traditional variables, then this paper would be a call to further research in this area. In examining this research question in a retail context, we find that knowledge structure variables explain 50.2 percent of the variance in sales performance. We also find that variance explained by knowledge structures is significantly different based on gender. The impact of knowledge structures on performance was higher for men than for women. The models using education demonstrated smaller differences.