Solution structure of alpha-conotoxin ImI by H-1 nuclear magnetic resonance

alpha-Conotoxin ImI derives from the venom of Conus imperialis and is the first and only small-peptide ligand that selectively binds to the neuronal alpha(7) homopentameric subtype of the nicotinic acetylcholine receptor (nAChR). This receptor subtype is a possible drug target for several neurological disorders. The cysteines are connected in the pairs Cys2-Cys8 and Cys3-Cys12, To date it is the only alpha-conotoxin with a 4/3 residue spacing between the cysteines, The structure of ImI has been determined by H-1 NMR spectroscopy in aqueous solution, The NMR structure is of high quality, with a backbone pairwise rmsd of 0.34 Angstrom for a family of 19 structures, and comprises primarily a series of nested beta turns. Addition of organic solvent does not perturb the solution structure. The first eight residues of ImI are identical to the larger, but related, conotoxin EpI and adopt a similar structure, despite a truncated second loop. Residues important for binding of ImI to the alpha 7 nAChR are all clustered on one face of the molecule. Once further binding data for EPI and ImI are available, the ImI structure will allow for design of novel alpha(7) nAChR-specific agonists and antagonists with a wide range of potential pharmaceutical applications.

Effect of disorder on quantum phase transitions in anisotropic XY spin chains in a transverse field

We present some exact results for the effect of disorder on the critical properties of an anisotropic XY spin chain in a transverse held. The continuum limit of the corresponding fermion model is taken and in various cases results in a Dirac equation with a random mass. Exact analytic techniques can then be used to evaluate the density of states and the localization length. In the presence of disorder the ferromagnetic-paramagnetic or Ising transition of the model is in the same universality class as the random transverse field Ising model solved by Fisher using a real-space renormalization-group decimation technique (RSRGDT). If there is only randomness in the anisotropy of the magnetic exchange then the anisotropy transition (from a ferromagnet in the x direction to a ferromagnet in the y direction) is also in this universality class. However, if there is randomness in the isotropic part of the exchange or in the transverse held then in a nonzero transverse field the anisotropy transition is destroyed by the disorder. We show that in the Griffiths' phase near the Ising transition that the ground-state energy has an essential singularity. The results obtained for the dynamical critical exponent, typical correlation length, and for the temperature dependence of the specific heat near the Ising transition agree with the results of the RSRODT and numerical work. [S0163-1829(99)07125-8].

Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity

Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its Fe-III complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to Fe-III in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH-H)(2)](+) shows that the trivalent oxidation state is dominant over a wide potential range and that the Fe-II analogue is not a stable form of this complex. The fact that [Fe(NIH-H)(2)](+) cannot-cycle between the Fe-II and Fe-III states suggests that the production of toxic free- radical species, e.g. OH. or O2(.-),is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of Fe-III to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its Fe-III complex are discussed in the context of understanding its anti-tumour activity.

Bird responses at inherent and induced edges in the Murray Mallee, South Australia. 1. Differences in abundance and diversity

We quantified differences in the abundance and diversity of bird species at inherent (naturally occurring) and induced (human-created) edges in the Murray Mallee, South Australia, to explore the effects of anthropogenic landscape modification. Bird species were classified into edge response categories based on numerical differences in abundance between the edge and interior of habitat patches. 'Open-country' species (e.g. Australian Magpie and Little Raven) increased in abundance near induced edges, but were rarely recorded > 200 m into patch interiors or at inherent edges. The Australian Ringneck, Red Wattlebird, Spiny-cheeked Honeyeater, Singing Honeyeater and White-eared Honeyeater increased in abundance near each inherent edge and were classified as 'edge-users'. However, their responses at induced edges varied between sites. The Yellow-plumed Honeyeater, Spotted Pardalote, White-browed Babbler, Chestnut Quail-thrush and Southern Scrub-robin decreased in abundance near one or more induced edges and were classified as 'edge-avoiders' at these sites. The Yellow-plumed Honeyeater, Spotted Pardalote, Chestnut Quail-thrush and Southern Scrub-robin are considered mallee habitat specialists in eastern Australia. These species may be particularly affected by anthropogenic modification of mallee vegetation.

Ameloblast apoptosis and IGF-1 receptor expression in the continuously erupting rat incisor model

Enamel-producing cells (ameloblasts) pass through several phenotypic and functional stages during enamel formation. In the transition between secretory and maturation stages, about one quarter of the ameloblasts suddenly undergo apoptosis. We have studied this phenomenon using the continuously erupting rat incisor model. A special feature of this model is that all stages of ameloblast differentiation are presented within a single longitudinal section of the developing tooth. This permits investigation of the temporal sequence of gene and growth factor receptor expression during ameloblast differentiation and apoptosis. We describe the light and electron microscopic morphology of ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor expression by ameloblasts in the continuously erupting rat incisor model. In the developing rat incisor, ameloblast apoptosis is associated with downregulated expression of the insulin-like growth factor-1 receptor. These data are consistent with the hypothesis that ameloblasts are hard wired for apoptosis and that insulin-like growth factor-1 receptor expression is required to block the default apoptotic pathway. Possible mechanisms of insulin-like growth factor-1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be useful in studies of physiological apoptosis as it presents apoptosis in a predictable pattern in adult tissues.

Expression of galectin-1 in the olfactory nerve pathway of rat

The olfactory neuroepithelium is characterised by the mosaic distribution of primary olfactory neurons that express different odorant receptors and cell surface glycoconjugates. Carbohydrates are believed to form a glycocode that mediates sorting out and fasciculation of primary olfactory axons through interactions with carbohydrate-binding proteins such as galectin-1. In the present study, we describe in detail the expression pattern of galectin-1 in the developing and adult rat olfactory system. We demonstrate that galectin-1 is expressed by olfactory ensheathing cells both in olfactory nerve and within the nerve fibre layer of the olfactory bulb of the embryonic and adult rat. In the adult rat, galectin-1 was preferentially expressed by olfactory ensheathing cells in the nerve fibre layer of the ventromedial and lateral surfaces of the olfactory bulb. Galectin-1 was also expressed by subsets of periglomerular cells and granule cells, particularly in the ventromedial region of the olfactory bulb. In adult rat, the galectin-1 ligand, N-acetyl-lactosamine, was expressed by primary olfactory axons that terminated in glomeruli present in the ventromedial and lateral olfactory bulb. These results suggest that expression of galectin-1 may provide a mechanism for the sorting of subpopulations of axons in the nerve fibre layer of the olfactory bulb during development as well as play a role in the postnatal maintenance of specific glomerular connections. (C) 1999 Elsevier Science B.V. All rights reserved.

Complexes of 1-thia-4,7,10-triazacyclododecane ([12]aneN(3)S) - Synthesis, structure and stability constants

The 12-membered macrocyclic ligand 1-thia-4,7, 10-triazacyclododecane ([12]aneN(3)S) has been synthesised, although upon crystallization from acetonitrile a product in which carbon dioxide had added to one secondary amine in the macrocyclic ring (H[12]aneN(3)SCO(2). H2O) was isolated and subsequently characterised by X-ray crystallography. The protonation constants for [12]aneN(3)S and stability constants with Zn(II), Pb(II), Cd(II) and Cu(II) have been determined either potentiometrically or spectrophotometrically in aqueous solution, and compared with those measured or reported for the ligands 1-oxa-4,7,10-triazacyclododecane ([12]aneN(3)O) and 1,4,7,10-tetraazacyclododecane ([12]aneN(4)). The magnitudes of the stability constants are consistent with trends observed previously for macrocyclic ligands as secondary amine donors are replaced with oxygen and thioether donors although the stability constant for the [Hg([12]aneN(4))](2+) complex has been estimated from an NMR experiment to be at least three orders of magnitude larger than reported previously. Zinc(II), mercury(II), lead(II), copper(II) and nickel(II) complexes of [12]aneN(3)S have been isolated and characterised by X-ray crystallography. In the case of copper(II), two complexes [Cu([12]aneN(3)S)(H2O)](ClO4)(2) and [Cu-2([12]aneN(3)S)(2)(OH)(2)](ClO4)(2) were isolated, depending on the conditions employed. Molecular mechanics calculations have been employed to investigate the relative metal ion size preferences of the [3333], asym-[2424] and sym-[2424] conformation isomers. The calculations predict that the asym-[2424] conformer is most stable for M-N bond lengths in the range 2.00-2.25 Angstrom whilst for the larger metal ions the [3333] conformer is dominant. The disorder seen in the structure of the [Zn([12]aneN(3)S)(NO3)](+) complex is also explained by the calculations. (C) 1999 Elsevier Science Ltd. All rights reserved.

Modeling the optical properties of AlSb, GaSb, and InSb

Optical constants of AlSb, GaSb, and InSb are modeled in the 1-6 eV spectral range. We employ an extension of Adachi's model of the optical constants of semiconductors. The model takes into account transitions at E-0, E-0 + Delta(0), E-1, and E-1 + Delta(1) critical points, as well as higher-lying transitions which are modeled with three damped harmonic oscillators. We do not consider indirect transitions contribution, since it represents a second-order perturbation and its strength should be low. Also, we do not take into account excitonic effects at E-1, E-1 + Delta(1) critical points, since we model the room temperature data. In spite of fewer contributions to the dielectric function compared to previous calculations involving Adachi's model, our calculations show significantly improved agreement with the experimental data. This is due to the two main distinguishing features of calculations presented here: use of adjustable line broadening instead of the conventional Lorentzian one, and employment of a global optimization routine for model parameter determination.

Chemical synthesis, characterization and activity of RK-1, a novel alpha-defensin-related peptide

The 32-residue peptide, RK-1, a novel kidney-derived three disulfide-bonded member of the antimicrobial alpha-defensin family, was synthesized by the continuous now Fmoc-solid phase method. The crude, cleaved and S-reduced Linear peptide was both efficiently folded and oxidized in an acidic solution of aqueous dimethyl sulfoxide. Following purification of the resulting product, it was shown by a variety of analytical techniques, including matrix assisted laser desorption time of flight mass spectrometry, to possess a very high degree of purity. The disulfide bond pairing of the synthetic peptide was determined by H-1-NMR spectroscopy and confirmed to be a Cys(1)-Cys(6), Cys(2)-Cys(4), Cys(3)-Cys(5) arrangement similar to other mammalian alpha-defensin peptides. The synthetic RK-1 was also shown to inhibit the growth of Escherichia coli type strain NCTC 10418, Copyright (C) 2000 European Peptide Society and John Wiley & Sons, Ltd.

1,9-dimethylhypoxanthine from a southern Australian marine sponge Spongosorites species

A Spongosorites sp. collected off southern Australia has yielded 1,9-dimethylhypoxanthine (4). The structure for 4 was solved by spectroscopic analysis.

Substrate-dependent regulation of human arylamine N-acetyltransferase-1 in cultured cells

Arylamine N-acetyltransferase-1 (NAT1) is a polymorphically expressed enzyme that is widely distributed throughout the body. In the present study, we provide evidence for substrate-dependent regulation of this enzyme. Human peripheral blood mononuclear cells cultured in medium supplemented with p-aminobenzoic acid (PABA; 6 mu M) for 24 h showed a significant decrease (50-80%) in NAT1 activity. The loss of activity was concentration-dependent (EC50 similar to 2 mu M) and selective because PABA had no effect on the activity of constitutively expressed lactate dehydrogenase or aspartate aminotransferase. PABA also induced down-regulation of NAT1 activity in several human cell lines grown at confluence. Substrate-dependent downregulation was not restricted to PABA. Addition of other NAT1 substrates, such as p-aminosalicylic acid, ethyl-p-aminobenzoate, or p-aminophenol to peripheral blood mononuclear cells in culture also resulted in significant (P < .05) decreases in NAT1 activity. However, addition of the NAT2-selective substrates sulfamethazine, dapsone, or procainamide did not alter NAT1 activity. Western blot analysis using a NAT1-specific antibody showed that the loss of NAT1 activity was associated with a parallel reduction in the amount of NAT1 protein (r(2) = 0.95). Arylamines that did not decrease NAT1 activity did not alter NAT1 protein levels. Semiquantitative reverse transcriptase polymerase chain reaction of mRNA isolated from treated and untreated cells revealed no effect of PABA on NAT1 mRNA levels. We conclude that NAT1 can be down-regulated by arylamines that are themselves NAT1 substrates. Because NAT1 is involved in the detoxification/activation of various drugs and carcinogens, substrate-dependent regulation may have important consequences with regard to drug toxicity and cancer risk.

Level-one highest weight representations of U-q[g1(1 vertical bar 1)] and associated vertex operators

We study the level-one irreducible highest weight representations of U-q[gl(1\1)] and associated q-vertex operators. We obtain the exchange relations satisfied by these vertex operators. The characters and supercharacters associated with these irreducible representations are calculated'. (C) 2000 Published by Elsevier Science B.V. All rights reserved.

Neuromuscular-skeletal constraints upon the dynamics of unimanual and bimanual coordination

In the first of three experiments, 11 participants generated pronation and supination movements of the forearm, in time with an auditory metronome. The metronome frequency was increased in eight steps (0.25 Hz) from a base frequency of 1.75 Hz. On alternating trials, participants were required to coordinate either maximum pronation or maximum supination with each beat of the metronome. In each block of trials, the axis of rotation was either coincident with the long axis of the forearm, above this axis, or below this axis. The stability of the pronate-on-the-beat pattern, as indexed by the number of pattern changes, and the time of onset of pattern change, was greatest when the axis of rotation of the movement was below the long axis of the forearm. In contrast, the stability of the supinate-on-the-beat pattern was greatest when the axis of rotation of the movement was above the long axis of the forearm. In a second experiment, we examined how changes in the position of the axis of rotation alter the activation patterns of muscles that contribute to pronation and supination of the forearm. Variations in the relative dominance of the pronation and supination phases of the movement cycle across conditions were accounted for primarily by changes in the activation profile of flexor carpi radialis (FCR) and extensor carpi radialis longus (ECR). In the Final experiment we examined how these constraints impact upon the stability of bimanual coordination. Thirty-two participants were assigned at random to one of four conditions, each of which combined an axis of rotation configuration (bottom or top) for each limb. The participants generated both inphase (both limbs pronating simultaneously, and supinating simultaneously) and antiphase (left limb pronating and right limb supinating simultaneously, and vice versa) patterns of coordination. When the position of the axis of rotation was equivalent for the left and the right limb, transitions from antiphase to inphase patterns of coordination were Frequently observed. In marked contrast, when the position of the axis of rotation for the left and right limb was contradistinct, transitions From inphase to antiphase patterns of coordination occurred. The results demonstrated that when movements are performed in an appropriate mechanical context, inphase patterns of coordination are less stable than antiphase patterns.