(FAB01_091) Book reviews

Leon Battista Alberti, 'On the Art of Building in Ten Books' Translated by Joseph Rykwert, Neil Leach and Robert Tavemor L. A. Zhadova (ed.), 'Tatlin' (Budapest 1984). English translation Helen Ross, 'Just For Living, Aboriginal Perceptions of Housing in North West Australia' Tony Fry, 'Design History Australia: A Source Text in Methods and Resources' Phillip Cox and David Moore, 'The Australian Functional Tradition' Lenore Coltheart and Don Fraser (eds.), 'Lamdmarks in Public Works, Engineers and Their Works in New South Wales 1884-1914' Peter Bridges and Don MacDonald, 'James Barnet, Colonial Architect' Don Watson and Judith McKay, 'A Directory of Queensland Architects to 1940' Russell Walden, 'Voices of Silence: New Zealand's Chapel of Futuna' Jeremy Salmond, 'Old New Zealand Houses 1800-1940' Victoria Middleton, 'The Legend of Green Valley' Dyranda Prevost and Ann Rado, 'Living Places' Mark Jackson and Mark Stiles (directors), 'Universal Provider' Lars Lerup, 'Planned Assaults'

Historic Bridge Photographs: The Lahey Collection

Romeo Watkins Lahey (1887-1968) was a distinguished Queensland engineer. He graduated in engineering from the University of Sydney in 1914 and served in World War I from 1915 to 1918 with The Royal Australian Engineers. Following the war, he accepted an offer to remain for a period in England and studied town planning at the University of London. He visited Europe and collected a remarkable set of historic bridge photographs. In the course of this visit, he met Paul Sejourne, a distinguished French bridge engineer, the designer of at Ieast one of the bridges (at Fontpedrouse, pages 25-27) included in this set. When Lahey died, his wife Sybil and daughter Ann took steps to give this remarkable set of 58 historic bridge photographs to The University of Queensland. More recently, Lahey's daughters Ann Neale and Alison Drake have given a set of lantern plates collected by their father, many of which also have photographs of bridges. This volume is divided into three parts: (a) a biography of Romeo Watkins Lahey, written by his daughter, Ann Neale; (b) copies of the original set of 58 bridge photographs, and (c) copies taken from 32 lantern plates. To these have been added captions. Many of the original photographs carried titles; where these are available they have been printed in italics. Further work has been done to identify bridges and where possible the captions include the completion date, major dimensions, locations, and references to published works. Plates 8.1-10 are copies of drawings used as Figures in a book. These drawings have not been copied and the source has not been identified. Two lists of photographs and plates are included - the first in the order of the original collections and a second with bridges listed in the order of material, structural form and date. The collection is of remarkable value to any bridge historian, and is recommended for study by students.

Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease

High-resolution crystal structures are described for seven macrocycles complexed with HIV-1 protease (HIVPR). The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIVPR. Appended to each macrocycle is a transition state isostere and either an acyclic peptide, nonpeptide, or another macrocycle. These cyclic analogues are potent inhibitors of HIVPR, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of HIVPR via the same interactions. Each macrocycle is restrained to adopt a P-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIVPR. A bicyclic inhibitor binds similarly through its secondary amine that lies between its component N-terminal and C-terminal macrocycles. In contrast, the corresponding tertiary amine of the N-terminal macrocycles does not interact with the catalytic aspartates. The amine-aspartate interaction induces a 1.5 Angstrom N-terminal translation of the inhibitors in the active site and is accompanied by weakened interactions with a water molecule that bridges the ligand to the enzyme, as well as static disorder in enzyme flap residues. This flexibility may facilitate peptide cleavage and product dissociation during catalysis. Proteases [Aba(67,95)]HIVPR and [Lys(7),Ile(33),Aba(67,95)]- HIVPR used in this work were shown to have very similar crystal structures.

Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge

We have isolated a family of insect-selective neurotoxins from the venom of the Australian funnel-web spider that appear to be good candidates for biopesticide engineering. These peptides, which we have named the Janus-faced atracotoxins (J-ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they show no homology to any sequences in the protein/DNA databases. The three-dimensional structure of one of these toxins reveals an extremely rare vicinal disulfide bridge that we demonstrate to be critical for insecticidal activity. We propose that J-ACTX comprises an ancestral protein fold that we refer to as the disulfide-directed beta-hairpin.

CysView: protein classification based on cysteine pairing patterns

CysView is a web-based application tool that identifies and classifies proteins according to their disulfide connectivity patterns. It accepts a dataset of annotated protein sequences in various formats and returns a graphical representation of cysteine pairing patterns. CysView displays cysteine patterns for those records in the data with disulfide annotations. It allows the viewing of records grouped by connectivity patterns. CysView's utility as an analysis tool was demonstrated by the rapid and correct classification of scorpion toxin entries from GenPept on the basis of their disulfide pairing patterns. It has proved useful for rapid detection of irrelevant and partial records, or those with incomplete annotations. CysView can be used to support distant homology between proteins. CysView is publicly available at http://research.i2r.a-star.edu.sg/CysView/.

The Mesozoic and Cenozoic motion of Adria (central Mediterranean): a review of constraints and limitations

This paper presents kinematic analysis on the motion of Adria, which is the continental mass that bridges Africa and Europe in the central Mediterranean. Palaeomagnetic data show a general coherence between the motion of Adria and Africa since the Late Paleozoic. This mutual motion, for the period from 120 Ma and the present, is verified by comparing inferred palaeolatitudes from relatively stable parts of Adria (Apulia, Gargano, Istria, and the Southern Alps) and the Hyblean Plateau, with latitudinal changes that are calculated from the motion of Africa with respect to hotspots. Additional constraints on the motion of Adria are provided from the Late Paleozoic-Early Mesozoic passive margin of Adria in the Ionian Sea. The seismic structure of the floor of the Ionian Sea resembles the structure of the oceanic crust in marginal back-arc basins, suggesting that it formed as a small ocean basin. Furthermore, the Ionian lithosphere in the Calabrian arc has been subjected to rapid rollback, which commonly occurs only when the subducting slab is made of oceanic lithosphere. This oceanic domain marks the Pennian-Triassic to Jurassic plate boundary between Adria and Africa, suggesting that a small amount of independent motion between Adria and Africa took place at that time. Since the Jurassic, Adria and Africa have shared a relatively coherent motion path. (C) 2004 Lavoisier SAS. All rights reserved.

An insight into the thermostability of a pair of xylanases: the role of hydrogen bonds

Xylanases are enzymes that are very tolerant to temperature. Their potential use in several biotechnological applications, such as animal food manufacture and pulp bleaching, is due to their intrinsic thermostability. The present report deals with two xylanases, the mesophilic xylanase from Bacillus circulans, BCX, and the thermophilic xylanase from Thermomyces lanuginosus,TLX. These enzymes belong to family 11, and they are the most structurally similar mesophilic-thermophilic pair. Molecular dynamics simulations were employed to investigate the factors responsible for the different thermostabilities exhibited by these structurally similar enzymes. Their active site is their most rigid region, and it is equally rigid at all temperatures. Inter and intramolecular interactions, hydrogen bonds in particular, are the key to the main differences between BCX and TLX. The intramolecular hydrogen bonds and salt bridges are important for maintenance of the backbone rigidity even at high temperature, and the highly solvated surface is a clear optimization in TLX compared with BCX. The main differences between these two enzymes can be found on the fingers domain, which indicates that this domain must be the target for the site-directed mutagenesis responsible for improving the temperature tolerance of this family of enzymes.

A Computational Study of Tetrafluoro-[2.2]Cyclophanes

A computational study of the isomers of tetrafluorinated [2.2]cyclophanes persubstituted in one ring, namely F-4-[2.2]paracyclophane (4), F-4-anti-[2.2]metacyclophane (5a), F-4-syn-[2.2]metacyclophane (5b), and F-4-[2.2]metaparacyclophane (6a and 6b), was carried out. The effects of fluorination on the geometries, relative energies, local and global aromaticity, and strain energies of the bridges and rings were investigated. An analysis of the electron density by B3PW91/6-31+G(d,p), B3LYP/6-31+G(d,p), and MP2/6-31+G(d,p) was carried out using the natural bond orbitals (NBO), natural steric analysis (NSA), and atoms in molecules (AIM) methods. The analysis of frontier molecular orbitals (MOs) was also employed. The results indicated that the molecular structure of [2.2]paracyclophane is the most affected by the fluorination. Isodesmic reactions showed that the fluorinated rings are more strained than the nonfluorinated ones. The NICS, HOMA, and PDI criteria evidenced that the fluorination affects the aromaticity of both the fluorinated and the nonfluorinated rings. The NBO and NSA analyses gave an indication that the fluorination increases not only the number of through-space interactions but also their magnitude. The AIM analysis suggested that the through-space interactions are restricted to the F-4-[2.2]metacyclophanes. In addition, the atomic properties, computed over the atomic basins, shave evidence that not only the substitution, but also the position of the bridges could affect the atomic charges. the first atomic moments, and the atomic volumes.

Determination of mechanical properties of PECVD silicon nitride thin films for tunable MEMS Fabry-Pérot optical filters

This paper reports an investigation on techniques for determining elastic modulus and intrinsic stress gradient in plasma-enhanced chemical vapor deposition (PECVD) silicon nitride thin films. The elastic property of the silicon nitride thin films was determined using the nanoindentation method on silicon nitride/silicon bilayer systems. A simple empirical formula was developed to deconvolute the film elastic modulus. The intrinsic stress gradient in the films was determined by using micrometric cantilever beams, cross-membrane structures and mechanical simulation. The deflections of the silicon nitride thin film cantilever beams and cross-membranes caused by in-thickness stress gradients were measured using optical interference microscopy. Finite-element beam models were built to compute the deflection induced by the stress gradient. Matching the deflection computed under a given gradient with that measured experimentally on fabricated samples allows the stress gradient of the PECVD silicon nitride thin films introduced from the fabrication process to be evaluated.

Structural and Biochemical Correlates of Na(+), K(+)-ATPase Driven Ion Uptake Across the Posterior Gill Epithelium of the True Freshwater Crab, Dilocarcinus pagei (Brachyura, Trichodactylidae)

To better comprehend the structural and biochemical underpinnings of ion uptake across the gills of true freshwater crabs, we performed an ultrastructural, ultracytochemical and morphometric investigation, and kinetically characterized the Na(+), K(+)-ATPase, in posterior gill lamellae of Dilocarcinus pagei. Ultrastructurally, the lamellar epithelia are markedly asymmetrical: the thick, mushroom-shaped, proximal ionocytes contain elongate mitochondria (41% cell volume) associated with numerous (approximate to 14 mu m(2) membrane per mu m(3) cytoplasm), deep invaginations that house the Na(+), K(+)-ATPase, revealed ultracytochemically. Their apical surface is amplified (7.5 mu m(2) mu m(-2)) by stubby evaginations whose bases adjoin mitochondria below the subcuticular space. The apical membrane of the thin, distal ionocytes shows few evaginations (1.6 mu m(2) mu m(-2)), each surrounding a mitochondrion, abundant in the cytoplasm below the subcuticular space; basolateral invaginations and mitochondria are few. Fine basal cytoplasmic bridges project across the hemolymph space, penetrating into the thick ionocytes, suggesting ion movement between the epithelia. Microsomal Na(+), K(+)-ATPase specific activity resembles marine crabs but is approximate to 5-fold less than in species from fluctuating salinities, and freshwater shrimps, suggesting ion loss compensation by strategies other than Na(+) uptake. Enzyme apparent K(+) affinity attains 14-fold that of marine crabs, emphasizing the relevance of elevated K(+) affinity to the conquest of fresh water. Western blotting and biphasic ouabain inhibition disclose two alpha-subunit isoforms comprising distinct functional isoenzymes. While enzyme activity is not synergistically stimulated by NH(4)(+) and K(+), each increases affinity for the other, possibly assuring appropriate intracellular K(+) concentrations. These findings reveal specific structural and biochemical adaptations that may have allowed the establishment of the Brachyura in fresh water. J. Exp. Zool. 313A:508-523, 2010. (C) 2010 Wiley-Liss, Inc.

N-methylation of diamino-substituted macrocyclic complexes: Intramolecular cyclisation

Two new macropolycyclic hexaamines L(2) and L(4) as their copper(II) complexes have been isolated as products from the condensation of the diamino-substituted macrocyclic complex trans-(6,13-dimethyl-1,4,8,11-tetraazacyclo-tetradecane-6,13-diamine)copper(II) [CuL(1)](2+) with aqueous formaldehyde. Both of the complexes exhibit methylene bridges between the pendant amine and the adjacent co-ordinated macrocyclic N-donors. Their crystal structures have been determined: [CuL(2)(NCS)][SCN], triclinic, space group P (1) over bar, a = 7.133(2), b = 9.813(2), c = 16.745(3) Angstrom, alpha = 101.05(2), beta = 99.36(2), gamma = 99.77(2)degrees, Z = 2; [CuL(4)Cl][ClO4]. H2O, triclinic, space group P (1) over bar, a = 9.3327(8), b = 10.8989(6), c = 12.672(1) Angstrom, alpha = 68.591(6), beta = 78.899(6), gamma = 87.384(6)degrees, Z = 2. The complexes exhibit square-pyramidal geometries, and significantly lower-energy electronic maxima relative to their parent complex [CuL(1)](2+). Electrochemistry of [CuL(2)](2+) revealed a reversible Cu-II-Cu-I redox couple, by contrast to those of macromonocyclic analogues.

Super-CHO - A cell line capable of autocrine growth under fully defined protein-free conditions

Chinese Hamster Ovary (CHO) cells are widely used for the large scale production of recombinant biopharmaceuticals. Growth of the CHO-K1 cell line has been demonstrated in serum-free medium containing insulin, transferrin and selenium. In an attempt to get autocrine growth in protein-free medium, DNA coding for insulin and transferrin production was transfected into CHO-K1 cells. Transferrin was expressed well, with clones secreting approximately 1000 ng/10(6)cells/24h. Insulin was poorly expressed, with rates peaking at 5 ng/10(6)cells/24h. Characterisation of the secreted insulin indicated that the CHO cells were incompletely processing the insulin molecule. Site-directed mutagenesis was used to introduce a furin (prohormone converting enzyme) recognition sequence into the insulin molecule, allowing the production of active insulin. However, the levels were still too low to support autocrine growth. Further investigations revealed insulin degrading activity (presumably due to the presence of insulin degrading enzymes) in the cytoplasm of CHO cells. To overcome these problems insulin-like growth factor I (instead of insulin) was transfected into the cells. IGF-1 was completely processed and expressed at rates greater than 500 ng/10(6)cells/24h. In this paper we report autonomous growth of the transfected CHO-K1 cell line expressing transferrin and IGF-1 in protein-free medium without the addition of exogenous growth factors. Growth rates and final cell densities of these cells were identical to that of the parent cell line CHO-K1 growing in insulin, transferrin, and selenium supplemented serum-free media.

Chinese hamster ovary cells produce sufficient recombinant insulin-like growth factor I to support growth in serum-free medium - Serum-free growth of IGF-I producing CHO cells

Insulin-like growth factor I has similar mitogenic effects to insulin, a growth factor required by most cells in culture, and it can replace insulin in serum-free formulations for some cells. Chinese Hamster Ovary cells grow well in serum-free medium with insulin and transferrin as the only exogenous growth factors. An alternative approach to addition of exogenous growth factors to serum-free medium is transfection of host cells with growth factor-encoding genes, permitting autocrine growth. Taking this approach, we constructed an IGF-I heterologous gene driven by the cytomegalovirus promoter, introduced it into Chinese Hamster Ovary cells and examined the growth characteristics of Insulin-like growth factor I-expressing clonal cells in the absence of the exogenous factor. The transfected cells secreted up to 500 ng/10(6) cells/day of mature Insulin-like growth factor I into the conditioned medium and as a result they grew autonomously in serum-free medium containing transferrin as the only added growth factor. This growth-stimulating effect, observed under both small and large scale culture conditions, was maximal since no further improvement was observed in the presence of exogenous insulin.

The uncharged surface features surrounding the active site of Escherichia coli DsbA are conserved and are implicated in peptide binding

DsbA is a protein-folding catalyst from the periplasm of Escherichia coli that interacts with newly translocated polypeptide substrate and catalyzes the formation of disulfide bonds in these secreted proteins. The precise nature of the interaction between DsbA and unfolded substrate is not known. Here, we give a detailed analysis of the DsbA crystal structure, now refined to 1.7 Angstrom, and present a proposal for its interaction with peptide. The crystal structure of DsbA implies flexibility between the thioredoxin and helical domains that may be an important feature for the disulfide transfer reaction. A hinge point for domain motion is identified-the typo IV beta-turn Phe 63-Met 64-Gly 65-Gly 66, which connects the two domains. Three unique features on the active site surface of the DsbA molecule-a groove, hydrophobic pocket, and hydrophobic patch-form an extensive uncharged surface surrounding the active-sits disulfide. Residues that contribute to these surface features are shown to be generally conserved in eight DsbA homologues. Furthermore, the residues immediately surrounding the active-site disulfide are uncharged in all nine DsbA proteins. A model for DsbA-peptide interaction has been derived from the structure of a human thioredoxin:peptide complex. This shows that peptide could interact with DsbA in a manner similar to that with thioredoxin. The active-site disulfide and all three surrounding uncharged surface features of DsbA could, in principle, participate in the binding or stabilization of peptide.

Blood vessels of vocal folds - A videolaryngoscopic study

Objective: To analyze and compare the incidence and visual characteristics of blood vessels on the superior surface of vocal folds with polyps, nodules, and minimal structural alterations (ie, sulci, cysts, and mucosal bridges). Design: Cross-sectional study. Setting: Academic research. Patients: A total of 280 videolaryngoscopic images were randomly selected and classified into the following 4 groups of 70 patients each: the vocal nodule (VN) group, the polyp group, the minimal structural alterations (MSA) group, and the control group. Main Outcome Measures: Laryngoscopic images were assessed for visible blood vessels and for the orientation and characteristics of the vessels. Isolated ectasias with clear boundaries were excluded. Results: The highest incidence of visible vessels was observed in the MSA group (91.4%), followed by the polyp (77.1%), VN (44.7%), and control (31.4%) groups. Longitudinal and transverse vessels were found more frequently in the MSA (74.3% and 37.1%) and polyp (65.7% and 22.9%) groups than in the VN (34.3% and 12.9%) and control (25.7% and 5.7%) groups. Tangled vessels were found only in the MSA group (8.6%). Abrupt changes in the caliber of the vessels and sinuous vessels were ob served only in the polyp (21.4% and 5.7%) and MSA (61.4% and 27.1%) groups. Conclusions: The main differences in the incidence and characteristics of visible blood vessels occurred between 2 pairs of groups: MSA-polyp and VN-control. The incidence was significantly higher in the MSA group than in the polyp group, and the incidence in both the MSA group and the polyp group was also significantly higher than that in the VN and control groups. The greatest variations were found in the MSA group, including the presence of tangled blood vessels (which was observed only in this group).