Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from substituted benzene substrates

Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Arene hydrates have also been synthesised, in enantiopure form, from the corresponding dihydroarene oxide or trans-bromoacetate precursors. Biotransformation of one arene hydrate enantiomer resulted in a toluene-dioxygenase catalysed cis-dihydroxylation to yield a benzene cis-triol metabolite.

Purification of a cathepsin L-like proteinase secreted by adult Fasciola hepatica

A cysteine proteinase released in vitro by Fasciola hepatica was purified to homogeneity by Sephacryl S-200 gel filtration chromatography followed by QAE-Sephadex chromatography. The purified enzyme resolves as a single band with an apparent molecular size of 27 kDa on reducing SDS-polyacrylamide gel electrophoresis; however, under non-reducing conditions it migrates as multiple bands, each with enzymatic activity, in the apparent molecular size range 60-90 kDa. The sequence of the first 20 N-terminal amino acids of the enzyme shows considerable homology with cathepsin L-like proteinases. Immunolocalisation studies revealed that the cathepsin L-like proteinase is concentrated within vesicles in the gut epithelial cells of liver fluke.

A cleavable network based on crosslinked star polymers containing acid-labile diacetal crosslinks: Synthesis, characterization and hydrolysis

A hydrolyzable model network comprising interconnected star polymers was prepared by the sequential group transfer polymerization of methyl methacrylate and the acid-labile diacetal-based dimethacrylate crosslinker bis[(2-methacryloyloxy)ethoxymethyl] ether. in contrast to other polymer networks previously synthesized by our group, all the branching points of this polymer network were found to hydrolyze under mildly acidic conditions, giving a linear copolymer with the theoretically expected molecular weight and composition. The ease of hydrolysis of this polymer network renders it a good candidate for use in the biomedical field. The characterization of the synthesized network, its linear and star polymer precursors and the hydrolysis products of the network and its precursors, by a variety of techniques, established the successful synthesis and hydrolysis of this well-defined polymer nanostructure.

Synthesis and characterization of amphiphilic star copolymers of 2-(dimethylamino) ethyl methacrylate and methyl methacrylate: Effects of architecture and composition

Six amphiphilic star copolymers comprising hydrophilic units of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and hydrophobic units of methyl methacrylate (MMA) were prepared by the sequential group transfer polymerization (GTP) of the two comonomers and ethylene glycol dimethacrylate (EGDMA) cross-linker. Four star-block copolymers of different compositions, one miktoarm star, and one statistical copolymer star were synthesized. The molecular weights (MWs) and MW distributions of all the star copolymers and their linear homopolymer and copolymer precursors were characterized by gel permeation chromatography (GPC), while the compositions of the stars were determined by proton nuclear magnetic resonance (H-1 NMR) spectroscopy. Tetrahydrofuran (THF) solutions of all the star copolymers were characterized by static light scattering to determine the absolute weight-average MW ((M) over bar (w)) and the number of arms of the stars. The R, of the stars ranged between 359,000 and 565,000 g mol(-1), while their number of arms ranged between 39 and 120. The star copolymers were soluble in acidic water at pH 4 giving transparent or slightly opaque solutions, with the exception of the very hydrophobic DMAEMA(10)-b-MMA(30)-star, which gave a very opaque solution. Only the random copolymer star was completely dispersed in neutral water, giving a very opaque solution. The effective pKs of the copolymer stars were determined by hydrogen ion titration and were found to be in the range 6.5-7.6. The pHs of precipitation of the star copolymer solutions/dispersions were found to be between 8.8-10.1, except for the most hydrophobic DMA-EMA(10)-b-MMA(30)-Star, which gave a very opaque solution over the whole pH range. (c) 2006 Elsevier Ltd. All rights reserved.

Synthesis and characterization of star polymers and cross-linked star polymer model networks with cores based on an asymmetric, hydrolyzable dimethacrylate cross-linker

A hydrolyzable dimethacrylate cross-linker, 2-methyl-2,4-pentanediol dimethacrylate (MPDMA), was synhesized by the reaction of 2-methyl-2,4-pentanediol and methacryloyl chloride in the presence of triethylamine. This cross-linker was used to prepare a neat cross-linker network and three cross-linked star polymer model networks (CSPMNs) of methyl methacrylate (MMA), as well as star-shaped polymers of MMA, by group transfer polymerization (GTP). Gel permeation chromatography (GPC) in tetrahydrofuran (THF) confirmed the narrow molecular weight distributions (MWDs) of the linear polymer precursors, and demonstrated the increase in molecular weight (MW) on each successive addition of cross-linker or monomer. Characterization of the star polymers by static light scattering (SLS) in THF showed that star polymers with MPDMA cores bear a relatively small number of arms, between 7 and 35. All star polymers and polymer networks containing the MPDMA cross-linker were hydrolyzed at room temperature in neat trifluoroacetic acid to yield lower-MW products.

Synthesis and characterization of polymer networks and star polymers containing a novel, hydrolyzable acetal-based dimethacrylate cross-linker

An acid-labile dimethaerylate acetal cross-linker,di(methacryloyloxy-l-ethoxy)methane(DMOEM), was synthesized by the reaction of 2-hydroxyethyl methacrylate and paraformaldehyde using p-toluenesulfonic acid and toluene as catalyst and solvent, respectively. Group transfer polymerization was employed to use this cross-linker in the preparation of nine hydrolyzable polymer structures: one neat cross-linker network, one randomly cross-linked network of methyl methacrylate (MMA), and seven star-shaped polymers of MMA. Gel permeation chromatography (GPC) in tetrahydrofuran (THF) confirmed the narrow molecular weight distributions of the linear polymer precursors to the stars and demonstrated the increase in molecular weight upon the addition of cross-linker for the formation of star-shaped polymers. Characterization of the star polymers in THF using static light scattering and GPC showed that the molecular weights and the number of arms of each star polymer increased with an increase in the molar ratio of cross-linker to initiator and with a decrease in the molar ratio of monomer to initiator. The star polymers with DMOEM cores bore a smaller number of arms than those cross-linked with the non-hydrolyzable commercial cross-linker ethylene glycol dimethacrylate due to the bulkier structure of DMOEM. All DMOEM-containing polymer networks and star polymers were completely hydrolyzed within 48 h using hydrochloric acid in THF.

Synthesis and characterization of star polymers and cross-linked star polymer model networks containing a novel, silicon-based, hydrolyzable cross-linker

An acid-labile dimethacrylate cross-linker, dimethyldi(methacryloyloxy-l-ethoxy)silane (DMDMAES), was synthesized by the reaction of 2-hydroxyethyl methacrylate (HEMA) and dichlorodimethylsilane in the presence of triethylamine. Group transfer polymerization (GTP) was employed to use this cross-linker in the preparation of six hydrolyzable polymer structures: one neat cross-linker network, one randomly cross-linked network of methyl methacrylate (MMA), two star-shaped polymers of MMA, and two cross-linked star polymer model networks (CSPMNs) of MMA. A nonhydrolyzable CSPMN of MMA, based on a stable cross-linker, was also synthesized. Gel permeation chromatography (GPC) in tetrahydrofuran (THF) confirmed the narrow molecular weight distributions (MWDs) of the linear polymer precursors and demonstrated the increase in molecular weight (MW) upon each successive addition of cross-linker or monomer. Characterization by static light scattering (SLS) and GPC showed that star polymers with DMDMAES cores bear a relatively small number of arms, around 7. All star polymers and polymer networks were hydrolyzed using hydrochloric acid in THF. While the MWs of the products from the hydrolysis of the star polymers, the neat cross-linker network, and the randomly cross-linked network were as expected, those from the CSPMNs were of a much higher than expected MW, indicating extensive star-star coupling.

The ventral habenulae of zebrafish develop in prosomere 2 dependent on Tcf7l2 function

The conserved habenular neural circuit relays cognitive information from the forebrain into the ventral mid- and hindbrain. In zebrafish, the bilaterally formed habenulae in the dorsal diencephalon are made up of the asymmetric dorsal and symmetric ventral habenular nuclei, which are homologous to the medial and lateral nuclei respectively, in mammals. These structures have been implicated in various behaviors related to the serotonergic/dopaminergic neurotransmitter system. The dorsal habenulae develop adjacent to the medially positioned pineal complex. Their precursors differentiate into two main neuronal subpopulations which differ in size across brain hemispheres as signals from left-sided parapineal cells influence their differentiation program. Unlike the dorsal habenulae and despite their importance, the ventral habenulae have been poorly studied. It is not known which genetic programs underlie their development and why they are formed symmetrically, unlike the dorsal habenulae. A main reason for this lack of knowledge is that the vHb origin has remained elusive to date.

Ionothermal, microwave-assisted synthesis of indium(III) selenide

Microcrystalline indium(III) selenide was prepared from a diphenyl diselenide precursor and a range of chloroindate(III) ionic liquids via a microwave-assisted ionothermal route; this is the first report on the use of either microwave irradiation or ionic liquids to prepare this material. The influence of the reaction temperature, dilution with a spectator ionic liquid and variation of the cation and the anion of the ionic liquid on the product morphology and composition were investigated. This resulted in a time-efficient and facile one-pot reaction to produce microcrystalline indium(III) selenide. The product formation in the ionic liquids has been monitored using Raman spectroscopy. The products have been characterised using PXRD, SEM and EDX. Advantages of this new route, such as the ease of solubilisation of all reactants into one phase at high concentration, the negligible vapour pressure irrespective of the reaction temperature, very fast reaction times, ease of potential scale-up and reproducibility are discussed.

A Burkholderia cenocepacia MurJ (MviN) homolog is essential for cell wall peptidoglycan synthesis and bacterial viability

The cell wall peptidoglycan (PG) of Burkholderia cenocepacia, an opportunistic pathogen, has not yet been characterized. However, the B. cenocepacia genome contains homologs of genes encoding PG biosynthetic functions in other bacteria. PG biosynthesis involves the formation of the undecaprenyl-pyrophosphate-linked N-acetyl glucosamine-N-acetyl muramic acid-pentapeptide, known as lipid II, which is built on the cytosolic face of the cell membrane. Lipid II is then translocated across the membrane and its glycopeptide moiety becomes incorporated into the growing cell wall mesh; this translocation step is critical to PG synthesis. We have investigated candidate flippase homologs of the MurJ family in B. cenocepacia. Our results show that BCAL2764, herein referred to as murJBc, is indispensable for viability. Viable B. cenocepacia could only be obtained through a conditional mutagenesis strategy by placing murJBc under the control of a rhamnose-inducible promoter. Under rhamnose depletion, the conditional strain stopped growing and individual cells displayed morphological abnormalities consistent with a defect in PG synthesis. Bacterial cells unable to express MurJBc underwent cell lysis, while partial MurJBc depletion sensitized the mutant to the action of β-lactam antibiotics. Depletion of MurJBc caused accumulation of PG precursors consistent with the notion that this protein plays a role in lipid II flipping to the periplasmic compartment. Reciprocal complementation experiments of conditional murJ mutants in B. cenocepacia and Escherichia coli with plasmids expressing MurJ from each strain indicated that MurJBc and MurJEc are functional homologs. Together, our results are consistent with the notion that MurJBc is a PG lipid II flippase in B. cenocepacia.

Law and Society: Volume I: Historical development

The thriving and well-established field of Law and Society (also referred to as Sociolegal Studies) has diverse methodological influences; it draws on social-scientific and arts-based methods. The approach of scholars researching and teaching in the field often crosses disciplinary borders, but, broadly speaking, Law and Society scholarship goes behind formalism to investigate how and why law operates, or does not operate as intended, in society. By exploring law’s connections with broader social and political forces—both domestic and international—scholars gain valuable perspectives on ideology, culture, identity, and social life. Law and Society scholarship considers both the law in contexts, as well as contexts in law.
Law and Society flourishes today, perhaps as never before. Academic thinkers toil both on the mundane and the local, as well as the global, making major advances in the ways in which we think both about law and society. Especially over the last four decades, scholarly output has rapidly burgeoned, and this new title from Routledge’s acclaimed Critical Concepts in Law series answers the need for an authoritative reference collection to help users make sense of the daunting quantity of serious research and thinking.
Edited by the leading scholars in the field, Law and Society brings together in four volumes the vital classic and contemporary contributions. Volume I is dedicated to historical antecedents and precursors. The second volume covers methodologies and crucial themes. The third volume assembles key works on legal processes and professional groups, while the final volume of the collection focuses on substantive areas. Together, the volumes provide a one-stop ‘mini library’ enabling all interested researchers, teachers, and students to explore the origins of this thriving subdiscipline, and to gain a thorough understanding of where it is today.

Law and Society: Volume II: Methodologies and themes

The thriving and well-established field of Law and Society (also referred to as Sociolegal Studies) has diverse methodological influences; it draws on social-scientific and arts-based methods. The approach of scholars researching and teaching in the field often crosses disciplinary borders, but, broadly speaking, Law and Society scholarship goes behind formalism to investigate how and why law operates, or does not operate as intended, in society. By exploring law’s connections with broader social and political forces—both domestic and international—scholars gain valuable perspectives on ideology, culture, identity, and social life. Law and Society scholarship considers both the law in contexts, as well as contexts in law.
Law and Society flourishes today, perhaps as never before. Academic thinkers toil both on the mundane and the local, as well as the global, making major advances in the ways in which we think both about law and society. Especially over the last four decades, scholarly output has rapidly burgeoned, and this new title from Routledge’s acclaimed Critical Concepts in Law series answers the need for an authoritative reference collection to help users make sense of the daunting quantity of serious research and thinking.
Edited by the leading scholars in the field, Law and Society brings together in four volumes the vital classic and contemporary contributions. Volume I is dedicated to historical antecedents and precursors. The second volume covers methodologies and crucial themes. The third volume assembles key works on legal processes and professional groups, while the final volume of the collection focuses on substantive areas. Together, the volumes provide a one-stop ‘mini library’ enabling all interested researchers, teachers, and students to explore the origins of this thriving sub discipline, and to gain a thorough understanding of where it is today.

Law and Society: Volume III: Legal Processes and Professional Groups within the Legal Field

The thriving and well-established field of Law and Society (also referred to as Socio-legal Studies) has diverse methodological influences; it draws on social-scientific and arts-based methods. The approach of scholars researching and teaching in the field often crosses disciplinary borders, but, broadly speaking, Law and Society scholarship goes behind formalism to investigate how and why law operates, or does not operate as intended, in society. By exploring law’s connections with broader social and political forces—both domestic and international—scholars gain valuable perspectives on ideology, culture, identity, and social life. Law and Society scholarship considers both the law in contexts, as well as contexts in law.
Law and Society flourishes today, perhaps as never before. Academic thinkers toil both on the mundane and the local, as well as the global, making major advances in the ways in which we think both about law and society. Especially over the last four decades, scholarly output has rapidly burgeoned, and this new title from Routledge’s acclaimed Critical Concepts in Law series answers the need for an authoritative reference collection to help users make sense of the daunting quantity of serious research and thinking.
Edited by the leading scholars in the field, Law and Society brings together in four volumes the vital classic and contemporary contributions. Volume I is dedicated to historical antecedents and precursors. The second volume covers methodologies and crucial themes. The third volume assembles key works on legal processes and professional groups, while the final volume of the collection focuses on substantive areas. Together, the volumes provide a one-stop ‘mini library’ enabling all interested researchers, teachers, and students to explore the origins of this thriving sub discipline, and to gain a thorough understanding of where it is today.

Law and Society: Volume IV: Substantive Areas

The thriving and well-established field of Law and Society (also referred to as Sociolegal Studies) has diverse methodological influences; it draws on social-scientific and arts-based methods. The approach of scholars researching and teaching in the field often crosses disciplinary borders, but, broadly speaking, Law and Society scholarship goes behind formalism to investigate how and why law operates, or does not operate as intended, in society. By exploring law’s connections with broader social and political forces—both domestic and international—scholars gain valuable perspectives on ideology, culture, identity, and social life. Law and Society scholarship considers both the law in contexts, as well as contexts in law.
Law and Society flourishes today, perhaps as never before. Academic thinkers toil both on the mundane and the local, as well as the global, making major advances in the ways in which we think both about law and society. Especially over the last four decades, scholarly output has rapidly burgeoned, and this new title from Routledge’s acclaimed Critical Concepts in Law series answers the need for an authoritative reference collection to help users make sense of the daunting quantity of serious research and thinking.
Edited by the leading scholars in the field, Law and Society brings together in four volumes the vital classic and contemporary contributions. Volume I is dedicated to historical antecedents and precursors. The second volume covers methodologies and crucial themes. The third volume assembles key works on legal processes and professional groups, while the final volume of the collection focuses on substantive areas. Together, the volumes provide a one-stop ‘mini library’ enabling all interested researchers, teachers, and students to explore the origins of this thriving sub discipline, and to gain a thorough understanding of where it is today.

Feleucin-BO1: A Novel Antimicrobial Non-Apeptide Amide from the Skin Secretion of the Toad, Bombina orientalis, and Design of a Potent Broad-Spectrum Synthetic Analogue, Feleucin-K3

Feleucins-BV1 and -BV2 are recently-described prototypes of a novel antimicrobial nonapeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μM) but was inactive (> 250 μM) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly-enhanced potency and spectrum of activity. The MICs of F-K3 against the reference microorganisms were 7 μM (S. aureus), 14 μM (E. coli) and 7 μM (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.