bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyse du partage d'informations contextuelles dans deux formes d'interaction sportives : coopérative et concurrentielle
Authors: Poizat Germain , Sève Carole , Serres Guillaume , Saury Jacques
Published: February 2009

RESUME Plusieurs études ont souligné l’importance du partage d’informations contextuelles lors de tâches coopératives. S’inspirant de la notion de contexte partagé, notre étude visait à préciser le partage d’informations contextuelles dans deux formes d’interaction en tennis de table : une coopérative et une concurrentielle. Afin de reconstruire le partage d’informations contextuelles du point de vue des acteurs, cette étude a été menée en référence au cadre théorique et méthodologique du cours d’action (Theureau, 1992). Elle a permis : a)  d’identifier trois formes typiques de partage des informations contextuelles ; et b)  de préciser les processus régulant le partage de ces informations et les processus de vérification de ce partage. La discussion s’organise autour de : a)  l’indétermination, la complexité et la coconstruction de l’intelligibilité mutuelle dans les deux formes d’interaction sportives ; et b)  la relation de codéfinition existante, en tennis de table, entre l’efficacité relative des deux joueurs et le partage d’informations contextuelles.
Putting Reusability First: A Paradigm Switch in Remote Laboratories Engineering
Authors: Gravier Christophe , Fayolle Jacques , Lardon Jérémy , Bayard Bernard , Dusser Gaétan , Vérot Romain
Published: February 2009

In this paper, we present a new devices brought online thanks to our Collaborative Remote Laboratories framework. Whereas previous devices integrated in our remote laboratory belongs to the domain of electronics, such as Vector Network Analyzers, the devices at the concern in this paper are, on one hand, an antenna workbench, and on the other, an homemade switching device, which embeds several electronic components. Because the middleware and framework for our environment were designed to be reusable, we wanted to put it to the test by integrating new and different devices in our Online Engineering catalog. After presenting the devices to be put online, we will expose the software development efforts required in regards to the reusability of the solution. As a consequence, the expose work and results tend to make the Online Engineering software architects to think reusability first, breaking with the current trends to implement Remote Labs one after the other, without much reusability, apart the capitalized experience. In this, we defend a paradigm switch in our current engineering approaches for Remote Laboratories implementations: Reusability should be thought first.
Believing in the purpose of events—why does it occur, and is it supernatural?
Authors: Svedholm Annika M. , Lindeman Marjaana , Lipsanen Jari
Published: February 2009

What is the cognitive basis for the common belief that random events have a purpose, and are these beliefs a form of supernatural thinking, as Bering has suggested? Two questionnaire studies with Finnish volunteer participants (N = 2650, 1830 females, mean age 26) used structural equation modelling (SEM) to test the hypotheses that beliefs in the purpose of events are part of the same phenomenon as paranormal beliefs and that confusions of core knowledge of the psychological, biological and physical domains predict both sets of beliefs. In Study 1, participants were not given a definition of purpose, and in Study 2, purpose was explicitly defined as entailing planning by a supernatural agent. The results from both studies supported the predictions. The results indicate that construing events in terms of purpose is not a universal tendency but an individual cognitive bias that can be accounted for by false analogies from intuitive psychology, biology and physics. Copyright © 2009 John Wiley & Sons, Ltd.
A Reduced SNARE Model for Membrane Fusion
Authors: Robson Marsden Hana , Elbers Nina A. , Bomans Paul H. H. , Sommerdijk Nico A. J. M. , Kros Alexander
Published: February 2009

Ein Minimalmodell für die SNARE‐vermittelte Fusion biologischer Membranen wurde entwickelt. Die Fusion zwischen zwei Populationen von Liposomen wird durch ein Paar komplementärer lipidierter Oligopeptide gelenkt, die nichtkovalente doppelt gewendelte Komplexe bilden und dadurch die Membranen in unmittelbare Nähe zueinander zwingen. Das Modellsystem gibt die Schlüsselmerkmale in vivo stattfindender Fusionsereignisse wieder.

magnified image
Helical‐Ribbon Formation by a β‐Amino Acid Modified Amyloid β‐Peptide Fragment
Authors: Castelletto Valeria , Hamley Ian W. , Hule Rohan A. , Pochan Darrin
Published: February 2009

Familienzuwachs: Die Einführung von β‐Aminosäureresten in ein modifiziertes Amyloid‐β‐peptidfragment ergibt definierte helicale Nanobänder (siehe Kryo‐TEM‐Aufnahme), die β‐Stränge mit hauptsächlich senkrechter Orientierung zur Bandachse enthalten. Die Bänder ordnen sich bei höherer Konzentration in einer nematischen Phase an, die sich bei Anlegen von Scherkräften ausrichtet. Diese Bandstruktur ist ein neues Mitglied der bekannten Familie von β‐Peptid‐Sekundärstrukturen.

magnified image
Dynamische Kristalle: visuell wahrnehmbare mechanochemische Lumineszenzänderungen von Gold‐ und anderen Übergangsmetallkomplexen
Authors: Balch Alan L.
Published: February 2009

Ungewöhnliche Lumineszenzänderung: Bei bestimmten Kristallkomplexen von Gold, Platin und Vanadium bewirkt ein Zermahlen der Kristalle deutliche Veränderungen der Lumineszenz oder Farbe. Im Bild ist die Umwandlung von farblosem [(F5C6Au)2(μ‐1,4‐CN2C6H4)]‐Kristallpulver von einer blau emittierenden Form (λmax=415 nm) in eine gelb/grün emittierende Form (λmax=533 nm) beim Zermahlen zu sehen. Der Prozess ist reversibel.

magnified image
Universal Scaffold for Fluorescent Conjugated Organoborane Polymers
Authors: Li Haiyan , Jäkle Frieder
Published: February 2009

Aufgemotzte Polymere: Ein vielseitiges und stark emittierendes konjugiertes Polymergerüst wird erhalten, wenn Nucleophile labile Bromatome am Rückgrat eines Fluorenylboran‐Polymers ersetzen (siehe Bild). Durch solche einfachen Modifizierungen lassen sich die Stabilität sowie das thermische und photophysikalische Verhalten einstellen, sodass lumineszierende Polymere mit Anionenbindungsvermögen zugänglich werden.

magnified image
Photoprogrammable Organic Light‐Emitting Diodes
Authors: Zacharias Philipp , Gather Malte C. , Köhnen Anne , Rehmann Nina , Meerholz Klaus
Published: February 2009

Licht im Speicher: Der Einbau eines vernetzbaren photochromen Dithienylperfluorcyclopentens (DTE) in organische Leuchtdioden (OLEDs) ermöglicht die Individualisierung der Emissionsfläche, z. B. für die Anwendung in Anzeigeelementen. Das Arbeitsprinzip beruht auf dem Schalten der Injektionsbarriere für Löcher (positive Ladungsträger). Sehr große AN/AUS‐Verhältnisse von bis zu 3000 für die Stromstärke und die Elektrolumineszenz wurden erreicht.

magnified image
Icosahedral DNA Nanocapsules by Modular Assembly
Authors: Bhatia Dhiraj , Mehtab Shabana , Krishnan Ramya , Indi Shantinath S. , Basu Atanu , Krishnan Yamuna
Published: February 2009

In der Falle: Durch molekulare Selbstorganisation erzeugte DNA‐Polyeder könnten als Nanokäfige für den gerichteten Transport von verkapselten Spezies dienen. Das Funktionsprinzip wurde für den komplexesten aller DNA‐basierten platonischen Festkörper gezeigt: Während der stufenweisen Amalgamierung diskreter Polyeder zu Ikosaedern wurden Gold‐Nanopartikel (GNPs) aus der Lösung eingekapselt (siehe Illustration und TEM‐Bild ikosaederischer Käfige mit verkapselten GNPs).

magnified image
Highly Enantioselective Pictet–Spengler Reactions with α‐Ketoamide‐Derived Ketimines: Access to an Unusual Class of Quaternary α‐Amino Amides
Authors: Bou‐Hamdan Farhan R. , Leighton James L.
Published: February 2009

N‐Arylamide wurden als effiziente steuernde und aktivierende Gruppen für Lewis‐saure Chlorosilane im ersten einfachen und allgemeinen Verfahren für die hoch enantioselektive Pictet‐Spengler‐Reaktion mit Ketiminen aus α‐Ketoamiden eingesetzt. Als Produkte werden quartäre α‐Aminosäure‐Derivate erhalten (siehe Schema).

magnified image
Challenging the Metallocene Dominance in Actinide Chemistry with a Soft PNP Pincer Ligand: New Uranium Structures and Reactivity Patterns
Authors: Cantat Thibault , Graves Christopher R. , Scott Brian L. , Kiplinger Jaqueline L.
Published: February 2009

U wie ungewohnt: Der Austausch von C5Me5 gegen einen „weichen“ PNP‐ Pinzettenliganden mit besonderen elektronischen und sterischen Eigenschaften erzeugte neue Reaktivitäts‐ und Strukturmuster in der Actinoidenreihe (siehe Bild, py–O=Pyridin‐N‐oxid). Die neuen Liganden unterstützen nicht nur niedervalente Uranverbindungen, sondern auch hochvalente Uran(VI)‐Spezies.

magnified image
Parallel Kinetic Resolution Approach to the Cyathane and Cyanthiwigin Diterpenes Using a Cyclopropanation/Cope Rearrangement
Authors: Miller Laura C. , Ndungu J. Maina , Sarpong Richmond
Published: February 2009

Parallel gearbeitet: Die stereodivergente parallele kinetische Racematspaltung eines Diengemischs mithilfe der Davies‐Katalysatoren [Rh2{(S)‐dosp}4] oder [Rh2{(R)‐dosp}4] zur Vermittlung einer Sequenz aus Vinyldiazoacetat‐Cyclopropanierung und Cope‐Umlagerung liefert zwei diastereomere, enantiomerenangereicherte Cycloheptadiene, die den natürlichen Antipoden der Titel‐Diterpenoide entsprechen (siehe Schema).

magnified image
Is Cyanide Really a Strong‐Field Ligand?
Authors: Nakamura Mikio
Published: February 2009

Iron man or weakling? Ligand‐field strengths are conveniently expressed by the empirical spectrochemical series. Although cyanide has been deeply entrenched as a strong‐field ligand, a couple of recent examples cast doubt toward the position of this ligand, namely the high‐spin (S=2) states of [CrII(CN)5]3− and [FeII(tpp)(CN)]−. tpp=meso‐tetraphenylporphinate.

magnified image
Helical‐Ribbon Formation by a β‐Amino Acid Modified Amyloid β‐Peptide Fragment
Authors: Castelletto Valeria , Hamley Ian W. , Hule Rohan A. , Pochan Darrin
Published: February 2009

An addition to the family: The introduction of β‐amino acid residues into a modified amyloid β peptide fragment resulted in well‐defined helical nanoribbons (see cryo‐TEM image) comprising β strands mainly oriented perpendicular to the ribbon axis. The nanoribbons order into a flow‐aligning nematic phase at higher concentration. The β‐strand nanoribbon structure is an addition to the known set of secondary structures adopted by β‐peptides.

magnified image
From Ionic Liquids to Supramolecular Polymers
Authors: Craig Stephen L.
Published: February 2009

Charging forward: Ionic interactions presented in a multivalent fashion in small‐molecule ionic liquids lead to functional polymer‐like materials (see picture) that are consistent with the formation of a supramolecular ionic network. For example, the ionic material formed from a dication consisting of two covalently linked tetraalkyl phosphonium moieties and a porphyrin tetracarboxylate has a viscosity of 106 Pa s at 25 °C.

magnified image
The Imidazopyridine Derivative JK184 Reveals Dual Roles for Microtubules in Hedgehog Signaling
Authors: Cupido Tommaso , Rack Paul G. , Firestone Ari J. , Hyman Joel M. , Han Kyuho , Sinha Surajit , Ocasio Cory A. , Chen James K.
Published: February 2009

Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation (see figure).

magnified image
Synthesis of Goethite by Separation of the Nucleation and Growth Processes of Ferrihydrite Nanoparticles Using Microfluidics
Authors: Abou‐Hassan Ali , Sandre Olivier , Neveu Sophie , Cabuil Valérie
Published: February 2009

Microfluidic synthesis is used to form nanoparticles by separate nucleation and growth processes using two microreactors (see picture) operating under different temperature and flow conditions. Ferrihydrite nanoparticles precipitated in the first microreactor are aged under continuous flow in a second microtubular reactor, leading to goethite nanoparticles. TMAOH=tetramethylammonium hydroxide.

magnified image
Photoprogrammable Organic Light‐Emitting Diodes
Authors: Zacharias Philipp , Gather Malte C. , Köhnen Anne , Rehmann Nina , Meerholz Klaus
Published: February 2009

Enlightening the memory: The integration of a crosslinkable photochromic dithienylperfluorocyclopentene (DTE) into organic light‐emitting diodes (OLED) allows for the individualization of the emissive area of the OLED device, for example, for signage applications. The operation principle is based on switching the injection barrier for holes (positive charge carriers). Very large ON/OFF ratios of up to 3000 for current as well as electroluminescence have been achieved.

magnified image
Icosahedral DNA Nanocapsules by Modular Assembly
Authors: Bhatia Dhiraj , Mehtab Shabana , Krishnan Ramya , Indi Shantinath S. , Basu Atanu , Krishnan Yamuna
Published: February 2009

It's a trap! DNA polyhedra formed through molecular self‐assembly may function as nanocapsules for the targeted delivery of encapsulated entities. This functional aspect was demonstrated for the most complex DNA‐based platonic solid: During the stepwise amalgamation of discrete polyhedra to form icosahedra, gold nanoparticles (GNPs) were encapsulated from solution (see illustration and TEM image of icosahedral cages containing GNPs).

magnified image
Highly Enantioselective Pictet–Spengler Reactions with α‐Ketoamide‐Derived Ketimines: Access to an Unusual Class of Quaternary α‐Amino Amides
Authors: Bou‐Hamdan Farhan R. , Leighton James L.
Published: February 2009

“Quat's” the story? N‐Aryl amides are effective directing/activating groups for chlorosilane Lewis acids. This aspect has been exploited for the development of the first simple and general method for the highly enantioselective Pictet–Spengler reaction of ketimines derived from α‐ketoamides leading to quaternary α‐amino acid derivatives (see scheme).

magnified image
Challenging the Metallocene Dominance in Actinide Chemistry with a Soft PNP Pincer Ligand: New Uranium Structures and Reactivity Patterns
Authors: Cantat Thibault , Graves Christopher R. , Scott Brian L. , Kiplinger Jaqueline L.
Published: February 2009

A soft embrace for U: Replacement of C5Me5 by the soft PNP pincer ligand is a successful strategy to promote new reactivities and support new structures for the actinide series (see picture, py–O=pyridine‐N‐oxide). The specific electronic and steric properties of the PNP ligand enable access to previously unreported structures not available for the C5Me5 ligand set and support not only low‐valent uranium but also the high‐valent uranium(VI) ion.

magnified image
Parallel Kinetic Resolution Approach to the Cyathane and Cyanthiwigin Diterpenes Using a Cyclopropanation/Cope Rearrangement
Authors: Miller Laura C. , Ndungu J. Maina , Sarpong Richmond
Published: February 2009

Parallel effort: Stereodivergent parallel kinetic resolution of a racemic mixture of dienes using Davies' [Rh2{(S)‐dosp}4] or [Rh2{(R)‐dosp}4] catalysts promotes a tandem vinyl diazoacetate cyclopropanation/Cope rearrangement sequence to afford two diastereomeric, enantioenriched cycloheptadienes, which correspond to the natural antipodes of the title diterpenoids (see scheme).

magnified image
Characteristic reactions of group 9 transition metal compounds in organic synthesis
Authors: Omae Iwao
Published: February 2009

Group 9 metal compounds in organic synthesis have two characteristic reactions. The first occurs because the group 9 metals have a high affinity to carbon–carbon or carbon–nitrogen π‐bonds. The first type of characteristic reactions in these group 9 metal compounds includes Pauson–Khand reactions, the Pauson–Khand‐type reactions ([2 + 2 + 1] cyclization), the other cyclizations and coupling reactions. The second occurs because the group 9 metals have a high affinity to carbonyl groups. The second type of characteristic reactions includes carbonylations such as hydroformylations, the carbonylations of methanol, amidocarbonylations and other carbonylations. The first characteristic reactions are applied for the synthesis of fine chemicals such as pharmaceuticals and agrochemicals. However, the second characteristic reactions are utilized not only for fine chemicals but also for important bulk commodity chemicals such as aldehydes, carboxylic acids and alcohols. Copyright © 2009 John Wiley & Sons, Ltd.
Business strategies for transitions towards sustainable systems
Authors: Loorbach Derk , van Bakel Janneke C. , Whiteman Gail , Rotmans Jan
Published: February 2009

This paper develops a strategic perspective for business to contribute to the innovation of societal systems. Sustainability issues at the level of societal sectors cannot be addressed by single organizations but need to be thought of as systemic challenges in which business, government and civil society each play different roles. Sustainability involves structural changes over longer periods of time, and requires co‐evolutionary changes in technology, economy, culture and organizational forms. We propose that the transition management framework offers a fruitful way to analyze such co‐evolutionary processes of social transformation and subsequently develop strategies to influence and accelerate such processes. We present the case of two firms working in this new context of transition management in The Netherlands. From these cases we conceptualize a more general approach for business to redefine and reframe the societal context in which it is operating and develop novel business strategies. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.
Green segmentation and environmental certification: insights from forest products
Authors: Thompson Derek W. , Anderson Roy C. , Hansen Eric N. , Kahle Lynn R.
Published: February 2009

Firms engage inenvironmental marketingin order to appeal toenvironmentally conscious consumers. Within the context of the forest product industry, this research uses data from two studies to empirically test whether a relationship exists between demographic/psychographic characteristics and reported environmentally conscious intentions. In both studies, the results indicate that the environmental marketing of certified/ecolabeled forest products appeals to a segment of environmentally conscious consumers. This appeal occurs for both a value‐added product (furniture) and a non‐value‐added product (plywood). Thus, there is support for the argument that environmental marketing to environmentally conscious consumers can result in ‘green segmentation’. Key findings from this study suggest that those consumers reporting the strongest preferences for environmentally certified forest products were more willing to pay a premium for certified products, more likely to display environmentally conscious behavior and more likely to perceive that green consumer purchases effectively benefit the environment. These characteristics were most common among females and those familiar with the concept of environmental certification. Copyright © 2009 John Wiley & Sons, Ltd and EPR Environment.
NO Formation by Neuronal NO‐Synthase can be Controlled by Ultrafast Electron Injection from a Nanotrigger
Authors: Beaumont Edward , Lambry Jean‐Christophe , Blanchard‐Desce Mireille , Martasek Pavel , Panda Satya P. , van Faassen Ernst E. H. , Brochon Jean‐Claude , Deprez Eric , Slama‐Schwok Anny
Published: February 2009

Synchronized catalysis in native enzyme: We used a photoactive nanotrigger (NT) to study the initial electron transfer to FAD in native neuronal NOS catalysis. Modeling and fluorescence spectroscopy showed that selective NT binding to NADPH sites is able to override Phe1395 regulation, thus permitting ultrafast injection of electrons into the protein electron pathway. That NT initiation of flavoenzyme catalysis led to the formation of NO is promising for time‐resolved X‐ray and other cellular applications.

magnified image

Nitric oxide synthases (NOSs) are unique flavohemoproteins with various roles in mammalian physiology. Constitutive NOS catalysis is initiated by fast hydride transfer from NADPH, followed by slower structural rearrangements. We used a photoactive nanotrigger (NT) to study the initial electron transfer to FAD in native neuronal NOS (nNOS) catalysis. Molecular modeling and fluorescence spectroscopy showed that selective NT binding to NADPH sites close to FAD is able to override Phe1395 regulation. Ultrafast injection of electrons into the protein electron pathway by NT photoactivation through the use of a femtosecond laser pulse is thus possible. We show that calmodulin, required for NO synthesis by constitutive NOS, strongly promotes intramolecular electron flow (6.2‐fold stimulation) by a mechanism involving proton transfer to the reduced FAD− site. Site‐directed mutagenesis using the S1176A and S1176T mutants of nNOS supports this hypothesis. The NT synchronized the initiation of flavoenzyme catalysis, leading to the formation of NO, as detected by EPR. This NT is thus promising for time‐resolved X‐ray and other cellular applications.
Discovery of Additional Members of the Tyrosine Aminomutase Enzyme Family and the Mutational Analysis of CmdF
Authors: Krug Daniel , Müller Rolf
Published: February 2009

Stereochemical antipoles: The myxobacteria Chondromyces crocatus and Myxococcus fulvus utilize tyrosine aminomutase (TAM) enzymes with opposite stereoselectivity to produce β‐Tyr building blocks, which are subsequently incorporated into potent secondary metabolites. The evolution of stereochemical preference within this expanding enzyme family is unexplored. Intriguingly, the mutation of one amino acid in the aminomutase CmdF from C. crocatus influences the enantiomeric excess of (R)‐β‐Tyr formation (see chromatograms).

magnified image

The tyrosine aminomutase (TAM) CmdF converts L‐Tyr preferentially to (R)‐β‐Tyr—a biosynthetic building block subsequently incorporated into the highly cytotoxic chondramides by the myxobacterium Chondromyces crocatus. Together with the similar enzymes SgcC4 from Streptomyces globisporus and MdpC4 from Actinomadura madurae, which preferentially produce (S)‐β‐Tyr, CmdF belongs to a novel 2,3‐aminomutase enzyme family closely related to the aromatic amino acid ammonia lyase. Although considerable insight into the underlying catalytic mechanism has been provided recently by structural and mechanistic studies, the key determinants of product specificity and stereochemical preference of TAM enzymes remain to be elucidated in detail. We report herein the discovery and heterologous expression of additional TAMs from prokaryotic sources. These studies reveal a high degree of evolutionary diversification within this expanding enzyme family. Attempts to genetically engineer CmdF to exhibit ammonia lyase‐type activity by the exchange of conserved sequence motifs were largely unsuccessful. However, the variation of a semiconserved glutamic acid residue was found to impact stereoselectivity. Replacement of this residue by lysine significantly increased the enantiomeric excess of (R)‐β‐Tyr from 69 to 97 % ee, while substitution with methionine promoted racemization. These results suggest that it should be possible to elucidate a mechanism for control of stereoselectivity in the TAM family by the application of directed evolution to CmdF. Furthermore, our findings indicate the potential to fine‐tune the catalytic properties of TAMs for their use as biocatalysts or in engineered biosynthetic pathways.
Investigation of the Substrate Specificity of Lacticin 481 Synthetase by Using Nonproteinogenic Amino Acids
Authors: Levengood Matthew R. , Kerwood Christopher C. , Chatterjee Champak , van der Donk Wilfred A.
Published: February 2009

One enzyme, many substrates. The substrate specificity of a lantibiotic biosynthetic enzyme, lacticin 481 synthetase, was probed by using synthetic prepeptides containing a variety of nonproteinogenic amino acids, including unnatural α‐amino acids, β‐amino acids, D‐amino acids, and peptoids.

magnified image

Lantibiotics are peptide antimicrobial compounds that are characterized by the thioether‐bridged amino acids lanthionine and methyllanthionine. For lacticin 481, these structures are installed in a two‐step post‐translational modification process by a bifunctional enzyme, lacticin 481 synthetase (LctM). LctM catalyzes the dehydration of Ser and Thr residues to generate dehydroalanine or dehydrobutyrine, respectively, and the subsequent intramolecular regio‐ and stereospecific Michael‐type addition of cysteines onto the dehydroamino acids. In this study, semisynthetic substrates containing nonproteinogenic amino acids were prepared by expressed protein ligation and [3+2]‐cycloaddition of azide and alkyne‐functionalized peptides. LctM demonstrated broad substrate specificity toward substrates containing β‐amino acids, D‐amino acids, and N‐alkyl amino acids (peptoids) in certain regions of its peptide substrate. These findings showcase its promise for use in lantibiotic and peptide‐engineering applications, whereby nonproteinogenic amino acids might impart improved stability or modulated biological activities. Furthermore, LctM permitted the incorporation of an alkyne‐containing amino acid that can be utilized for the site‐selective modification of mature lantibiotics and used in target identification.
Phosphorothioation of Oligonucleotides Strongly Influences the Inhibition of Bacterial (M.HhaI) and Human (Dnmt1) DNA Methyltransferases
Authors: Warncke Simon , Gégout Aline , Carell Thomas
Published: February 2009

Methyltransferase inhibitors: Short double‐stranded oligonucleotides that have a hemimethylated target sequence and 5‐fluoro‐2′‐deoxycytidine as a suicide inhibitor as well as their phosphorothioated analogues were tested for their ability to inhibit the bacterial methyltransferase M.HhaI and the human Dnmt1 in vitro.

magnified image

The cytidine analogue 5‐fluoro‐2′‐deoxycytidine (dCF) is a mechanism‐based inhibitor of DNA methyltransferases. We report the synthesis of short 18‐mer dsDNA oligomers containing a triple‐hemimethylated CpG motive as a recognition sequence for the human methyltransferase Dnmt1. The DNA strands carry within these CpG islands dCF building blocks that function as mechanism‐based inhibitors of the analyzed methyltransferases. In addition, we replaced the phosphodiester backbones at defined positions by phosphorothioates. These hypermodified DNA strands were investigated as inhibitors of the DNA methyltransferases M.HhaI and Dnmt1 in vitro. We could show that both methylases behave substantially differently in respect to the amount of DNA backbone modification.
Rational Design of a Minimal and Highly Enriched CYP102A1 Mutant Library with Improved Regio‐, Stereo‐ and Chemoselectivity
Authors: Seifert Alexander , Vomund Sandra , Grohmann Katrin , Kriening Sebastian , Urlacher Vlada B. , Laschat Sabine , Pleiss Jürgen
Published: February 2009

Monooxygenase mutants: A minimal and highly enriched CYP102A1 mutant library was constructed by combining five hydrophobic amino acids in two positions. The library was screened with four different terpene substrates. Eleven variants demonstrated either a strong shift or improved regio‐ or stereoselectivity during oxidation of at least one substrate as compared to CYP102A1 wild type.

magnified image

A minimal CYP102A1 mutant library of only 24 variants plus wild type was constructed by combining five hydrophobic amino acids (alanine, valine, phenylalanine, leucine and isoleucine) in two positions. Both positions are located close to the centre of the haem group. The first, position 87, has been shown to mediate substrate specificity and regioselectivity in CYP102A1. The second hotspot, position 328, was predicted to interact with all substrates during oxidation and has previously been identified by systematic analysis of 31 crystal structures and 6300 sequences of cytochrome P450 monooxygenases. By systematically altering the size of the side chains, a broad range of binding site shapes was generated. All variants were functionally expressed in E. coli. The library was screened with four terpene substrates geranylacetone, nerylacetone, (4R)‐limonene and (+)‐valencene. Only three variants showed no activity towards all four terpenes, while eleven variants demonstrated either a strong shift or improved regio‐ or stereoselectivity during oxidation of at least one substrate as compared to CYP102A1 wild type.
On the Initiation Mechanism of Syndiospecific Styrene Polymerization Catalyzed by Single‐Component ansa‐Lanthanidocenes
Authors: Perrin Lionel , Sarazin Yann , Kirillov Evgueni , Carpentier Jean‐François , Maron Laurent
Published: February 2009

Single‐site catalysts: Syndiospecific styrene polymerization promoted by single‐site ansa‐lanthanidocene catalysts proceeds selectively in a secondary (2,1) fashion, both at the initiation and propagation steps. The steric hindrance between the phenyl ring of the incoming styrene monomer and the ancillary ligands (Cp′, Flu′), induced by the change of either the bridge or the “active” R ligand in the catalyst precursor, is proposed to control the reactivity of the complexes (see scheme).

magnified image

The mechanism of the initiation step of styrene polymerization promoted by single‐component ansa‐lanthanidocene catalysts [{Cp′XMe2Flu′}Ln(R)(ether)n] (Cp′=C5H4; Flu′=9‐C13H8; X=C or Si; R=allyl=CH2CHCH2 or alkyl=CH2SiMe3; ether=THF or Et2O, n=0,1) has been studied from a combined experimental/theoretical perspective. First, detailed 13C NMR studies conducted on syndiotactic oligostyrenes prepared by chain‐growth polymerization with [{C5H4CMe2Flu′}Nd(η3‐1,3‐C3H3(SiMe3)2)]/Mg(nBu)2 (1:50) have shown that the insertion of styrene in these lanthanidocene systems proceeds selectively in a secondary (2,1) fashion, both at the initiation and propagation steps. Next, DFT studies of styrene insertion have been carried out on three model compounds, [{Cp′CMe2Flu′}Eu(η3‐allyl)(thf)] (I), [{Cp′SiMe2Flu′}Eu(η3‐allyl)(thf)] (II), and [{Cp′CMe2Flu′}Eu(η1‐CH2SiMe3)(thf)] (III), in order to rationalize the influence of the ansa bridge (CMe2 vs. SiMe2) and that of the “active” R ligand (η3‐allyl vs. η1‐CH2SiMe3), previously noticed in styrene polymerization experiments. Dissociation of the THF molecule in precursor I appears not to be a rate‐limiting step and proceeds readily. The steric hindrance between the phenyl ring of the incoming styrene monomer and the ancillary ligands (Cp′, Flu′), induced by the change of either the bridge or the “active” R ligand, is proposed to control the reactivity of the complexes. In all cases, orientation of the styrene phenyl ring toward the most sterically opened Cp′ ligand (as compared to Flu′) and 2,1‐insertion of styrene have been found to be the most thermodynamically and kinetically favorable pathway. Also, in all cases, insertion of the first styrene unit proceeds directly in the η3‐coordinated allyl group. The lack of activity of the ansa‐dimethylsilylene allyl complex and of the ansa‐isopropylidene alkyl complex appears to be mainly due to the thermodynamics of the insertion reaction rather than the height of the activation barrier.
A Chemoenzymatic Approach to Enantiomerically Pure Amines Using Dynamic Kinetic Resolution: Application to the Synthesis of Norsertraline
Authors: Thalén Lisa K. , Zhao Dongbo , Sortais Jean‐Baptiste , Paetzold Jens , Hoben Christine , Bäckvall Jan‐E.
Published: February 2009

Dynamic transformation: A racemization catalyst and the enzyme Candida antarctica lipase B (CALB) were combined in a one‐pot dynamic kinetic resolution (DKR) of primary amines, which were transformed to their corresponding amides in up to 95 % yield and >99 % ee. This chemoenzymatic DKR was also applied to the synthesis of norsertraline (see scheme).

magnified image

Racemization catalyst 5 c and the enzyme Candida antarctica lipase B were combined in a one‐pot dynamic kinetic resolution (DKR) of primary amines in which a wide range of amines were transformed to their corresponding amides in up to 95 % isolated yield and >99 % ee. The DKR protocol was applicable with either isopropyl acetate or dibenzyl carbonate as the acyl donor. In the latter case, release of the free amine from the carbamate products was carried out under very mild conditions. The racemization of (S)‐1‐phenylethylamine with several different Ru catalysts was also evaluated. Catalyst 5 c, of the Shvo type, was able to selectively racemize amines and was also compatible with the reaction conditions used for DKR. A racemization study of three different amines with varying electronic properties was also performed. Competitive racemization of a 1:1 mixture of the deuterated and non‐deuterated amine was carried out with 5 c and a primary kinetic isotope effect was observed for all three amines, providing support that the rate‐determining step is β‐hydride elimination. The chemoenzymatic DKR protocol was applied to the synthesis of norsertraline (16) by using a novel route starting from readily available 1,2,3,4‐tetrahydro‐1‐naphthylamine (1 o).
Responsive Metal Complexes: A Click‐Based “Allosteric Scorpionate” Complex Permits the Detection of a Biological Recognition Event by EPR/ENDOR Spectroscopy
Authors: Tamanini Emiliano , Rigby Stephen E. J. , Motevalli Majid , Todd Matthew H. , Watkinson Michael
Published: February 2009

Click to detect!Azamacrocyclic complexes with a triazole scorpion ligand may be easily assembled, as shown for a biotin‐functionalised cyclam derivative. Coordination of the triazole to the metal is perturbed by the binding of avidin to the pendant ligand (see scheme). This event can be sensitively detected with EPR and ENDOR spectroscopy, which confirm the loss of the axial triazole nitrogen donor upon avidin binding. This general strategy may have wide applications in imaging and therapeutics.

magnified image

Chemical sensing is a mature field, and many effective sensors for small anions and cations have been devised. Metal complexes have been used widely for this purpose, but there are fewer reports of their use in the detection of organic and biological analytes. To date metal complexes have been used in sensing via the direct displacement of a pre‐existing ligand by an analyte, or by an adventitious complementarity between the complex and analyte. These strategies do not permit a general approach to the sensing of biological molecules with metal complexes because of the demands to engineer molecular recognition into the complex architecture. We describe a fundamentally new approach to this field—the “allosteric scorpionate” metal complex. The binding partner of a biological analyte is attached to a scorpionate ligand on a metal complex, remote from the metal centre. Binding of the analyte causes a change in the primary coordination sphere at the metal, thereby revealing the presence of the biological molecule. We show that azamacrocyclic complexes with a triazole scorpion ligand may be easily assembled with the [3+2] Huisgens ‘click’ cycloaddition. We demonstrate the synthesis of a biotin‐functionalised cyclam derivative using this methodology. This, and our previously communicated zinc sensor, are to the best of our knowledge the first examples of a triazole being employed as a scorpion ligand on an azamacrocycle. Coordination by the triazole to the metal is perturbed by the binding of avidin to the pendant ligand. This event can be sensitively detected with EPR spectroscopy, and the details of the coordination change probed with ENDOR spectroscopy, confirming the loss of the axial triazole nitrogen donor upon binding to avidin. This represents the first metal complex where remote, ‘allosteric’ coordination of an analyte has been shown to cause a change in the primary coordination sphere of the metal. Since the synthesis is modular and straightforward, other biological ligands may easily be introduced, and the associated binding events may be probed.
D‐Fructose‐6‐phosphate Aldolase in Organic Synthesis: Cascade Chemical‐Enzymatic Preparation of Sugar‐Related Polyhydroxylated Compounds
Authors: Concia Alda Lisa , Lozano Carles , Castillo José A. , Parella Teodor , Joglar Jesús , Clapés Pere
Published: February 2009

D‐Fructose‐6‐phosphate aldolase (FSA) is a key biocatalyst for the alternative synthetic construction of biologically active products with known therapeutic and research interest or novel structures relevant to drug discovery. Novel aldol addition reactions of dihydroxyacetone and hydroxyacetone to a variety of aldehydes catalyzed by FSA are presented (see scheme).

magnified image

Novel aldol addition reactions of dihydroxyacetone (DHA) and hydroxyacetone (HA) to a variety of aldehydes catalyzed by D‐fructose‐6‐phosphate aldolase (FSA) are presented. In a chemical‐enzymatic cascade reaction approach, 1‐deoxynojirimycin and 1‐deoxymannojirimycin were synthesized starting from (R)‐ and (S)‐3‐(N‐Cbz‐amino)‐2‐hydroxypropanal, respectively. Furthermore, 1,4‐dideoxy‐1,4‐imino‐D‐arabinitol and 1,4,5‐trideoxy‐1,4‐imino‐D‐arabinitol were prepared from N‐Cbz‐glycinal. 1‐Deoxy‐D‐xylulose was also synthesized by using HA as the donor and either 2‐benzyloxyethanal or 2‐hydroxyethanal as acceptors. In both cases the enzymatic aldol addition reaction was fully stereoselective, but with 2‐hydroxyethanal 17 % of the epimeric product at C2, 1‐deoxy‐D‐erythro‐2‐pentulose, was observed due to enolization/epimerization during the isolation steps. It was also observed that D‐(−)‐threose is a good acceptor substrate for FSA, opening new synthetic possibilities for the preparation of important novel complex carbohydrate‐related compounds from aldoses. To illustrate this, 1‐deoxy‐D‐ido‐hept‐2‐ulose was obtained stereoselectively by the addition of HA to D‐(−)‐threose, catalyzed by FSA. It was found that the reaction performance depended strongly on the donor substrate, HA being the one that gave the best conversions to the aldol adduct. The examples presented in this work show the valuable synthetic potential of FSA for the construction of chiral complex polyhydroxylated sugar‐type structures.
Silver‐Ion‐Mediated DNAzyme Switch for the Ultrasensitive and Selective Colorimetric Detection of Aqueous Ag+ and Cysteine
Authors: Li Tao , Shi Lili , Wang Erkang , Dong Shaojun
Published: February 2009

Two states, two applications! An Ag+‐mediated DNAzyme switch has been designed to detect Ag+ and cysteine with high sensitivity and selectivity. In the closed state, Ag+ turns on the switch through the formation of cytosine–Ag+–cytosine base pairs, whereas adding cysteine turns off the open switch because it competitively binds to Ag+. This feature endows the DNAzyme switch with two sensing applications.

magnified image
Structure–Activity Relationships and Binding Mode in the Human Acetylcholinesterase Active Site of Pseudo‐Irreversible Inhibitors Related to Xanthostigmine
Authors: Rizzo Stefano , Cavalli Andrea , Ceccarini Luisa , Bartolini Manuela , Belluti Federica , Bisi Alessandra , Andrisano Vincenza , Recanatini Maurizio , Rampa Angela
Published: February 2009

Acetylcholinesterase inhibitors: We extended the AChE inhibitors SAR study to newly synthesized compounds based on the lead compound xantostigmine. Docking and molecular dynamics simulations were carried out to both define a new computational protocol, and to acquire a better understanding of the SAR data. These computations prompted us to evaluate two of the synthesized compounds as inhibitors of AChE‐induced Aβ aggregation.

magnified image

Structure–activity relationship studies on acetylcholinesterase (AChE) inhibitors were extended to newly synthesized compounds derived from the lead compound xantostigmine (1). The xanthone ring of compound 1 was replaced with several different scaffolds based on the benzopyran skeleton, linked to the tertiary amino nitrogen through an heptyloxy chain. These modifications resulted in 19 new compounds, most of them showing activity in the nanomolar–subnanomolar range. Docking and molecular dynamics simulations were carried out to both define a new computational protocol for the simulation of pseudo‐irreversibile AChE covalent inhibitors, and to acquire a better understanding of the structure–activity relationships of the present series of compounds. The results of this computational work prompted us to to evaluate the ability of compounds 5 and 13 to inhibit acetylcholinesterase‐induced Aβ aggregation.
Plasmon‐Resonance‐Based Generation of Cathodic Photocurrent at Electrodeposited Gold Nanoparticles Coated with TiO2 Films
Authors: Sakai Nobuyuki , Fujiwara Yusuke , Takahashi Yukina , Tatsuma Tetsu
Published: February 2009

Reversed photoresponse: Indium tin oxide (ITO)/Au nanoparticle (NP)/TiO2 electrodes (see picture) exhibit cathodic photocurrents and positive photopotentials under visible light, whereas ITO/TiO2/Au NP electrodes show an inverted response. This behavior indicates that electron transfer occurs from the plasmon‐excited Au NPs to the TiO2 film. An enhanced O2 photoreduction activity is found for ITO/Au NP/TiO2/Pt electrodes.

magnified image
Glucocorticoid‐mediated effects on metabolism are reversed by targeting 11 beta hydroxysteroid dehydrogenase type 1 in human skeletal muscle
Authors: Salehzadeh Firoozeh , Al‐Khalili Lubna , Kulkarni Sameer S , Wang Minghan , Lönnqvist Fredrik , Krook Anna
Published: February 2009

Background

Adipose tissue and liver play important roles in mediating the metabolic actions of glucocorticoids. However, the effects of glucocorticoids on glucose and lipid metabolism in skeletal muscle are not understood completely. Intracellular glucocorticoid action is dependent on 11 β‐hydroxysteroid dehydrogenase 1 (HSD1), an enzyme that converts cortisone to active cortisol.

Methods

We investigated the direct role of HSD1 in cultured primary human skeletal muscle cells using siRNA and pharmacological inhibitors of the enzyme. Primary human skeletal muscle cells were cultured in the presence of 0.5 µM cortisone or 0.5 µM cortisol for eight days. siRNA was utilized to reduce expression of either HSD1 or pyruvate dehydrogenase kinase (PDK) 4. Effects of pharmacological inhibitors of HSD1 were also studied.

Results

Exposure to cortisone or cortisol decreased basal glucose uptake and glucose incorporation into glycogen, but was without effect on the insulin‐stimulated response. Glucocorticoid exposure increased palmitate oxidation, as well as the expression of PDK4. siRNA‐mediated reduction or pharmacological inhibition of HSD1 prevented the effects of cortisone, but not cortisol, on metabolic responses. siRNA‐mediated reduction of PDK4 prevented the effect of cortisol to attenuate glycogen synthesis.

Conclusion

Targeted reduction or pharmacological inhibition of HSD1 in primary human skeletal muscle cells prevents the effects of cortisone, but not cortisol, on glucose metabolism and palmitate oxidation. Furthermore, the glucocorticoid‐mediated reductions in glucose metabolism are dependent on PDK4. Copyright © 2009 John Wiley & Sons, Ltd.
Adaptive forecasting of the EURIBOR swap term structure
Authors: Blaskowitz Oliver , Herwartz Helmut
Published: February 2009

In this paper we adopt a principal components analysis (PCA) to reduce the dimensionality of the term structure and employ autoregressive (AR) models to forecast principal components which, in turn, are used to forecast swap rates. Arguing in favour of structural variation, we propose data‐driven, adaptive model selection strategies based on the PCA/AR model. To evaluate ex ante forecasting performance for particular rates, distinct forecast features, such as mean squared errors, directional accuracy and directional forecast value, are considered. It turns out that, relative to benchmark models, the adaptive approach offers additional forecast accuracy in terms of directional accuracy and directional forecast value. Copyright © 2009 John Wiley & Sons, Ltd.
Facial identity and facial expression matching in 5–12‐year‐old children and adults
Authors: Karayanidis Frini , Kelly Megan , Chapman Prudence , Mayes Angela , Johnston Pat
Published: February 2009

Facial identity and facial expression matching tasks were completed by 5–12‐year‐old children and adults using stimuli extracted from the same set of normalized faces. Configural and feature processing were examined using speed and accuracy of responding and facial feature selection, respectively. Facial identity matching was slower than face expression matching for all age groups. Large age effects were found on both speed and accuracy of responding and feature use in both identity and expression matching tasks. Eye region preference was found on the facial identity task and mouth region preference on the facial expression task. Use of mouth region information for facial expression matching increased with age, whereas use of eye region information for facial identity matching peaked early. The feature use information suggests that the specific use of primary facial features to arrive at identity and emotion matching judgments matures across middle childhood. Copyright © 2009 John Wiley & Sons, Ltd.
Late Quaternary landscapes in Central Australia: sedimentary history and palaeoecology of Puritjarra rock shelter
Authors: Smith M. A.
Published: February 2009

Puritjarra rock shelter provides a long record of late Quaternary vegetation in the Australian arid zone. Analysis of the sedimentary history of this rock shelter is combined with reanalysis of charcoal and phytolith records to provide a first‐order picture of changing landscapes in western Central Australia. These show a landscape responding to increasing aridity from 45 ka with deflation of clay‐rich red palaeosols (<45 ka) and sharp declines in grassland and other vegetation at 40–36 ka, and at the beginning of the Last Glacial Maximum (LGM) (24 ka). Vegetation in the catchment of the rock shelter recovered after 15 ka with expansion of both acacia woodland and spinifex grasslands, registering stronger summer rainfall in the interior of the continent. By 8.3 ka re‐vegetation of local palaeosols and dunes had choked off sediment supply to the rock shelter and the character of the sediments changed abruptly. Poaceae values peaked at 5.8 ka, suggesting the early–mid Holocene climatic optimum in Central Australia is bracketed between 8.3 and 5.8 ka. Local vegetation was disrupted in the late Holocene with a sharp decline in Poaceae at 3.8 ka, coinciding with an abrupt intensification of ENSO. Local grasslands recovered over the next two millennia and by 1.5 ka the modern vegetation appears to have become established. Copyright © 2009 John Wiley & Sons, Ltd.
Assessment of antiradical potential of Calluna vulgaris (L.) Hull and its major flavonoid
Authors: Deliorman‐Orhan Didem , Şenol Sezer , Kartal Murat , Orhan Ilkay
Published: February 2009

BACKGROUND: Antioxidant capacity of the chloroform, ethyl acetate, n‐butanol and water fractions of the aerial parts of Calluna vulgaris (L.) Hull (Ericaceae) has been assessed in this study. Antioxidant capacity of the plant was screened by assays of 2,2‐diphenyl‐β‐picrylhydrazyl, superoxide anion and hydrogen peroxide scavenging, metal‐chelating activity and reducing power. Butylated hydroxyanisole was used as reference in all assays; ethylene diamine tetraacetic acid was also used as reference in the assay of metal‐chelating activity. Total phenolic contents of the fractions were determined by the Folin–Ciocalteu method.

RESULTS: Liquid chromatography/diode array detection/mass spectrometry was used for phytochemical identification of the fractions. Kaempferol‐3‐O‐β‐D‐galactoside was found to be the major constituent in the ethyl acetate fraction (37.1 ± 0.9%), followed by the n‐butanol fraction (4.6 ± 0.1%). High occurrence of antioxidant capacity, with the exception of metal‐chelating activity, was observed in the ethyl acetate and chloroform fractions as well as in kaempferol‐3‐O‐β‐D‐galactoside.

CONCLUSION: Calluna vulgaris and its major flavonoid, kaempferol‐3‐O‐β‐D‐galactoside, show high antioxidant capacity in various assays. As far as is known, this is the first report on antioxidant capacity of C. vulgaris and its major flavonoid. Copyright © 2009 Society of Chemical Industry