JOURNAL OF FOOD BIOCHEMISTRY, Issue 3 2000
OWSKI, ROMAN KOT
ABSTRACT Oligonucleotide primers designed to flank a 635 bp fragment of the gene encoding glyceraldehyde-3-phosphate dehydrogenase (gpd) from Araanita muscaria were used to amplify the corresponding gpd fragment from Amanita phalloides. The A. phalloides PCR product was cloned, sequenced and found to be 70 - 77% similar to the known basidiomycetes gpd genes within the exon part and 25 - 52% within the intron part. Based on these data, species-specific amplification was achieved using a pair of oligonucleotide primers complementary to the A. phalloides gpd intron sequences. These primers allowed the amplification of the corresponding gpd fragment from the A. phalloides but not from various other basidiomycetes, ascomycetes and human matrices. PCR amplification of the A. phalloides DNA gave the predicted PCR product of 284 bp. The created PCR system is an efficient tool for the specific, rapid and sensitive detection of A. phalloides mycelium and spores. [source]

A PROVENANCE STUDY OF THE GILGAMESH FRAGMENT FROM MEGIDDO

ARCHAEOMETRY, Issue 5 2009
Y. GOREN
A Late Bronze Age fragment of a clay cuneiform tablet with the Gilgamesh Epic was found in the 1950s on the surface at Megiddo. The presence of scribes in Megiddo is evident from the el-Amarna letters. This is the only first-class literary Mesopotamian text ever to be found in Canaan. The aim of the present study was to examine the origin of this tablet, by mineralogical and elemental methods. The petrographic and NAA results indicate that the tablet was not Mesopotamian, but was written in southern Israel. The implications of this result in view of the small corpus of scholarly cuneiform texts discovered in Egypt and the southern Levant in the second millennium bce are discussed. [source]

DAIDALOS AND IKAROS ON AN APULIAN FRAGMENT NEWLY ACQUIRED BY THE BRITISH MUSEUM

BULLETIN OF THE INSTITUTE OF CLASSICAL STUDIES, Issue 1 2009
SUSAN WOODFORD
First page of article [source]

PHILOSOPHY IN FRAGMENTS: CULTIVATING PHILOSOPHIC THINKING WITH THE PRESOCRATICS

METAPHILOSOPHY, Issue 5 2009
DANIEL SILVERMINTZ
Abstract: This article presents a strategy for introducing Presocratic thought to students in a manner that is both engaging and relevant. The first section addresses students' reactions to the claim that the Presocratics were the first philosophers. The second section considers how the fragmentary state of Presocratic thought does not hinder its comprehension. The third section proposes a classroom exercise for testing the scientific merits of each of the Presocratic theories. The final section proposes the use of a mock trial as a means of applying the materialist approach introduced by the Presocratics to contemporary debates about free will and determinism. [source]

Synthesis and Characterization of Hypervalent Organoantimony(III) Compounds Containing the [2-(Me2NCH2)C6H4]2Sb Fragment

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 9 2009
Laura M. Opris
Abstract Compounds containing the [2-(Me2NCH2)C6H4]2Sb moiety were prepared by using R2SbX [X = Cl (1), Br (2)] as starting materials. The reaction of 1 with Me3SiCH2MgCl gave the mixed alkyl,aryl stibine R2SbCH2SiMe3 (3). Reduction of 2 with Mg in thf followed by in situ air oxidation or treatment with S8 resulted in the isolation of (R2Sb)2E [E = O (4), S (5)]. Compound 5 is also formed from R2SbCl and Na2S. The reaction of 4 with [W(CO)5(thf)] gives the unexpected complex [(R2SbOH)W(CO)5] (6). The new compounds were investigated by IR, 1H, and 13C NMR spectroscopy, as well as by mass spectrometry. The structures of 3,6 were determined by single-crystal X-ray diffraction. For compounds 3,5, both nitrogen atoms from the pendant arms are involved in intramolecular N,Sb coordination, which results in distorted square-pyramidal (C,N)2SbC or (C,N)2SbE (E = O, S) cores. By contrast, in 6 only one nitrogen atom is strongly coordinated to the antimony center, whereas the second nitrogen atom is involved in N···H,O bonding. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Transition-Metal (MnII and CoII) Complexes with the Heteropolymolybdate Fragment [AsVMo9O33]7,: Crystal Structures, Electrochemical and Magnetic Properties

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 17 2007
Yanyan Yang
Abstract Two novel heteropolymolybdates, [(CH3)4N]8n[M(H2O)5]2n(H3O)2n[{M(H2O)5}2(MAsVMo9O33)2]n[M(H2O)4(MAsVMo9O33)2]n·20nH2O (M = Mn2+, 1; M = Co2+, 2), constructed from the new fragment (AsVMo9O33)7, and a transition metal have been synthesized in aqueous solution and characterized by elemental analysis, IR spectroscopy, thermal gravimetric analysis, and single-crystal X-ray diffraction. Structurally the title complexes resemble a sandwich-type complex because they involve the coordination of two transition metals to two [AsVMo9O33]7, fragments, which derive from the well-known B -, - Keggin structure. Compounds 1 and 2 exhibit a one-dimensional chain-like framework [M(H2O)4(MAsVMo9O33)2]8n, with isolated {[M(H2O)5]2(MAsVMo9O33)2}6, units residing among the chains. The magnetic properties of the two complexes were investigated to indicate typical antiferromagnetic interactions through the MnII,O,MnII bridge unit for complex 1 and the CoII,O,CoII bridge unit for complex 2. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

Synthesis of the L-Acid (C1,C18) Fragment of Pamamycin-593 and De- N -methylpamamycin-579

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 29 2008
Ayako Miura
Abstract The L-acid (C1,C18) fragment of pamamycin-593 and de- N -methylpamamycin-579, strong aerial mycelium-inducers of Streptomyces alboniger, was synthesized using a cis -selective iodoetherification and a nucleophilic addition of a cerium acetylide to an aldehyde as the key steps. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]

Molecular diagnosis of Phytophthora lateralis in trees, water, and foliage baits using multiplex polymerase chain reaction

FOREST PATHOLOGY, Issue 5 2001
L. M. Winton
A polymerase chain reaction (PCR)-based protocol for detection of Phytophthora lateralis in plant tissues and water is described. Base-pair (bp) deletions in both of the ribosomal DNA internal transcribed spacer (ITS) regions in P. lateralis were used to design complementary PCR primer sequences that amplify a 738 bp fragment only if P. lateralis DNA is present in the sample. Universal control primers based on conserved sequences of the nuclear ribosomal small subunit are included in a multiplexed reaction, providing an internal check on the procedure. The universal primers amplify an approximately 550 bp fragment that is common to plants, protists, and true fungi. The procedure reliably detects P. lateralis in cedar stem tissues and in roots. Positive reactions were obtained with as few as 200 P. lateralis zoospores in water. Diagnostic moléculaire par PCR multiplex pour détecter Phytophthora lateralis dans les arbres, l'eau et le feuillage utilisé comme piège Un protocole basé sur la PCR est décrit pour détecter Phytophthora lateralis dans les tissus végétaux et l'eau. Des délétions de paires de bases dans chacune des régions ITS de l'ADN ribosomal de P. lateralis ont été utilisées pour définir des amorces de PCR qui n'amplifient un fragment de 738 paires de bases que si l'ADN de P. lateralis est présent dans l'échantillon. Des amorces universelles basées sur des régions conservées de la petite sous-unité de l'ADN ribosomal nucléaire ont été incluses dans une réaction de PCR multiplex, fournissant ainsi un témoin interne de la réaction. Ces amorces universelles amplifient un fragment de 550 pb qui est commun aux plantes, aux protistes et aux champignons vrais. Ce protocole permet la détection de P. lateralis dans les tiges et dans les racines du Chamaecyparis. Des réactions positives ont été obtenues avec seulement 200 zoospores de P. lateralis dans l'eau. Molekulare Diagnose von Phytophthora lateralis in Bäumen, Wasser und als Köder benutzten Blättern mittels Multiplex-PCR Eine auf der PCR beruhende Methode zum Nachweis von Phytophthora lateralis in Pflanzengeweben und Wasser wird beschrieben. Deletionen in den beiden ITS Regionen der ribosomalen DNA von P. lateralis wurden zur Synthese von PCR-Primern ausgenutzt, die ein 738 Basenpaare langes Fragment nur dann amplifizieren, wenn P. lateralis in der Probe vorhanden ist. Universelle Primer, die konservierten Sequenzen der kleinen Unterheit der ribosomalen Kern-DNA entsprechen, wurden als interne Kontrollen in die Multiplex-PCR miteinbezogen. Diese Primer amplifizieren ein ungefähr 550 Basenpaare langes Fragment, das sowohl bei Pflanzen als auch bei Protisten und höheren Pilzen vorkommt. Mit der Methode liess sich P. lateralis im Stamm und in den Wurzeln von Lawsons Scheinzypresse verlässlich nachweisen. Für den Nachweis von P. lateralis im Wasser waren mindestens 200 Zoosporen nötig. [source]

A generalized higher order kernel energy approximation method

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2010
Stewart N. Weiss
Abstract We present a general mathematical model that can be used to improve almost all fragment-based methods for ab initio calculation of total molecular energy. Fragment-based methods of computing total molecular energy mathematically decompose a molecule into smaller fragments, quantum-mechanically compute the energies of single and multiple fragments, and then combine the computed fragment energies in some particular way to compute the total molecular energy. Because the kernel energy method (KEM) is a fragment-based method that has been used with much success on many biological molecules, our model is presented in the context of the KEM in particular. In this generalized model, the total energy is not based on sums of all possible double-, triple-, and quadruple-kernel interactions, but on the interactions of precisely those combinations of kernels that are connected in the mathematical graph that represents the fragmented molecule. This makes it possible to estimate total molecular energy with high accuracy and no superfluous computation and greatly extends the utility of the KEM and other fragment-based methods. We demonstrate the practicality and effectiveness of our model by presenting how it has been used on the yeast initiator tRNA molecule, ytRN (1YFG in the Protein Data Bank), with kernel computations using the Hartree-Fock equations with a limited basis of Gaussian STO-3G type. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]

A Nonfibrillar Form of the Fusogenic Prion Protein Fragment [118-135] Induces Apoptotic Cell Death in Rat Cortical Neurons

JOURNAL OF NEUROCHEMISTRY, Issue 6 2000
Thierry Pillot
Abstract: Neuronal loss is a salient feature of prion diseases.However, its cause and mechanism, particularly its relationship with theaccumulation and precipitation of the pathogenic, protease-resistant isoformPrPSc of the cellular prion protein PrPC, are still anenigma. Several studies suggest that neuronal loss could occur through aprocess of programmed cell death, which is consistent with the lack ofinflammation in these conditions. By analogy with the pathological eventsoccurring during the development of Alzheimer's disease, controversies stillexist regarding the relationship between amyloidogenesis, prion aggregation,and neuronal loss. We recently demonstrated that a prion protein fragment(118-135) displayed membrane-destabilizing properties and was able to induce,in a nonfibrillar form, the fusion of unilamellar liposomes. To unravel themechanism of prion protein neurotoxicity, we characterize the effects of thehuman Pr[118-135] peptide on rat cortical neurons. We demonstrate that lowconcentrations of the Pr[118-135] peptide, in a nonfibrillar form, induce atime- and dose- dependent apoptotic cell death, including caspase activation,DNA condensation, and fragmentation. This toxicity might involve oxidativestress, because antioxidant molecules, such as probucol and propyl gallate,protect neurons against prion peptide toxicity. By contrast, a nonfusogenicvariant Pr[118-135, 0°] peptide, which displays the same amino acidcomposition but several amino acid permutations, is not toxic to corticalneurons, which emphasizes the critical role of the fusogenic properties of theprion peptide in its neurotoxicity. Taken together, our results suggest thatthe interaction between the Pr[118-135] peptide and the plasma membrane ofneurons might represent an early event in a cascade leading toneurodegeneration. [source]

Identification of a 251-bp Fragment of the PAI-1 Gene Promoter That Mediates the Ethanol-Induced Suppression of PAI-1 Expression

ALCOHOLISM, Issue 5 2001
Hernan E. Grenett
Background: Moderate alcohol consumption reduces the risk for coronary heart disease. This cardioprotection may be due to ethanol enhancement of fibrinolysis. Fibrinolysis involves the interaction of plasminogen activators (PAs) and the plasminogen activator inhibitor type-1 (PAI-1). Factor(s) that decrease endothelial cell (EC) PAI-1 expression increase fibrinolysis and may decrease the risk for cardiovascular disease. Methods: Five promoter deletion fragments were generated from a 1.1-kb PAI-1 promoter fragment and ligated to a luciferase reporter gene. Cultured human umbilical vein endothelial cells (HUVECs) were transiently transfected with these PAI-1 deletion constructs. A 251-base pair (bp) fragment of the PAI-1 promoter, positions ,800 to ,549, was cloned upstream of a heterologous promoter/enhancer. ECs luciferase activity was measured in the absence/presence of 20 mM ethanol. Electrophoresis mobility shift assays were performed with nuclear extracts from untreated and ethanol-treated ECs using this 251-bp fragment. Results: Deletion analysis showed a region between position ,800 and ,549 mediated ethanol repression of luciferase activity. This 251-bp promoter fragment also repressed the activity of a heterologous promoter/enhancer in the presence of ethanol. Using the labeled 251-bp fragment, nuclear extracts from ethanol-treated ECs contained two inducible bands and one enhanced band. Non-ethanol treated nuclear extracts also contained a band that was not observed in ethanol-treated samples. Competition using 100-fold molar excess of unlabeled probe abolished these four bands. Conclusions: Repression of PAI-I gene transcription in cultured HUVECs exposed to ethanol may involve the interaction of several transcription factors with binding sites localized between positions ,800 and ,549 of the PAI-1 gene promoter. [source]

The genus Adriohydrobia (Hydrobiidae: Gastropoda): polytypic species or polymorphic populations?

JOURNAL OF ZOOLOGICAL SYSTEMATICS AND EVOLUTIONARY RESEARCH, Issue 4 2001
T. Wilke
In molluscs, the shell characters have historically played an important role in discrimination among species. However, because of the paucity, variability and degree of homoplasy of shell characters, their sole use for taxonomic and systematic studies is controversial in many groups. In the present paper the genus AdriohydrobiaRadoman, 1973 is used as a paradigm to test relationships of taxa that were considered to be species, mainly on the basis of the shell size variations. We tested whether the genus consists of several sympatric and polytypic species or a single species with polymorphic populations and whether the reported shell size differences, on which the description of three putative species is mainly based, are intrinsic or extrinsic. A fragment of the mitochondrial cytochrome oxidase I (COI) gene was used as an independent genetic marker. We found very little genetic variability in 40 specimens from four populations studied. The nucleotide-sequence diversity (,) within populations ranges from 0.0017 to 0.0056 and the nucleotide-sequence divergence (Dxy) between populations from 0.0018 to 0.0051. The phylogenetic network is very compact with two ,groups' of haplotypes that are separated by only two nucleotide positions. A plot of pairwise nucleotide differences against pairwise shell size differences did not reveal any distinct clusters and a Mantel test did not show any significant associations between the two matrices. Based on the very low genetic diversity, the lack of distinct clusters in the phylogenetic network and the lack of concordance between morphological and genetic differentiation it is concluded that only one species is involved, Adriohydrobia gagatinella. The previously reported morphogroups within Adriohydrobia are probably due to a discrete age structure in these population and/or due to the effect of trematode-induced gigantism. The observed genetic patterns in Adriohydrobia indicate a rapid population growth from an ancestral population of small evolutionary-effective size. The present study stresses the importance of testing species-level hypotheses based on shell characters using one or more independent markers. Die Gattung Adriohydrobia (Hydrobiidae: Gastropoda): polytypische Arten oder polymorphe Populationen? Schalenmerkmale spielen historisch eine wichtige Rolle bei der Bestimmung von Molluskenarten. Die alleinige Nutzung von Schalenmerkmalen für systematische und taxonomische Arbeiten ist jedoch in vielen Gruppen umstritten, da die relativ wenigen Schalenmerkmale oft sehr variabel und durch einen hohen Grad von Homoplasie gekennzeichnet sind. In der vorliegenden Arbeit wurde die Gattung AdriohydrobiaRadoman, 1973 als Fallbeispiel genutzt, um Beziehungen von Arten innerhalb einer Gattung zu untersuchen, die hauptsächlich anhand ihrer Schalengröße unterschieden werden. Es wurde getestet, ob die Gattung mehrere sympatrische und polytypische Arten oder nur eine Art mit polymorphen Populationen umfasst. Darüber hinaus wurde untersucht, ob die dokumentierten Unterschiede in der Schalenhöhe, auf welchen die Beschreibung der drei potentiellen Arten der Gattung hauptsächlich beruhte, intrinsisch oder extrinsisch sind. Als unabhängiger genetischer Marker wurde ein Fragment des mitochondrialen Gens für Cytochromoxidase I (COI) verwendet. Die untersuchten 40 Individuen von vier Populationen zeichneten sich durch eine nur sehr geringe genetische Variabilität aus. Die Nukleotidsequenz-Diversität (,) innerhalb der Populationen variiert zwischen 0.0017 und 0.0056; die Nukleotidsequenz-Divergenz (Dxy) zwischen den Populationen reicht von 0.0018 bi 0.0051. Das phylogenetische Netzwerk ist sehr kompakt und umfasst zwei ,Gruppen' von Haplotypen, welche durch nur zwei Nukleotidpositionen getrennt sind. Die graphische Darstellung von paarweisen Nukleotid-Differenzen gegen paarweise Gehäusegröße-Differenzen lässt keine diskreten Gruppen erkennen und ein Mantel-Test zeigt keine signifikanten Beziehungen zwischen den Matrices. Aufgrund der geringen genetischen Differenzierung, des Fehlens von diskreten Gruppen im phylogenetischen Netzwerk und des nicht-signifikanten Zusammenhanges von morphologischer and genetischer Differenzierung wird geschlussfolgert, dass nur eine Art involviert ist, Adriohydrobia gagatinella. Die in der Literatur dokumentierten Morpho-Gruppen beruhen vermutlich auf einer diskreten Altersstruktur in diesen Populationen und/oder auf den Auswirkungen von trematoden-induziertem Gigantismus. Die festgestellten genetischen Muster in Adriohydrobia lassen das schnelle Wachstum einer Stammpopulation von geringer evolutionär-effektiver Größe vermuten. Die vorliegende Studie ist ein Beispiel dafür, wie wichtig es sein kann, auf Schalenmerkmale beruhende Arthypothesen mit unabhängigen Markern zu verifizieren. [source]

Law and Literature in the Romantic Era: The Law's Fictions

LITERATURE COMPASS (ELECTRONIC), Issue 4 2006
Sue Chaplin
This essay examines the emerging ideological relation between literature and law in the Romantic era and the significance of this relation to modern Western conceptualisations of what constitutes ,law' and ,literature'. In particular, the article explores the problematics of juridical textuality in the Romantic period , the extent to which the law comes to be regarded as text, and seeks to set this within the context of developing conceptualisations of ,literature' as a juridically defined commodity. The modern understanding of ,literature' began to be shaped in the Romantic era by a juridical re-formulation of the relation between the author, the text, the reader and the publisher: creative, original writing ,,literature', becomes a commodity copyrighted to an author/publisher. This development is accompanied by the State's recognition of the growing cultural and political power of new and diverse textual forms in an era of the mass production and consumption of ,literature', and the article considers alongside the contemporaneous formulation of copyright regulations the draconian censorship of textual production in this period. With reference to diverse juridical and literary sources (Clara Reeve's The Progress of Romance, Blackstone's Commentaries, Bentham's Fragment on Government, Godwin's Enquiry and Caleb Williams, amongst others), I examine the extent to which these various phenomena reveal the subjection of textuality in the Romantic era to the modern force of law. [source]

Identification of Diverse Database Subsets using Property-Based and Fragment-Based Molecular Descriptions

MOLECULAR INFORMATICS, Issue 6 2002
Mark Ashton
Abstract This paper reports a comparison of calculated molecular properties and of 2D fragment bit-strings when used for the selection of structurally diverse subsets of a file of 44295 compounds. MaxMin dissimilarity-based selection and k -means cluster-based selection are used to select subsets containing between 1% and 20% of the file. Investigation of the numbers of bioactive molecules in the selected subsets suggest: that the MaxMin subsets are noticeably superior to the k -means subsets; that the property-based descriptors are marginally superior to the fragment-based descriptors; and that both approaches are noticeably superior to random selection. [source]

A Fragment-Based In,Situ Combinatorial Approach To Identify High-Affinity Ligands for Unknown Binding Sites,

ANGEWANDTE CHEMIE, Issue 33 2010
Sachin
In leitender Position: Die im Titel genannte Methode zur Identifizierung von Liganden ist besonders nützlich, wenn keine oder nur unvollständige strukturelle Informationen zur Bindungsstelle verfügbar sind. In einem Fragment-basierten Verfahren wird durch NMR-Experimente ein geeignetes Paar von Liganden ermittelt. Mit einem Rezeptor-vermittelten, kombinatorischen In-situ-Verfahren werden die Liganden anschließend verknüpft und so in eine neue hochaffine Leitstruktur überführt (siehe Bild). [source]

Trapping a Difluorocarbene,Platinum Fragment by Base Coordination,

ANGEWANDTE CHEMIE, Issue 25 2010
Sonia Martínez-Salvador Dipl.-Chem.
Ertappt! Der Nachweis von Difluorcarben-Platin-Intermediaten bei der säureinduzierten Spaltung von Pt-CF3 -Bindungen gelang durch das Abfangen einer basestabilisierten PtCF2 -Einheit (siehe Schema). Beim Angriff eines N-Nucleophils (py*) auf das hoch elektrophile und extrem reaktive Kohlenstoffatom des Difluorcarbens wird eine C-N-Bindung gebildet. [source]

Titelbild: Quadrannulene: A Nonclassical Fullerene Fragment (Angew. Chem.

ANGEWANDTE CHEMIE, Issue 2 2010
2/2010)
Das Quadrat kann wie ein Fünfeck eine Krümmung in aromatischen Molekülen induzieren. In ihrer Zuschrift auf S.,409,ff. beschreiben B.,T. King et,al. die Synthese eines [4]Circulens, einer Verbindung mit vier anellierten Benzenoidringen, die ein internes Quadrat bilden. Dieses stark gekrümmte, schalenförmige Quadrannulen ist erstaunlich stabil, was seine Radialennatur widerspiegelt. [source]

Quadrannulene: A Nonclassical Fullerene Fragment,

ANGEWANDTE CHEMIE, Issue 2 2010
Bharat
Es wird kurvig: Ein [4]Circulen (siehe Bild), das gegen O2, Licht, Hitze, Säuren und Basen stabil ist, wurde in fünf Stufen synthetisiert. Die Befunde lassen vermuten, dass das quadratische Circulenmotiv in stabilen Fullerenstrukturen vorkommen könnte. [source]

N-Heterocyclic Carbene Stabilized Digermanium(0),

ANGEWANDTE CHEMIE, Issue 51 2009
Anastas Sidiropoulos
Germanium und sonst nichts! Die Reduktion eines Addukts aus einem N-heterocyclischen Carben (NHC) und GeCl2 mit Magnesium(I)-Dimeren ergab eine dimere Verbindung (siehe Bild), die nach Strukturuntersuchungen und theoretischen Studien ein Singulett-Digermanium(0)-Fragment :GeGe: enthält, das dativ durch zwei NHC-Liganden koordiniert ist. [source]

Cholesterol Secosterol Adduction Inhibits the Misfolding of a Mutant Prion Protein Fragment that Induces Neurodegeneration,

ANGEWANDTE CHEMIE, Issue 50 2009
Johanna
Der Aldehyd ist entscheidend: Der Cholesterin-5,6-secosterinaldehyd Atheronal-B (siehe Struktur) hemmt vollständig die Fehlfaltung eines Prionfragments von dessen ,- in die ,-Form, wobei der Inhibitionsmechanismus die Adduktbildung mit dem Protein einschließt. Dieses Ergebnis führt zu einer neuen Sichtweise von Lipidaldehyd-induzierten Proteinfehlfaltungen und bietet ein vielversprechendes Molekülgerüst für die Entwicklung potenzieller Therapeutika gegen Prionenkrankheiten. [source]

Local Stone (A Fragment)

ARCHITECTURAL DESIGN, Issue 6 2007
Reinhold Martin
Abstract At a time when a wide range of building materials is available around the world, the decision to use locally sourced stone in India often extends beyond the pragmatic. As Reinhold Martin explains, a particular choice of stone can potentially set off a complex string of associations with geopolitical connotations. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Forest Fragment and Breeding Habitat Characteristics Explain Frog Diversity and Abundance in Singapore

BIOTROPICA, Issue 1 2010
David Bickford
ABSTRACT Habitat loss and fragmentation can have severe negative and irreversible effects on biodiversity. We investigated the effects of forest fragmentation on frog diversity in Singapore because of its high rates of deforestation and the demonstration that frogs are some of the most sensitive species to habitat degradation. We surveyed frog species in 12 forest fragments varying from 11 to 935 ha. We compared differences in species richness, abundance, and Shannon's index in relation to forest fragment size, connectivity (distance between fragments), and breeding habitat heterogeneity. A total of 20 species from 12 genera and five families were encountered in 12 fragments. Larger fragments and those closer to larger fragments had higher species richness. Abundance, however, was not correlated with forest area or connectivity, but we found fewer individual frogs in the larger fragments. We also found that breeding habitat heterogeneity best explained frog species diversity and abundance in forest fragments. Fragments with a high diversity of breeding habitats had more species. We found no evidence to suggest that abundance and diversity are strongly correlated, particularly in disturbed areas, but that breeding habitat heterogeneity is an under-appreciated factor that should be considered when prioritizing areas for anuran conservation. Enriching breeding habitat heterogeneity, creating corridors between fragments, and reforesting degraded areas are some of the most beneficial strategies for preserving urban frog biodiversity. [source]

Persisting Hyper-abundance of Leaf-cutting Ants (Atta spp.) at the Edge of an Old Atlantic Forest Fragment

BIOTROPICA, Issue 6 2009
Sebastian T. Meyer
ABSTRACT Leaf-cutting ants (LCAs) profoundly benefit from edge creation in Neotropical forests, where they act as a keystone species and disturbance agent. In view of their poorly explored population dynamics, the question arises whether high densities of LCAs are a transitional or a persisting phenomenon. We studied the temporal variation of LCA colony densities at the edge of the Brazilian Atlantic forest. At physically stable edges of an old forest fragment, densities of Atta cephalotes and Atta sexdens (11 and five times higher in a 50 m edge zone in comparison with the forest interior) persisted over a 4-yr interval (2001,2005) with no significant difference in densities between years. Species-specific per colony growth rates ranged from 12 to ,5 percent/yr, suggesting that populations were approximately at equilibrium. High rates of colony turnover (little less than 50% in 4 yr) indicated an average colony life span of about 7 yr,a life expectancy considerably lower than previous estimates for Atta colonies. Stable, hyper-abundant populations of LCAs accord with the constantly high availability of palatable pioneer vegetation (the preferred food source of LCAs) at forest edges and are expected to persist in time as long as forests are characterized by high edge to interior ratios, with potentially long-lasting consequences for the ecosystem. [source]

On-Chip Fragment-Based Approach for Discovery of High-Affinity Bivalent Inhibitors

CHEMBIOCHEM, Issue 5 2009
Isao Miyazaki
Abstract Covalent bonds not required: We describe a novel approach in which the concepts of fragment-based ligand discovery are combined with chemical array techniques to yield bivalent inhibitors. A pair of fragments is mixed and covalently attached to a glass slide by photolinking immobilization. The method does not require the compounds to have specific functional groups, and tedious steps for protein purification are avoided. Thus, the on-chip fragment-based approach is relatively simple and efficient for obtaining high-affinity ligands. [source]

Discovery of Mycobacterium Tuberculosis Protein Tyrosine Phosphatase A (MptpA) Inhibitors Based on Natural Products and a Fragment-Based Approach

CHEMBIOCHEM, Issue 10 2005
Michael Manger Dr.
Naturally inspired or fragment based. Mcyobacterium tuberculosis has two functional phosphatases, protein tyrosine phosphates A and B (MptpA and B), which are thought to mediate mycobacterial survival in the host. Here we describe the first inhibitors of MptpA (see scheme). Initial hits were identified in screening collections that were inspired by natural products and composed by fragment-based approach. [source]

Mapping the Druggable Allosteric Space of G-Protein Coupled Receptors: a Fragment-Based Molecular Dynamics Approach

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 3 2010
Anthony Ivetac
To address the problem of specificity in G-protein coupled receptor (GPCR) drug discovery, there has been tremendous recent interest in allosteric drugs that bind at sites topographically distinct from the orthosteric site. Unfortunately, structure-based drug design of allosteric GPCR ligands has been frustrated by the paucity of structural data for allosteric binding sites, making a strong case for predictive computational methods. In this work, we map the surfaces of the ,1 (,1AR) and ,2 (,2AR) adrenergic receptor structures to detect a series of five potentially druggable allosteric sites. We employ the FTMAP algorithm to identify ,hot spots' with affinity for a variety of organic probe molecules corresponding to drug fragments. Our work is distinguished by an ensemble-based approach, whereby we map diverse receptor conformations taken from molecular dynamics (MD) simulations totaling approximately 0.5 ,s. Our results reveal distinct pockets formed at both solvent-exposed and lipid-exposed cavities, which we interpret in light of experimental data and which may constitute novel targets for GPCR drug discovery. This mapping data can now serve to drive a combination of fragment-based and virtual screening approaches for the discovery of small molecules that bind at these sites and which may offer highly selective therapies. [source]

Structural and Biophysical Characterization of XIAP BIR3 G306E Mutant: Insights in Protein Dynamics and Application for Fragment-Based Drug Design

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 3 2009
Cathy D. Moore
Previous reports describe modulators of X-linked inhibitor of apoptosis (XIAP),caspase interaction designed from the AVPI N-terminal peptide sequence of second mitochondria-derived activator of caspase. A fragment-based drug design strategy was initiated to identify therapeutic non-peptidomimetic antagonists of X-linked inhibitor of apoptosis protein,protein interactions. Fragments that bind to the AVPI binding site of BIR3 (bacculoviral inhibitory repeat) were identified, and to further localize the fragment binding within the AVPI binding site, a point mutation was designed which alters the dynamics of flexible loops and blocks PI region of the binding cleft, thus enabling definition of weakly bound small molecules in the AV portion of the binding cleft. Nuclear magnetic resonance analysis confirmed the G306E mutation stabilizes the AV pocket. Biophysical characterization of the mutant confirms conformation change within the PI sub-pocket as evidenced by a significant diminishment in binding affinity of AVPI mimetics, yet the binding affinity of the smaller AV mimetics is maintained or slightly improved in the mutant compared with wild-type. Additional data from non-covalent mass spectrometry analysis shows enhanced binding of AV mimetics to the G306E mutant over the wild-type. The presented data outline a protein engineering strategy that allowed mapping of AV-replacements with better sensitivity and precision. [source]

Discovery and Design of Novel HSP90 Inhibitors Using Multiple Fragment-based Design Strategies

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 1 2007
Jeffrey R. Huth
The molecular chaperone HSP90 has been shown to facilitate cancer cell survival by stabilizing key proteins responsible for a malignant phenotype. We report here the results of parallel fragment-based drug design approaches in the design of novel HSP90 inhibitors. Initial aminopyrimidine leads were elaborated using high-throughput organic synthesis to yield nanomolar inhibitors of the enzyme. Second site leads were also identified which bound to HSP90 in two distinct conformations, an ,open' and ,closed' form. Intriguingly, linked fragment approaches targeting both of these conformations were successful in producing novel, micromolar inhibitors. Overall, this study shows that, with only a few fragment hits, multiple lead series can be generated for HSP90 due to the inherent flexibility of the active site. Thus, ample opportunities exist to use these lead series in the development of clinically useful HSP90 inhibitors for the treatment of cancers. [source]

ChemInform Abstract: A Convenient Synthesis of Heterocyclic Compounds Containing 11-Oxo-6,11,12,13-tetrahydrodibenzo[b,g][1,5]oxazonine Fragment.

CHEMINFORM, Issue 7 2010
Victor V. Potapov
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

ChemInform Abstract: Fragment-Based Discovery of JAK-2 Inhibitors.

CHEMINFORM, Issue 20 2009
Stephen Antonysamy
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]