MedWorm: Molecular Biology

Asymmetric synthesis of [small alpha],[small beta]-diamino acid derivatives with an aziridine-, azetidine- and [gamma]-lactone-skeleton via Mannich-type additions across [small alpha]-chloro-N-sulfinylimines

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06637H, PaperGert Callebaut, Sven Mangelinckx, Lorand Kiss, Reijo Sillanpaa, Ferenc Fulop, Norbert De KimpeNew chiral syn- and anti-[gamma]-chloro-[small alpha],[small beta]-diamino esters are formed in high yield and in excellent diastereomeric ratios via stereoselective Mannich-type reactions of N-(diphenylmethylene) glycine esters across a chiral [small alpha]-chloro-N-p-toluenesulfinylimine.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Trichlorosilane mediated asymmetric reductions of the C[double bond, length as m-dash]N bond

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06854K, PerspectiveSimon Jones, Christopher J. A. WarnerLewis base activated trichlorosilane mediated reduction of ketimines offers significant advantages as an alternative method for the synthesis of chiral amine building blocks.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Highly emissive hand-shaped [small pi]-conjugated alkynylpyrenes: Synthesis, structures, and photophysical properties

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06865F, PaperJian-Yong Hu, Xin-Long Ni, Xing Feng, Masanao Era, Mark R. J. Elsegood, Simon J. Teat, Takehiko YamatoThree hand-shaped, highly fluorescent and stable alkynylpyrenes were successfully designed and synthesized, which are promising candidates in OLED-like optoelectronic devices.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Switching between ring closed and open N-incorporated heterocycles with tuneable charges and modular reactivity based upon 5-(2-bromoethyl)phenanthridinium bromide

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06708K, PaperRoslyn Eadie, Craig Richmond, Samantha Moreton, Leroy Cronin5-(2-bromoethyl)phenanthridinium bromide undergoes a 3-step-one-pot cyclisation reaction with primary amines allowing the facile synthesis of a vast library of heterocycles.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Characterization of DcsC, a PLP-independent racemase involved in the biosynthesis of D-cycloserine

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06864H, PaperDavid Dietrich, Marco J. van Belkum, John C. VederasWe show that DcsC is a PLP-independent racemase that acts on O-ureidoserine. It is inhibited by cysteine-inactivating reagents such as Hg2+, iodoacetamide, and a substrate analogue bearing an epoxide.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

A highly diastereoselective three-component tandem 1,4-conjugated addition-cyclization reaction to multisubstituted pyrrolidines

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06760A, PaperXia Zhang, Jingjing Ji, Yingguang Zhu, Changcheng Jing, Ming Li, Wenhao HuThree-component reactions of diazoacetophenones with anilines and unsaturated ketoesters afford multisubstituted pyrrolidines in good yield with high diastereoselectivity.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Radical-mediated nitrile translocation as the key step in the stereoselective transformation of 2-(4-chloro-2-cyanobutyl)aziridines to methyl cis-(1-arylmethyl-4-phenylpiperidin-2-yl)acetates

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07062F, PaperKarel Vervisch, Matthias D'hooghe, Karl W. Tornroos, Norbert De KimpeNon-activated 2-(4-chloro-2-cyano-2-phenylbutyl)aziridines were used as building blocks for the stereoselective synthesis of novel cis-2-cyanomethyl-4-phenylpiperidines via a microwave-assisted aziridine to piperidine ring expansion followed by a radical-induced nitrile translocation through initial...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

High efficiency of superacid HF/SbF5 for the selective decrystallization/depolymerization of cellulose to glucose

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07143F, CommunicationAgnes Martin Mingot, Karine Vigier, Francois Jerome, SEBASTIEN THIBAUDEAUHerein, we show that superacid HF/SbF5 is able after polyprotonation to depolymerise selectively cellulose to water-soluble carbohydrates along with 68 wt% yield of glucose. This process is efficient at low...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Investigation of the electrophilic reactivity of the cytotoxic marine alkaloid discorhabdin B

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07090A, PaperCary Lam, Tanja Grkovic, Norrie Pearce, Brent R. CoppThe mechanisms of action of the cytotoxic marine pyrroloiminoquinone alkaloids the discorhabdins are unknown. We have determined that discorhabdin B acts as an electrophile towards biomimetic thiol nucleophiles leading to...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Hydrogen tunnelling influences the isomerisation of some small radicals of interstellar importance. A theoretical investigation.

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07102A, PaperTianfang Wang, John H BowieHydrogen atom isomerisations within five radical systems (i.e., CH3.NH /.CH2NH; CH3O./.CH2OH; .CH2SH / CH3S.; CH3CO2. / .CH2CO2H; and HOCH2CH2O. / HO.CHCH2OH) have been studied via quantum-mechanical hydrogen tunnelling through reaction...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

A heterotrimetallic Pd/Sm/Pd complex for asymmetric Friedel-Crafts alkylations of pyrroles with nitroalkenes

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB25074H, CommunicationGuoqi ZhangCatalytic asymmetric Friedel-Crafts alkylations of pyrroles and nitroalkenes were carried out by using a novel heterotrimetallic Pd/Sm/Pd catalyst based on a simple chiral ligand 1, to give the adducts with...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Chiral recognition of carbon nanoforms

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07159B, Emerging AreaEmilio M Perez, Nazario MartinThe selective recognition of chiral carbon nanoforms poses a fundamental challenge. New design principles must be devised to construct hosts capable of enantiodiscrimination between species in which chirality does not...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Tunnelling control of chemical reactions - The organic chemist's perspective

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07170C, Emerging AreaDavid Ley, Dennis Gerbig, Peter SchreinerEven though quantum mechanical tunnelling has been appearing recurrently mostly in theoretical studies that emphasize its decisive role for many chemical reactions, it still appears suspicious to most organic chemists....The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Recent advances in the stereoselective synthesis of carbohydrate 2-C-analogs

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06529K, PerspectiveJian Yin, Torsten LinkerA perspective summarizing recent syntheses of carbohydrate 2-C-analogs 1 by ring-opening of cyclopropanated sugars 3 and radical additions to glycals 2 is given.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Biological activity of Fe(III) aquo-complexes towards ferric chelate reductase (FCR)

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06754D, PaperRosa Escudero, Mar Gomez-Gallego, Santiago Romano, Israel Fernandez, Angel Gutierrez-Alonso, Miguel A. Sierra, Sandra Lopez-Rayo, Paloma Nadal, Juan J. LucenaFe(III)-aquo complexes derived from phenol polyaminocarboxylic acids are highly efficient towards the enzyme ferric chelate reductase (FCR) and show interesting structure-activity properties in the enzymatic reduction process.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Copper(I)-amine metallo-organocatalyzed synthesis of carbo- and heterocyclic systems

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06449A, PaperBenjamin Montaignac, Victor Ostlund, Maxime R. Vitale, Virgnie Ratovelomanana-Vidal, Veronique MicheletThe efficient and atom economical synthesis of 5-membered cyclic structures is achieved through the combination of aminocatalysis and metal catalysis (30 examples 51-96% yield including cyclopentanes, indanes, pyrrolidines and tetrahydrofuran).To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Highly efficient asymmetric Michael addition of aldehyde to nitrooleﬁn using perhydroindolic acid as a chiral organocatalyst

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB00003B, PaperLina Zhao, Jiefeng Shen, Delong Liu, Yangang Liu, Wanbin ZhangPerhydroindolic acids, the by-products of a trandolapril intermediate, were used as chiral organocatalysts in asymmetric Michael addition reactions of aldehydes to nitroolefins. These proline-type catalysts are unique for their rigid...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Facile Synthesis of 4-Substituted 3,4-Dihydrocoumarins via an Organocatalytic Double Decarboxylation Process

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB25075F, CommunicationJian WangOver the past few decades, natural products have proven to be useful small-molecule probes in medicinally community.1 A rapid access to small molecules that are guided by natural products appears...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Aminohydroxyacetone Synthons: Versatile Intermediates for the Organocatalytic Asymmetric Aldol Reaction

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07107J, PaperHiyoshizo Kotsuki, Yoshiyuki Komatsu, Riki Watanabe, Keiji NakanoA practical method for the synthesis of 1,3-aminohydroxyacetone synthons was developed, and their utility in the organocatalytic asymmetric aldol reaction was demonstrated in a short synthesis of aza-sugars.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Understanding Local Electrophilicity/Nucleophilicity Activation through a Single Reactivity Difference Index

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06943A, PaperLuis R. Domingo, Prof. Pratim K Chattaraj , Soma DuleyA local reactivity difference index Rk is shown to be able to predict the local electrophilic and/or nucleophilic activation within an organic molecule. Together with the electrophilic and/or nucleophilic behavior...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Molecular Design of Chiral Quaternary Ammonium Polymers for Asymmetric Catalysis Application

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06909A, PaperMd. Masud Parvez, Naoki Haraguchi, Shinichi ItsunoChiral polymers containing organocatalyst in their main-chain structure is an important tool for the asymmetric reactions. Reaction of quaternary ammonium halide and sodium sulfonate gives stable salt of quaternary ammonium...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Borondipyrromethene-derived Cu2+ sensing chemodosimeter for fast and selective detection

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06980F, PaperChunchang Zhao, peng feng, jian cao, xuezhe wang, yang yang, yulin zhang, jinxin zhang, yanfen zhangHere, we report a new Cu2+-selective fluorescent turn-on probe BODIPY-EP, in which the 2-pyridinecarboxylic acid is connected to a 6-hydroxyindole-based BODIPY platform through an ester linkage. The ester bond of...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Intramolecular reductive ketone-alkynoate coupling reaction promoted by ([small eta] 2-propene)titanium

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07049A, PaperChristian Schafer, Michel Miesch, Laurence MieschIntramolecular reductive coupling of cycloalkanones tethered to alkynoates in the presence of ([small eta]2-propene)titanium was successfully performed to provide hydroxy-esters in a diastereoselective manner. Subsequent lactonization afforded angularly fused unsaturated tricyclic...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Substituted Oxines Inhibit Endothelial Cell Proliferation And Angiogenesis

RSC - Organic Biomolecular Chemistry — Thu, 09 Feb 2012 21:25:43 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06978D, PaperShridhar Bhat, Joong Sup Shim, Feiran Zhang, Curtis Chong, Jun LiuTwo substituted oxines, nitroxoline (5) and 5-chloroquinolin-8-yl phenylcarbamate (22), were identified as hits in a high-throughput screen aimed at finding new anti-angiogenic agents. In a previous study, we have elucidated...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

NF-[small kappa]B as a potential therapeutic target in microbial diseases

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05335G, ReviewMariateresa Vitiello, Marilena Galdiero, Emiliana Finamore, Stefania Galdiero, Massimiliano GaldieroModulation of NF-[small kappa]B activation and its signaling pathway during microbial infections offer novel targets for antimicrobial therapies.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Bioinformatic and experimental fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05437J, PaperT. Eichhorn, S. Schloissnig, B. Hahn, A. Wendler, Rolf Mertens, W. D. Lehmann, R. L. Krauth-Siegel, T. EfferthThe anti-malarial artemisinin also exerts profound anti-cancer activity, but the mechanisms of action are incompletely understood. In the present investigation, we present a novel approach to identify artemisinin-interacting target proteins.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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Analysis of crucial factors resulting in microarray hybridization failure

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05300D, PaperTing Wei, Mike N. Pearson, Karen Armstrong, Dietmar Blohm, Jue LiuTarget structure was concluded the most crucial factor resulting in microarray failure by a process of elimination in comparison to other multiple factors simultaneously.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Mathematical modeling of the low and high affinity arabinose transport systems in Escherichia coli

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05352G, PaperNecmettin YildirimIn E.coli, arabinose transport from extracellular media is mediated by two genetically distinct transport systems. The model we developed predicts that the two transport systems complement each other and there is a range of extracellular arabinose concentrations at which this system is capable of showing bistability.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Proteomic analysis in clear cell renal cell carcinoma: identification of differentially expressed protein by 2-D DIGE

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05390J, PaperFrancesca Raimondo, Claudia Salemi, Clizia Chinello, Daniela Fumagalli, Lavinia Morosi, Francesco Rocco, Stefano Ferrero, Roberto Perego, Cristina Bianchi, Cecilia Sarto, Marina Pitto, Paolo Brambilla, Fulvio Magni2-D DIGE representation of 23 up- and 77 down-regulated proteins in RCC.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Exploring salivary proteomes in edentulous patients with type 2 diabetes

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05079J, PaperMichael B. Border, Sarah Schwartz, Jim Carlson, Christopher F. Dibble, Heidi Kohltfarber, Steven Offenbacher, John B. Buse, Sompop BencharitThe salivary proteomic analysis of edentulous subjects using label-free quantitative mass spectrometry proteomics reveals differential expression of salivary proteins between subjects with and without type 2 diabetes.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

A Highly Efficient Tree Structure for the Biosynthesis of Heparan Sulfate Accounts for the Commonly Observed Disaccharides and Suggests a Mechanism for Domain Synthesis

RSC - Mol. BioSyst. latest articles — Thu, 09 Feb 2012 21:25:42 +0100

Mol. BioSyst., 2012, Accepted ManuscriptDOI: 10.1039/C2MB25019E, PaperEdwin Yates, Timothy R RuddThe form of the biosynthetic pathway of the biologically and medically important polysaccharides heparan sulfate and the closely related heparin remain obscure despite significant progress characterising the biosynthetic machinery. Considering...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer

Molecular Carcinogenesis — Thu, 09 Feb 2012 21:17:58 +0100

AbstractPromoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array‐CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the pre...

AAV-Mediated Gene Therapy in Mouse Models of Recessive Retinal Degeneration.

Current Molecular Medicine — Thu, 09 Feb 2012 21:12:49 +0100

Authors: Pang JJ, Lei L, Dai X, Shi W, Liu X, Dinculescu A, McDowell JH Abstract In recent years, more and more mutant genes that cause retinal diseases have been detected. At the same time, many naturally occurring mouse models of retinal degeneration have also been found, which show similar changes to human retinal diseases. These, together with improved viral vector quality allow more and more traditionally incurable inherited retinal disorders to become potential candidates for gene therapy. Currently, the most common vehicle to deliver the therapeutic gene into target retinal cells is the adeno-associated viral vector (AAV). Following delivery to the immuno-priviledged subretinal space, AAV-vectors can efficiently target both retinal pigment epithelium and photoreceptor cells,...

Advanced QSAR studies on PPARδ ligands related to metabolic diseases

Journal of the Brazilian Chemical Society — Thu, 09 Feb 2012 17:45:36 +0100

PPARδ is a nuclear receptor that, when activated, regulates the metabolism of carbohydrates and lipids and is related to metabolic syndrome and type 2 diabetes. To understand the main interactions between ligands and PPARδ, we have constructed 2D and 3D QSAR models and compared them with HOMO, LUMO and electrostatic potential maps of the compounds studied, as well as docking results. All QSAR models showed good statistical parameters and prediction outcomes. The QSAR models were used to predict the biological activity of an external test set, and the predicted values are in good agreement with the experimental results. Furthermore, we employed all maps to evaluate the possible interactions between the ligands and PPARδ. These predictive QSAR models, along with the HOMO, LUMO and MEP map...

Grainy head and its target genes in epithelial morphogenesis and wound healing.

Current Topics in Developmental Biology — Thu, 09 Feb 2012 15:36:04 +0100

Authors: Wang S, Samakovlis C Abstract The Grainy head (Grh) family of transcription factors is characterized by a unique DNA-binding domain that binds to a conserved consensus sequence. Nematodes and flies have a single grh gene, whereas mice and humans have evolved three genes encoding Grainy head-like (Grhl) factors. We review the biological function of Grh in different animals and the mechanisms modulating its activity. grh and grhl genes play a remarkably conserved role in epithelial organ development and extracellular barrier repair after tissue damage. Recent studies in flies and vertebrates suggest that Grh factors may be primary determinants of cell adhesion and epithelial tissue formation. Grh proteins can dimerize and act as activators or repressors in different developm...

Groucho a corepressor with instructive roles in development.

Current Topics in Developmental Biology — Thu, 09 Feb 2012 15:36:04 +0100

Authors: Turki-Judeh W, Courey AJ Abstract Drosophila Groucho (Gro) is the founding member of a family of metazoan corepressors. Gro mediates repression through interactions with a myriad of DNA-binding repressor proteins to direct the silencing of genes involved in many developmental processes, including neurogenesis and patterning of the main body axis, as well as receptor tyrosine kinase/Ras/MAPK, Notch, Wingless (Wg)/Wnt, and Decapentaplegic (Dpp) signaling. Gro mediates repression by multiple molecular mechanisms, depending on the regulatory context. Because Gro is a broadly expressed nuclear factor, whereas its repressor partners display restricted temporal and spatial distribution, it was presumed that this corepressor played permissive rather than instructive roles in devel...

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A dynamic network of morphogens and transcription factors patterns the fly leg.

Current Topics in Developmental Biology — Thu, 09 Feb 2012 15:36:04 +0100

Authors: Estella C, Voutev R, Mann RS Abstract Animal appendages require a proximodistal (PD) axis, which forms orthogonally from the two main body axes, anteroposterior and dorsoventral. In this review, we discuss recent advances that begin to provide insights into the molecular mechanisms controlling PD axis formation in the Drosophila leg. In this case, two morphogens, Wingless (Wg) and Decapentaplegic (Dpp), initiate a genetic cascade that, together with growth of the leg imaginal disc, establishes the PD axis. The analysis of cis-regulatory modules (CRMs) that control the expression of genes at different positions along the PD axis has been particularly valuable in dissecting this complex process. From these experiments, it appears that only one concentration of Wg and Dpp are...

Transcriptional control of cell fate specification lessons from the fly retina.

Current Topics in Developmental Biology — Thu, 09 Feb 2012 15:36:04 +0100

Authors: Quan XJ, Ramaekers A, Hassan BA Abstract It is now widely recognized that as cells of developing tissues transition through successive states of decreasing pluripotency into a state of terminal differentiation, they undergo significant changes in their gene expression profiles. Interestingly, these successive states of increasing differentiation are marked by the spatially and temporally restricted expression of sets of transcription factors. Each wave of transcription factors not only signals the arrival of a given stage in cellular differentiation, but it is also necessary for the activation of the next set of transcription factors, creating the appearance of a smooth, directed, and deterministic genetic program of cellular differentiation. Until recently, however, it wa...

Development of small-molecule probes that selectively kill cells induced to express mutant RAS.

Bioorganic and Medicinal Chemistry Letters — Thu, 09 Feb 2012 15:20:29 +0100

Authors: Weïwer M, Bittker JA, Lewis TA, Shimada K, Yang WS, Macpherson L, Dandapani S, Palmer M, Stockwell BR, Schreiber SL, Munoz B Abstract Synthetic lethal screening is a chemical biology approach to identify small molecules that selectively kill oncogene-expressing cell lines with the goal of identifying pathways that provide specific targets against cancer cells. We performed a high-throughput screen of 303,282 compounds from the National Institutes of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) against immortalized BJ fibroblasts expressing HRAS(G12V) followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRAS(G12V) oncogene. This effort led to the identification of two novel molecular probes (PubChem CID 3689413, ML16...

Human Biological Monitoring of Diisononyl Phthalate and Diisodecyl Phthalate: A Review

Advances in Urology — Thu, 09 Feb 2012 12:58:14 +0100

High molecular-weight phthalates, such as diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP), are widely used as plasticizers in the manufacturing of polymers and consumer products. Human biological monitoring studies have employed the metabolites of DINP and DIDP as biomarkers to assess human exposure. In this review, we summarize and analyze publicly available scientific data on chemistry, metabolism, and excretion kinetics, of DINP and DIDP, to identify specific and sensitive metabolites. Human biological monitoring data on DINP and DIDP are scrutinised to assess the suitability of these metabolites as biomarkers of exposure. Results from studies carried out in animals and humans indicate that phthalates are metabolised rapidly and do not bioaccmulate. During Phase-I metabolis...

Effect of Surface Architecture on In Vivo Ultrasound Contrast Persistence of Targeted Size-Selected Microbubbles

Ultrasound in Medicine and Biology — Thu, 09 Feb 2012 08:13:48 +0100

Abstract: Ultrasound molecular imaging is a powerful diagnostic modality using microbubbles coated with targeting ligands specific for endothelial biomarkers. The circulation persistence of ligand-bearing contrast agents is a key determinant in their contrast enhancement and targeting capability. Prior studies have shown that targeted microbubbles with ligands attached to the shell using the conventional exposed-ligand architecture (ELA) could trigger undesired ligand-induced complement activation and decreased circulation time. Microbubbles with the buried-ligand architecture (BLA), however, were found to inhibit complement activation and prolong circulation time. In the present study, we extended the stealth BLA microbubble design to size-selected (4 to 5-μm diameter) microbubbles targe...

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A new view to intracellular pathogens and host responses in the South of Spain

EMBO Molecular Medicine — Thu, 09 Feb 2012 05:00:00 +0100

Discussion on these topics provided new insights into the biology of these pathogens and enriched the field with new ideas for understanding why colonization of the intracellular niche of eukaryotic cells is a preferred strategy used by important human pathogens. (Source: EMBO Molecular Medicine)

Integrin α4 impacts on differential adhesion of preadipocytes and stem cells on synthetic polymers

Journal of Tissue Engineering and Regenerative Medicine — Thu, 09 Feb 2012 05:00:00 +0100

AbstractStem cells represent an ideal cell source for tissue engineering and regenerative medicine, because they can be readily isolated, expanded, differentiated and transplanted. For stem cell‐based therapies, biomaterials are required to allow for a spatial distribution of the stem cells within a defined area in the body. In our recent studies, we analysed the interaction of a large panel of stem cell types with an array of biomaterials and demonstrated that a rational prediction of stem cell behaviour on a specific biomaterial is so far not possible. Interestingly, even ontogenetically related stem cell types, such as mesenchymal stem cells (MSCs), preadipocytes and dental pulp stem cells (DPSCs), exhibit distinct adhesion properties on the very same biomaterial surface. Therefore, w...

Mesenchymal stromal cells improve the osteogenic capabilities of mineralized agarose gels in a rat full‐thickness cranial defect model

Journal of Tissue Engineering and Regenerative Medicine — Thu, 09 Feb 2012 05:00:00 +0100

AbstractThe authors previously created HAp or CaCO3 formed on or in agarose gels (HAp and CaCO3 gels, respectively) as biocompatible and biodegradable bone graft materials. However, these gels have limitations for bone regeneration. Mesenchymal stromal cells (MSCs) have osteogenic potential and are considered useful for bone tissue engineering. The purpose of this study was to clarify the osteogenic abilities of MSCs loaded in HAp or CaCO3 gels (MSC/HAp and MSC/CaCO3 gels, respectively) using a rat cranial defect model compared to HAp and CaCO3 gels alone. HAp, CaCO3, MSC/Hap, and MSC/CaCO3 gels were prepared for in vivo analyses and implanted into full‐thickness bone defects created in the rat cranium. All samples were assessed radiologically and histologically at 4 and 8 weeks after ...

Omental grafting: a cell‐based therapy for blood vessel repair

Journal of Tissue Engineering and Regenerative Medicine — Wed, 08 Feb 2012 05:00:00 +0100

This study is the first to demonstrate that omentum can provide progenitor cells for repair, thus revealing a novel and naturally occurring source of vascular smooth muscle for use in cell‐based therapies. Furthermore, our data show that this system can be optimized with inducing factors, highlighting a more powerful therapeutic potential than that of its current clinical application. This is a paradigm‐setting concept that lays the foundation for the use of chemical genetics to enhance therapeutic outcomes in a myriad of fields. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Journal of Tissue Engineering and Regenerative Medicine)

Stimulation of peripheral Kappa opioid receptors inhibits inflammatory hyperalgesia via activation of the PI3Kgamma/AKT/nNOS/NO signaling pathway

Molecular Pain — Wed, 08 Feb 2012 05:00:00 +0100

Conclusions: The present study indicates that activation of peripheral KORs directly blocks inflammatory hyperalgesia through stimulation of the nNOS/NO signaling pathway which is probably stimulated by PI3Kgamma/AKT signaling. This study extends a previously study of our group suggesting that PI3Kgamma/AKT/nNOS/NO is an important analgesic pathway in primary nociceptive neurons. (Source: Molecular Pain)

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Towards a quantitative understanding of the MITF-PIAS3-STAT3 connection

BMC Systems Biology - Latest articles — Wed, 08 Feb 2012 05:00:00 +0100

Conclusions: We find that the experimentally observed crosstalk between MITF and STAT3 via PIAS3 in melanocytes is faithfully reproduced in our model, offering mechanistic explanations for this behaviour, as well as providing a scaffold for further studies of MITF signalling in melanoma. (Source: BMC Systems Biology - Latest articles)

Evolution of the intercontinental disjunctions in six continents in the Ampelopsis clade of the grape family (Vitaceae)

BMC Evolutionary Biology - Latest articles — Wed, 08 Feb 2012 05:00:00 +0100

Conclusions: The global disjunctions in the Ampelopsis clade are best explained by a diversification model of North American origin, two Laurasian migrations, one migration into South America, and two post-Gondwanan long-distance dispersals. These findings highlight the importance of both vicariance and long distance dispersal in shaping intercontinental disjunctions of flowering plants. (Source: BMC Evolutionary Biology - Latest articles)

Cytotoxic functions and susceptibility to apoptosis of human CD56bright NK cells differentiated in vitro from CD34+ hematopoietic progenitors

Cytometry Part A — Wed, 08 Feb 2012 05:00:00 +0100

AbstractCytotoxic functions and susceptibility to apoptosis are crucial aspects of NK cells suitable to counter cancer after infusion in oncologic patients. To test the feasibility and the usefulness of infusing in vitro generated NK cells, these two features were investigated in NK cells developed in vitro from CD34+ hematopoietic progenitors. Purified CD34+ cells were cultured for 15–30 days with FLT‐3 ligand (FLT3‐L) and IL‐15 with or without IL‐21. To induce terminal differentiation, NK cells were cultured for further 15 days with IL‐15, IL‐21, or their combination. A CD56dim/CD16+ NK subset, expressing high level of perforin, granzymes, and LFA‐1, appeared early in cultures with FLT3‐L, IL‐15, and IL‐21, but it quickly died, indicating its predisposition to apopt...

Inquiry‐based examination of chemical disruption of bacterial biofilms

Biochemistry and Molecular Biology Education — Wed, 08 Feb 2012 05:00:00 +0100

AbstractInquiry‐based instruction in the sciences has been demonstrated as a successful educational strategy to use for both high school and college science classrooms. As participants in the NSF Graduate STEM Fellows in K‐12 Education (GK‐12) Program, we were tasked with creating novel inquiry‐based activities for high school classrooms. As a way to introduce microbiology, molecular biology, ecology, and human health to students, we created a laboratory activity involving formation of biofilms composed of environmental bacteria from pond water and investigation into the resistance of these biofilms to antimicrobial agents. Two high schools participated in this study in different ways. Pike High School biology and advanced environmental science classrooms obtained pond water sample...

Book Review

Biochemistry and Molecular Biology Education — Wed, 08 Feb 2012 05:00:00 +0100

(Source: Biochemistry and Molecular Biology Education)

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The Drosophila melanogaster Genetic Reference Panel

Nature — Wed, 08 Feb 2012 05:00:00 +0100

Authors: Trudy F. C. Mackay, Stephen Richards, Eric A. Stone, Antonio Barbadilla, Julien F. Ayroles, Dianhui Zhu, Sònia Casillas, Yi Han, Michael M. Magwire, Julie M. Cridland, Mark F. Richardson, Robert R. H. Anholt, Maite Barrón, Crystal Bess, Kerstin Petra Blankenburg, Mary Anna Carbone, David Castellano, Lesley Chaboub, Laura Duncan, Zeke Harris, Mehwish Javaid, Joy Christina Jayaseelan, Shalini N. Jhangiani, Katherine W. Jordan, Fremiet Lara, Faye Lawrence, Sandra L. Lee, Pablo Librado, Raquel S. Linheiro, Richard F. Lyman, Aaron J. Mackey, Mala Munidasa, Donna Marie Muzny, Lynne Nazareth, Irene Newsham, Lora Perales, Ling-Ling Pu, Carson Qu, Miquel Ràmia, Jeffrey G. Reid, Stephanie M. Rollmann, Julio Rozas, Nehad Saada, Lavanya Turlapati, Kim C. Worley, Yuan-Qing Wu, A...

Electron tomographic analysis of synaptic ultrastructure

The Journal of Comparative Neurology — Wed, 08 Feb 2012 05:00:00 +0100

AbstractSynaptic function depends upon interactions among sets of proteins that assemble into complex supramolecular machines. Molecular biology, electrophysiology and live‐cell imaging studies have provided tantalizing glimpses into the inner workings of the synapse, but fundamental questions remain regarding the functional organization of these “nano‐machines.” Electron tomography reveals the internal structure of synapses in three dimensions with exceptional spatial resolution. Here we report results from an electron tomographic study of axospinous synapses in neocortex and hippocampus of the adult rat, based on aldehyde‐fixed material stabilized with tannic acid in lieu of postfixation with osmium tetroxide. Our results provide a new window into the structural basis of excita...

BioResearch Open Access launching in March 2012 from Mary Ann Liebert, Inc., publishers

EurekAlert! - Medicine and Health — Wed, 08 Feb 2012 05:00:00 +0100

(Mary Ann Liebert, Inc./Genetic Engineering News) BioResearch Open Access, a new bimonthly peer-reviewed open access journal, will launch in March 2012 by Mary Ann Liebert, Inc., publishers. The journal will provide a new rapid-publication forum for a broad range of scientific topics including but not limited to molecular and cellular biology, tissue engineering and biomaterials, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. (Source: EurekAlert! - Medicine and Health)

An orthotopic model of platinum-sensitive high grade serous fallopian tube carcinoma.

International Journal of Clinical and Experimental Pathology — Tue, 07 Feb 2012 13:36:02 +0100

Authors: Khabele D, Fadare O, Liu AY, Wilson AJ, Wass E, Osteen K, Crispens MA Abstract Fallopian tube carcinoma (FTCA) is a very rare cancer type, but may be a useful platform for investigating high grade serous tumors of the pelvis that originate from a serous tubal intraepithelial carcinoma (STIC) precursor. Metastatic tumors from a patient diagnosed with Stage IIIC high grade serous FTCA (P0) were transplanted via intraperitoneal (IP) injection into a small cohort of mice (passage, P1). Patient information was obtained from the medical record. Tumors were grown, harvested and re-implanted or archived through P3. The P3 cohort was treated with saline (n=8) or cisplatin, 5 mg/kg (n=8), weekly for 4 weeks. After sacrifice, tumors from each passage and treatment group were passaged...

Calcineurin/NFAT signalling inhibits myeloid haematopoiesis

EMBO Molecular Medicine — Tue, 07 Feb 2012 05:00:00 +0100

In conclusion, these results provide evidence that calcineurin/NFAT signalling negatively regulates myeloid lineage development. The finding that inhibition of NFAT enhances myeloid development provides a novel insight into understanding how the treatment with drugs targeting calcineurin/NFAT signalling influence the homeostasis of the innate immune system. (Source: EMBO Molecular Medicine)

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P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons

Molecular Pain — Tue, 07 Feb 2012 05:00:00 +0100

Conclusions: These results show that the P2X7R expression increases as rats age. In addition, P2X7Rs in SGCs exert inhibitory control on the P2X3R expression and function in sensory neurons of immature rats, just as observed in adult rats. Regulation of P2X7R expression is likely an effective way to control P2X3R activity and manage pain relief in infants. (Source: Molecular Pain)

MicroRNA‐1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma

Molecular Carcinogenesis — Tue, 07 Feb 2012 05:00:00 +0100

This study explores how the microRNA binding to the STR region affects ECRG2 expression in ESCC. Dual‐luciferase reporter assays were used to verify the effects of the four microRNAs (miR‐580, miR‐1182, miR‐1272, and miR‐1322) predicted to bind the STR region of the ECRG2 3′ untranslated region (UTR). The expression of identified effective microRNA was then analyzed in 44 paired ESCC and adjacent normal tissues and 402 case–controlled serum samples (divided into a discovery group and an independent validation group) by real‐time RT‐PCR assay. We found that only miR‐1322 could significantly down‐regulate the ECRG2 with TCA3 allele (P < 0.01), but it could not down‐regulate the ECRG2 with TCA4 allele significantly (P > 0.05). MiR‐1322 was also expresse...

The ORF5 of Grapevine virus A is involved in symptoms expression in Nicotiana benthamiana plants

Annals of Applied Biology — Tue, 07 Feb 2012 05:00:00 +0100

AbstractGrapevine virus A (GVA), a member of the genus Vitivirus which belongs to the family Flexiviridae, has a single‐stranded RNA genome of about 7.4 kb that comprises five open reading frames (ORFs). ORF5 encodes a small 10‐kDa protein (p10), which is believed to interact with nucleic acids and to suppress the plant's RNA‐silencing response. We obtained molecular and biological data indicating that ORF5‐encoded product, specifically its N‐terminus, affects the appearance of symptoms in Nicotiana benthamiana plants. The ORF5‐encoded products of the severe GR5 and the mild GTR1‐1 isolates were found to affect RNA silencing similarly in mesophyll cells of N. benthamiana, despite being involved in different expressions of symptoms on this host. (Source: Annals of Applied Bi...

Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination [Immunology]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

We report that cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT–antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option. (Source: Proceedings of the National Academy of Scien...

Functional evidence that a recently evolved Drosophila sperm-specific gene boosts sperm competition [Evolution]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

In many species, both morphological and molecular traits related to sex and reproduction evolve faster in males than in females. Ultimately, rapid male evolution relies on the acquisition of genetic variation associated with differential reproductive success. Many newly evolved genes are associated with novel functions that might enhance male fitness. However, functional evidence of the adaptive role of recently originated genes in males is still lacking. The Sperm dynein intermediate chain multigene family, which encodes a Sperm dynein intermediate chain presumably involved in sperm motility, originated from complex genetic rearrangements in the lineage that leads to Drosophila melanogaster within the last 5.4 million years since its split from Drosophila simulans. We deleted all the memb...

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Three differentiation states risk-stratify bladder cancer into distinct subtypes [Computer Sciences]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes,...

Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires [Chemistry]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in neurons by modulation of photo-induced electron transfer (PeT) from an electron donor through a synthetic molecular wire to a fluorophore. These dyes give bigger responses to voltage than electrochromic dyes, yet have much faster kinetics and much less added capacitance than existing sensors based on hydrophobic anions or voltage-sensitive ion channels. These features enable single-trial detection of synaptic and action potentials in cultured hippocampal neurons and intact leech ganglia. Voltage-d...

Molecular architecture of the multisubunit homotypic fusion and vacuole protein sorting (HOPS) tethering complex [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

Membrane fusion within the eukaryotic endomembrane system depends on the initial recognition of Rab GTPase on transport vesicles by multisubunit tethering complexes and subsequent coupling to SNARE-mediated fusion. The conserved vacuolar/lysosomal homotypic fusion and vacuole protein sorting (HOPS) tethering complex combines both activities. Here we present the overall structure of the fusion-active HOPS complex. Our data reveal a flexible ≈30-nm elongated seahorse-like structure, which can adopt contracted and elongated shapes. Surprisingly, both ends of the HOPS complex contain a Rab-binding subunit: Vps41 and Vps39. The large head contains in addition to Vps41 the SNARE-interacting Vps33, whereas Vps39 is found in the bulky tip of its tail. Vps11 and Vps18 connect head and tail. Our d...

Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

Heterotrimeric G proteins are critical signal-transducing molecules controlled by a complex network of regulators. GIV (a.k.a. Girdin) is a unique component of this network and a nonreceptor guanine nucleotide exchange factor (GEF) that functions via a signature motif. GIV's GEF motif is involved in the regulation of critical biological processes such as phosphoinositide 3 kinase (PI3K)-Akt signaling, actin cytoskeleton remodeling, cell migration, and cancer metastasis. Here we investigated how the GEF function of GIV affects the wiring of its signaling pathway to shape different biological responses. Using a structure-guided approach, we designed a battery of GIV mutants with different Gαi-binding and -activating properties and used it to dissect the specific impact of changes in GIV's G...

Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 07 Feb 2012 05:00:00 +0100

In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial “Trojan horses” integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s, Salmonella SopA and Escherichia coli NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleL has little similarity to those of eukaryotic E3s. However, both bac...

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Vitamin D, Thrombosis, and Hemostasis: More than Skin Deep

Seminars in Thrombosis and Hemostasis — Tue, 07 Feb 2012 05:00:00 +0100

Semin Thromb Hemost 2012; 38: 114-124DOI: 10.1055/s-0031-1300957Vitamin D3 deficiency is a highly prevalent condition worldwide. Clinically, vitamin D3 has a key role in calcium homeostasis and bone mineralization and has recently been implicated in the pathogenesis and/or progression of several acute and chronic illnesses, including cardiovascular disease (CVD). Accumulating evidence from observational, prospective studies suggests that low levels of serum 25-hydroxyvitamin D3 are independently associated with an increased risk of CVD events and death. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a cardiovascular role for the active metabolite of vitamin D3. 1-α,25-dihydroxyvitamin D3 regulates the...

Thrombin and Cancer: From Molecular Basis to Therapeutic Implications

Seminars in Thrombosis and Hemostasis — Tue, 07 Feb 2012 05:00:00 +0100

Semin Thromb Hemost 2012; 38: 95-101DOI: 10.1055/s-0031-1300955The relationship between cancer and thrombosis has been recognized for nearly 150 years. Although the mechanisms underlying this association are not completely understood, there are increasing evidences suggesting a pivotal role of thrombin in cancer biology. This review will focus on the most important pathways by which thrombin may affect cancer growth and dissemination. In addition, the potential role of congenital (i.e., hemophilia) and pharmaceutical (i.e., antithrombotic agents) anticoagulation in cancer incidence and survival will be investigated through the analysis of the published experimental and clinical studies.[...]Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals:Ta...

Role of Molecular Genetics in Hemophilia: From Diagnosis to Therapy

Seminars in Thrombosis and Hemostasis — Tue, 07 Feb 2012 05:00:00 +0100

This article reviews the applications of molecular genetics in hemophilia, in general, and how such techniques can be useful for optimizing patient care, in particular.[...]Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals:Table of contents | Abstract | Full text (Source: Seminars in Thrombosis and Hemostasis)

The dependence of [small alpha]-tocopheroxyl radical reduction by hydroxy-2,3-diarylxanthones on structure and micro-environment

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06612B, PaperPatrice Morliere, Larry K. Patterson, Clementina M. M. Santos, Artur M. S. Silva, Jean-Claude Maziere, Paulo Filipe, Ana Gomes, Eduarda Fernandes, M. Beatriz Q. Garcia, Rene SantusFour hydroxyl groups are required for the repair of [small alpha]-tocopheroxyl radical by hydroxy-2,3-diarylxanthones.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Synthesis of pyrrolyldipyrrinato BF2 complexes by oxidative nucleophilic substitution of boron dipyrromethene with pyrrole

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06689K, PaperMin Zhang, Erhong Hao, Jinyuan Zhou, Changjiang Yu, Guifeng Bai, Fengyun Wang, Lijuan JiaoPyrrolyldipyrrinato BF2 complexes have been synthesized via a direct oxidative nucleophilic substitution of the 3-hydrogen of BODIPY dyes by pyrrole.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Involvement of DNA binding domain in the cellular stability and importin affinity of NF-[small kappa]B component RelB

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07104E, PaperMasatoshi Takeiri, Kana Horie, Daisuke Takahashi, Mariko Watanabe, Ryoichi Horie, Siro Simizu, Kazuo UmezawaNF-[small kappa]B is a transcription factor for the immune activation and tissue stability, but excess activation of NF-[small kappa]B often causes inflammation and cancer. An NF-[small kappa]B component RelB is involved in B-cell...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Synthesis and Protein Binding Studies of a Peptide Fragment of Clathrin Assembly Protein AP180 Bearing an O-Linked b-N-Acetylglucosaminyl-6-phosphate Modification

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07139H, CommunicationRichard James Payne, Mark E Graham, Robin S Stone, Phillip J RobinsonA novel post-translational modification of threonine, b-N-acetylglucosaminyl-phosphate, was recently discovered on assembly protein AP180, a protein which plays a crucial role in clathrin coated vesicle formation in synaptic vesicle endocytosis...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Fused Ring Aziridines as a Facile Entry into Triazole Fused Tricyclic and Bicyclic Heterocycles

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07042A, PaperFang Fang, Megan Vogel, Jennifer V Hines, Stephen BergmeierThe intramolecular dipolar cycloaddition of an azide with an alkyne has provided a useful entry into triazole fused tricyclic heterocycles containing both the triazole ring and the oxazolidin-2-one ring system....The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Click Synthesized Dianthryl-TTFV: An Efficient Fluorescent Turn-On Probe for Transition Metal Ions

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06828A, CommunicationKarimulla Mulla, Prateek Dongare, David W Thompson, Yuming ZhaoTetrathiafulvalene vinylogue (TTFV) was functionalized with two anthryl fluorophores via Cu(I)-catalyzed alkyne-azide [3+2] cycloaddition, forming a dianthryl-TTFV hybrid to show fluorescent turn-on sensing behaviour for Cu2+, Fe2+, and Cd2+ ions...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

A nmr and computational study of smac mimics targeting both the bir2 and bir3 domains in xiap protein

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06979B, PaperDonatella Potenza, laura BelvisiIn this paper we report an extensive NMR analysis of small ligands (Smac mimics) complexed with different constructs of XIAP. The mimics-binding site of XIAP is known as the BIR3...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Tetrakis(methylimidazole) and tetrakis(methylimidazolium) calix[4]arenes: competitive anion binding and deprotonation

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07025A, PaperCharlotte E. Willans, Emma K Bullough, Marc A Little, Colin KilnerNeutral tetrakis(methylimidazole) (1) and the novel cationic tetrakis(methylimidazolium) (2) calixarenes have been prepared and their solid-state and solution behaviour examined. The neutral imidazole forms a mono-zwitterion at elevated temperature, a...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

A Computational Study of the Enantioselective Addition of n-BuLi to Benzaldehyde in the Presence of a Chiral Lithium N,P-Amide

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06910E, PaperSten O. Nilsson Lill, Per-Ola Norrby, Jurgen Grafenstein, Goran Hilmersson, Petra RonnholmIn the presence of a chiral lithium N,P amide, alkylation of benzaldehyde results in an enantioselective formation of 1-phenyl-pentanol. This stereoselective addition reaction has herein been studied using dispersion-corrected density...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Intramolecular Chiral Communication in Peptide-Dendron Hybrids

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07014F, CommunicationHui Shao, Nicholas A Bewick, Jon ParquetteThe conformational properties of a series of peptide-dendron hybrids progressively incorporating 1-4 dendritic side chains were investigated by circular dichroism. Although the presence of multiple adjacent dendrons along the peptide...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Solid-state supramolecular assemblies consisting of planar charged species

RSC - Organic Biomolecular Chemistry — Mon, 06 Feb 2012 21:20:53 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07059F, PaperYohei Haketa, Mayumi Takayama, Hiromitsu MaedaPyrrole-based [small pi]-conjugated anion-responsive molecules provided various planar anionic structures by complexation with halide anions, resulting in the formation of solid-state assemblies with planar counter cations and exhibiting various modes of...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

GENOCOP algorithm and hierarchical grid transformation for image warping of two dimensional gel eletrophoretic maps

RSC - Mol. BioSyst. latest articles — Mon, 06 Feb 2012 21:20:53 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05396A, PaperEmilio Marengo, Marina Cocchi, Marco Demartini, Elisa Robotti, Daniela Cecconi, Giorgio CalabreseHierarchical grid transformation is a powerful approach to SDS 2DPAGE maps warping. The numerical optimization of the warping procedure is a multivariate task that can be solved efficiently using Genetic algorithms for Numerical Optimization in COnstrained Problems (GENOCOP).To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease

RSC - Mol. BioSyst. latest articles — Mon, 06 Feb 2012 21:20:53 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05461B, PaperNing Sun, Jing Liang, Zhanar Abil, Huimin ZhaoThe first pair of TAL effector nucleases was created and optimized for efficient cleavage of human [small beta]-globin gene locus, which may be used in treatment of sickle cell disease.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Genetic screens for the control of influenza virus replication: from meta-analysis to drug discovery

RSC - Mol. BioSyst. latest articles — Mon, 06 Feb 2012 21:20:53 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05416G, PaperBenoit de Chassey, Laurene Meyniel-Schicklin, Anne Aublin-Gex, Patrice Andre, Vincent LotteauIntegration of genetic screens and protein interaction data provides a rationale to identify drug candidates against influenza virus.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Parallel Tracking of cAMP and PKA signaling dynamics in Living Cells with FRET-based Fluorescent Biosensors

RSC - Mol. BioSyst. latest articles — Mon, 06 Feb 2012 21:20:53 +0100

Mol. BioSyst., 2012, Accepted ManuscriptDOI: 10.1039/C2MB05514G, PaperNwe-Nwe Aye-Han, Michael D. Allen, Qiang Ni, Jin ZhangProper regulation of cellular functions relies upon a network of intricately interwoven signaling cascades in which multiple components must be tightly coordinated both spatially and temporally. To better understand how...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Identification of DNA-protein complexes using an improved, combined Western Blotting- Electrophoretic Mobility Shift Assay (EMSA) with a fluorescence imaging system

RSC - Mol. BioSyst. latest articles — Mon, 06 Feb 2012 21:20:53 +0100

Mol. BioSyst., 2012, Accepted ManuscriptDOI: 10.1039/C2MB05500G, MethodKlaus Deckmann, Florian Rorsch, Gerd Geisslinger, Sabine GroschElectrophoretic Mobility Shift Assays (EMSAs) are used to detect DNA-protein interactions. With this type of assay it is difficult to distinguish between specific and non-specific DNA-protein complexes or to define...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate

Molecular Carcinogenesis — Mon, 06 Feb 2012 21:13:12 +0100

This study represents the first use of RNAseq to analyze tumors from animals consuming dietary phenethyl isothiocyanate and to identify potential molecular signatures that may explain the cancer protective effect of this compound. © 2012 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis)

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The Molecular Mechanisms of the Hepatoprotective Effect of Gomisin A against Oxidative Stress and Inflammatory Response in Rats with Carbon Tetrachloride-Induced Acute Liver Injury.

Biological and Pharmaceutical Bulletin — Mon, 06 Feb 2012 19:48:04 +0100

Authors: Teraoka R, Shimada T, Aburada M Abstract Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl(4))-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl(4) markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatmen...

Proceedings of the 2011 World Molecular Imaging Congress, San Diego, CA, USA, September 7-10, 2011

Molecular Imaging and Biology — Mon, 06 Feb 2012 19:37:34 +0100

Content Type Journal ArticlePages 1-993DOI 10.1007/s11307-012-0543-5 Journal Molecular Imaging and BiologyOnline ISSN 1860-2002Print ISSN 1536-1632 (Source: Molecular Imaging and Biology)

Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutanone, a radiolytic product of palmitic acid, in human lymphoma U937 cells

Apoptosis — Mon, 06 Feb 2012 19:34:01 +0100

In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells. We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis induced by 2-DCB and PA was strongly prevented by an antioxidant, N-acetyl-l-cysteine. The treatment with 2-DCB and PA resulted in the loss of mitochondrial membrane potential, and Fas, caspase-8 and caspase-3 activation. Pretreatment with a pan-caspase inhibitor (z-VAD) significantly inhibited apoptosis induced by 2-DCB and PA. Moreover, 2-DCB and PA also induced Bax up-regulation, the reduction in Bcl-2 expression level, Bid cleavage and the release of cytochrome c from the mitochondria to...

GAS1 induces cell death through an intrinsic apoptotic pathway

Apoptosis — Mon, 06 Feb 2012 19:33:59 +0100

Abstract Growth Arrest Specific 1 (GAS1) is a protein expressed when cells are arrested and during development. When ectopically expressed, GAS1 induces cell arrest and apoptosis of different cell lines, and we have previously demonstrated that the apoptotic process set off by GAS1 is caused by its capacity inhibiting the GDNF-mediated intracellular survival signaling. In the present work, we have dissected the molecular pathway leading to cell death. We employed the SH-SY5Y human neuroblastoma cell line that expresses GAS1 when deprived of serum. We observed, as we have previously described, that the presence of GAS1 reduces RET phosphorylation and inhibits the activation of AKT. We have now determined that the presence of GAS1 also triggers the dephosphorylation of BAD, wh...

Annulus fibrosus tissue engineering using lamellar silk scaffolds

Journal of Tissue Engineering and Regenerative Medicine — Mon, 06 Feb 2012 05:00:00 +0100

In this study, two types of scaffold morphology formed from silk fibroin were investigated towards the goal of AF tissue restoration. The first design mimics the lamellar features of the IVD that are associated with the AF region. The second is a porous spongy scaffold that serves as a control. Toroidal scaffolds were formed from the lamellar and porous silk material systems to generate structures with an outer diameter of 8 mm, inner diameter of 3.5 mm and a height of 3 mm. The inter‐lamellar spacing in the lamellar scaffold was 150–250 µm and the average pore sizes in the porous scaffolds were 100–250 µm. The scaffolds were seeded with porcine AF cells and, after growth over defined time frames in vitro, histology, biochemical assays, mechanical testing and gene express...

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Optimal Percoll concentration facilitates flow cytometric analysis for annexin V/propidium iodine‐stained ischemic brain tissues

Cytometry Part A — Mon, 06 Feb 2012 05:00:00 +0100

AbstractWe sought to determine the optimal Percoll concentration for ischemic rat brain prepared for flow cytometric (FC) measurements. Animals were subjected to the right middle cerebral artery (MCA) occlusion, and were euthanized at 3, 12, 24, and 72 h after reperfusion onset. The brains were processed by different concentrations (unisolated, 20, 25, 30, or 40%) of Percoll and stained with annexin V/propidium iodine (PI). Ischemic brain damage was evaluated by FC analysis and image analysis for histologic sections. The relative susceptibility of different phenotypes of cells to necrotic and apoptotic damage were evaluated by the FC analyses for the immunohistochemistry, PI, and the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling (TUNEL)‐pr...

Flow cytometry in cancer stem cell analysis and separation

Cytometry Part A — Mon, 06 Feb 2012 05:00:00 +0100

AbstractIn recent years, a special type of cancer cell—the cancer stem cell (CSC)—has been identified and characterized for different tumors. CSCs may be responsible for the recurrence of a tumor following a primarily successful therapy and are thought to bear a high metastatic potential. For the development of efficient treatment strategies, the establishment of reliable methods for the identification and effective isolation of CSCs is imperative. Similar to their stem cell counterparts in bone marrow or small intestine, different cluster of differentiation surface antigens have been characterized, thus enabling researchers to identify them within the tumor bulk and to determine their degree of differentiation. In addition, functional properties characteristic of stem cells can be mea...

Immunological advantages of everolimus versus cyclosporin A in liver‐transplanted recipients, as revealed by polychromatic flow cytometry

Cytometry Part A — Mon, 06 Feb 2012 05:00:00 +0100

AbstractSeveral immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver‐transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)‐2 and interferon (IFN...

Molecular detection of Colletotrichum falcatum causing red rot disease of sugarcane (Saccharum officinarum) using a SCAR marker

Annals of Applied Biology — Mon, 06 Feb 2012 05:00:00 +0100

AbstractRed rot disease of sugarcane caused by Colletotrichum falcatum is one of the most destructive diseases of sugarcane (Saccharum officinarum) worldwide. The pathogen spreads primarily through infected sugarcane setts and hence the use of disease‐free planting materials is essential for preventing disease development in the field. In the present study a polymerase chain reaction (PCR) assay was developed for accurate and sensitive detection of C. falcatum in planting materials. Randomly amplified polymorphic DNA (RAPD) analysis identified a 566 bp PCR fragment that was specific to C. falcatum. The DNA sequence of this fragment was determined and used to design oligonucleotides amplifying a 442 bp sequence characterised amplified region (SCAR). The specificity of the SCAR primers was...

Molecular architecture of a multifunctional MCM complex

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

DNA replication is strictly regulated through a sequence of steps that involve many macromolecular protein complexes. One of them is the replicative helicase, which is required for initiation and elongation phases. A MCM helicase found as a prophage in the genome of Bacillus cereus is fused with a primase domain constituting an integrative arrangement of two essential activities for replication. We have isolated this helicase–primase complex (BcMCM) showing that it can bind DNA and displays not only helicase and primase but also DNA polymerase activity. Using single-particle electron microscopy and 3D reconstruction, we obtained structures of BcMCM using ATPS or ADP in the absence and presence of DNA. The complex depicts the typical hexameric ring shape. The dissection of the unwindi...

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Characterization of the 6-methyl isoxanthopterin (6-MI) base analog dimer, a spectroscopic probe for monitoring guanine base conformations at specific sites in nucleic acids

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

We here characterize local conformations of site-specifically placed pairs of guanine (G) residues in RNA and DNA, using 6-methyl isoxanthopterin (6-MI) as a conformational probe. 6-MI is a base analog of G and spectroscopic signals obtained from pairs of adjacent 6-MI residues reflect base–base interactions that are sensitive to the sequence context, local DNA conformation and solvent environment of the probe bases. CD signals show strong exciton coupling between stacked 6-MI bases in double-stranded (ds) DNA; this coupling is reduced in single-stranded (ss) DNA sequences. Solvent interactions reduce the fluorescence of the dimer probe more efficiently in ssDNA than dsDNA, while self-quenching between 6-MI bases is enhanced in dsDNA. 6-MI dimer probes closely resemble adjacent GG re...

Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

We have investigated the DNA-binding nature as well as the function of a putative Alba (Acetylation lowers binding affinity) family protein (PfAlba3) from Plasmodium falciparum. PfAlba3 possesses DNA-binding property like Alba family proteins. PfAlba3 binds to DNA sequence non-specifically at the minor groove and acetylation lowers its DNA-binding affinity. The protein is ubiquitously expressed in all the erythrocytic stages of P. falciparum and it exists predominantly in the acetylated form. PfAlba3 inhibits transcription in vitro by binding to DNA. Plasmodium falciparum Sir2 (PfSir2A), a nuclear localized deacetylase interacts with PfAlba3 and deacetylates the lysine residue of N-terminal peptide of PfAlba3 specific for DNA binding. PfAlba3 is localized with PfSir2A in the periphery of t...

Interaction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing premature termination codons (PTC). The strength of the NMD response appears to reflect multiple determinants on a target mRNA. We have previously reported that mRNAs containing PTCs in close proximity to the translation initiation codon (AUG-proximal PTCs) can substantially evade NMD. Here, we explore the mechanistic basis for this NMD resistance. We demonstrate that translation termination at an AUG-proximal PTC lacks the ribosome stalling that is evident in an NMD-sensitive PTC. This difference is associated with demonstrated interactions of the cytoplasmic poly(A)-binding protein 1, PABPC1, with the cap-binding complex subunit, eIF4G and the 40S recruitment factor eIF3 as ...

Opposing effects of DNA on proteolysis of a replication initiator

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

DNA replication initiation proteins (Reps) are subjected to degradation by cellular proteases. We investigated how the formation of nucleoprotein complex, involving Rep and a protease, affects Rep degradation. All known Escherichia coli AAA+ cytosolic proteases and the replication initiation protein TrfA of the broad-host-range plasmid RK2 were used. Our results revealed that DNA influences the degradation process and that the observed effects are opposite and protease specific. In the case of ClpXP and ClpYQ proteases, DNA abolishes proteolysis, while in the case of ClpAP and Lon proteases it stimulates the process. ClpX and ClpY cannot interact with DNA-bound TrfA, while the ClpAP and Lon activities are enhanced by the formation of nucleoprotein complexes involving both the protease and ...

Luminescent detection of DNA-binding proteins

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

Transcription factors play a central role in cell development, differentiation and growth in biological systems due to their ability to regulate gene expression by binding to specific DNA sequences within the nucleus. The dysregulation of transcription factor signaling has been implicated in the pathogenesis of a number of cancers, developmental disorders, inflammation and autoimmunity. There is thus a high demand for convenient high-throughput methodologies able to detect sequence-specific DNA-binding proteins and monitor their DNA-binding activities. Traditional approaches for protein detection include gel mobility shift assays, DNA footprinting and enzyme-linked immunosorbent assays (ELISAs) which tend to be tedious, time-consuming, and may necessitate the use of radiographic labeling. ...

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Design, Synthesis and Biological Evaluation of Noncovalent Inhibitors of Human CD38 NADase.

ChemMedChem — Mon, 06 Feb 2012 05:00:00 +0100

Authors: Zhou Y, Ting KY, Lam CM, Kwong AK, Xia J, Jin H, Liu Z, Zhang L, Cheung Lee H, Zhang L Abstract Shoot the messenger! CD38 is a multifunctional enzyme responsible for the generation of calcium ion messengers. A structural optimization was carried out to develop noncovalent CD38 inhibitors based on hit compound S125 (top) (IC(50) =86 μM). The best compound inhibited CD38 NADase with an IC(50) value of 4.7 μM (bottom). Molecular modeling was used to predict potentially important interactions between the inhibitor and enzyme. PMID: 22287152 [PubMed - in process] (Source: ChemMedChem)

Predator-prey interactions paradigm: a new tool for artificial intelligence

Adaptive Behavior — Mon, 06 Feb 2012 05:00:00 +0100

Predator–prey interactions are probably one of the key mechanisms for explaining the evolution of organisms in their ecosystems. Scientific fields relevant to understanding the mechanisms of these interactions are as diverse as evolutionary biology, behavioral ecology, ecomorphology, molecular biology, phylogeny, neurosciences, physiology, biomechanics, and robotics. The difficulty in understanding these mechanisms lies therefore (1) in the multi- and interdisciplinary nature of this issue, and (2) in keeping up with very rapid developments in various scientific fields. This Special Issue provides an interdisciplinary approach to predator–prey interactions to identify how phenotypic traits of both types of organisms interact and how each can act as a selective pressure on the e...

Analysis of Nε‐Ethyllysine in Human Plasma Proteins by Gas Chromatography–Negative Ion Chemical Ionization/Mass Spectrometry as a Biomarker for Exposure to Acetaldehyde and Alcohol

Alcoholism: Clinical and Experimental Research — Mon, 06 Feb 2012 05:00:00 +0100

ConclusionsThe method could be applied to molecular epidemiological studies to investigate possible associations between the NEL levels in human tissue proteins and human diseases associated with exposure to AA and alcohol. (Source: Alcoholism: Clinical and Experimental Research)

High rates of de novo 15q11q13 inversions in human spermatozoa

Molecular Cytogenetics — Mon, 06 Feb 2012 05:00:00 +0100

Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS) fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies.Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 re...

Enumerating metabolic pathways for the production of heterologous target chemicals in chassis organisms

BMC Systems Biology - Latest articles — Mon, 06 Feb 2012 05:00:00 +0100

Conclusions: We find the topological approach to be faster by several orders of magnitude than the steady state approach. Yet both methods are generally scalable in time with the number of pathways in the metabolic network. Therefore this work provides an efficient tool for pathway enumeration with direct application to biosynthetic pathway design. (Source: BMC Systems Biology - Latest articles)

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Acoustic structure of male loud-calls support molecular phylogeny of Sumatran and Javanese leaf monkeys (genus Presbytis)

BMC Evolutionary Biology - Latest articles — Mon, 06 Feb 2012 05:00:00 +0100

Conclusions: In this study we show, that as in crested gibbons, the acoustic structure of surili loud-calls is a reliable tool to distinguish between species and to verify phylogenetic relatedness and migration backgrounds of respective taxa. Since vocal production in other nonhuman primates show similar constraints, it is likely that an acoustic analysis of call structure can help to clarify taxonomic and phylogenetic relationships. (Source: BMC Evolutionary Biology - Latest articles)

Heart hormone helps shape fat metabolism

EurekAlert! - Biology — Mon, 06 Feb 2012 05:00:00 +0100

This study increases our understanding of fat tissue regulation and may lead to new therapies aimed at weight reduction. (Source: EurekAlert! - Biology)

A new species of bamboo-feeding plant lice found in Costa Rica

EurekAlert! - Biology — Mon, 06 Feb 2012 05:00:00 +0100

(Pensoft Publishers) Several periods of field work during 2008 have led to the discovery of a new species of bamboo-feeding plant lice in Costa Rica's high-altitude region Cerro de la Muerte. The discovery was made thanks to molecular data analysis of mitochondrial DNA. The collected records have also increased the overall knowledge of plant lice (one of the most dangerous agricultural pests worldwide) from the region with more that 20 percent. The study was published in the open-access journal ZooKeys. (Source: EurekAlert! - Biology)

Personalized therapy of lung cancer.

Onkologie — Mon, 06 Feb 2012 02:58:36 +0100

Authors: Thomas R, Wolf J Abstract The implementation of personalized approaches in the treatment of patients with non-small cell lung cancer (NSCLC) requires a precise understanding of tumor biology, a reorientation of clinical development with a strong focus on genetically stratified early phase 'proof of concept' trials, the availability of high-quality 'realtime' genetic diagnostics, and the establishment of networks for molecular screening of lung cancer patients. To achieve this goal, a close interaction between basic researchers, clinical scientists, molecular pathologists, and pharmaceutical companies is essential. We believe that this approach is worth the effort, since personalized therapy in lung cancer has the potential to substantially improve survival in an increasing...

Immunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes.

Clinical and Developmental Immunology — Sun, 05 Feb 2012 16:27:26 +0100

Authors: Ozkurede VU, Franchi L Abstract OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Allergy, Host Responses, Cancer, Type 1 diabetes and viruses, Metabolic diseases. SUMMARY: Autoinflammatory syndromes are disorders characterized by the hyperactivation of the innate immune system in the absence of microbial infection or autoantibody production. Some autoinflammatory syndromes are associated with recurrent episodes of fever and systemic inflammation that are caused by dysregulated activation of inflammasomes, molecular platforms responsible for the activation of caspase-1 and the production of interleukin (IL)-1β. In this review we will discuss the role of IL-1β and the inflammasomes in host defence and how mutations of two genes, NLRP3 and PYRIN, leads ...

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Molecular Biology of Diabetes, Part II

Springer Medicine titles — Sun, 05 Feb 2012 06:01:08 +0100

Insulin Action, Effects on Gene Expression and Regulation, and Glucose TransportThese comprehensive yet concise collections of articles by world experts survey the latest findings on the molecular biology of diabetes and insulin action and synthesize a coherent understanding of the subject. Topics include the etiology of type I and type II diabetes, molecular and cellular aspects of insulin action, and the mechanism of the insulin-stimulated glucose uptake. (Source: Springer Medicine titles)

Histone deacetylase inhibition in colorectal cancer cells reveals competing roles for members of the oncogenic miR‐17‐92 cluster

Molecular Carcinogenesis — Sun, 05 Feb 2012 05:00:00 +0100

This study examined the role of microRNAs (miRNAs) in mediating the chemo‐protective effects of HDIs, and explored functions of the oncogenic miR‐17‐92 cluster. The dysregulated miRNA expression observed in HT29 and HCT116 CRC cells could be epigenetically altered by butyrate, SAHA and TSA. These HDIs decreased expression of miR‐17‐92 cluster miRNAs (P < 0.05), with a corresponding increase in miR‐17‐92 target genes, including PTEN, BCL2L11, and CDKN1A (P < 0.05). The decrease in miR‐17‐92 expression may be partly responsible for the anti‐proliferative effects of HDIs, with introduction of miR‐17‐92 cluster miRNA mimics reversing this effect and decreasing levels of PTEN, BCL2L11, and CDKN1A (P < 0.05). The growth effects of HDIs may be mediated...

Synthesis of amine-functionalized heparin oligosaccharides for the investigation of carbohydrate-protein interactions in microtiter plates

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06607F, PaperSusana Maza, Giuseppe Macchione, Rafael Ojeda, Javier Lopez-Prados, Jesus Angulo, Jose L. de Paz, Pedro M. NietoA series of amine-functionalized heparin oligosaccharides were efficiently synthesized and attached to microplates for the qualitative and quantitative analysis of their interactions with proteins.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

N-Activated [small beta]-lactams as versatile reagents for acyl carrier protein labeling

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06846J, PaperGitanjeli Prasad, Jon W. Amoroso, Lawrence S. Borketey, Nathan A. SchnarrA series of reactive [small beta]-lactams have been prepared for direct labeling of holo-acyl carrier proteins in site-selective fashion.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

A New Synthetic Route for Axially Chiral Secondary Amines with Binaphthyl Backbone and Their Applications in Asymmetric Michael Reaction of Aldehydes to Nitroalkenes

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07110J, PaperDa-Cheng Liang, Ren-Shi Luo, Li-Hua Yin, Albert S. C. Chan, Gui LuA new synthetic route for binaphthyl-based secondary amines has been developed. The key feature of this route includes the selective direct esterification of the binaphthyl structure at the 3- or...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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A General Electron Transfer Reduction of Lactones Using SmI2-H2O

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB00017B, CommunicationMichal Szostak, Karl D Collins, Neal J Fazakerley, Malcolm Spain, David John ProcterHerein we describe a strategy for the selective, electron transfer reduction of lactones of all ring sizes and topologies using SmI2-H2O and a Lewis base to tune the redox properties...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Investigating the Reaction Mechanism and Organocatalytic Synthesis of [small alpha],[small alpha]'-Dihydroxy Ketones

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06939C, PaperHelen Hailes, James L Galman, David Steadman, Lisa D HaighA biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate [small alpha],[small alpha]'-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used....The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Mechanism of the alkali degradation of (6-4) photoproduct-containing DNA

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06966K, PaperNorihito Arichi, Aki Inase, Sachise Eto, Toshimi Mizukoshi, Junpei Yamamoto, Shigenori IwaiThe mechanism of the alkali-induced strand breaks caused at the (6-4) photoproduct sites in UV-irradiated DNA was elucidated.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Lipothiophosphoramidates for gene delivery: critical role of the cationic polar headgroup

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06812E, PaperAurore Fraix, Tristan Montier, Tony Le Gall, Charlotte M. Sevrain, Nathalie Carmoy, Mattias F. Lindberg, Pierre Lehn, Paul-Alain JaffresThe synthesis of cationic lipothiophosphoramidates possessing different cationic groups (ammonium, phosphonium or arsonium) is reported. Transfection experiments showed that the arsonium-containing lipid (Z+ = As+) is globally the most efficient on the three cell lines tested.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Studies on a novel class of triaryl pyridine N-glycosylamine amphiphiles as super gelators

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06834F, PaperManivannan Kalavathi Dhinakaran, Thangamuthu Mohan DasA novel class of six different triaryl pyridine N-glycosylamine amphiphiles was synthesised and characterized based on different spectral techniques, such as NMR and mass analysis. Gelation was observed predominantly in aliphatic solvents and is due to the presence of the alkyl chain. All the gels thus obtained were studied using powder XRD and FE-SEM techniques which reveal fibrous entanglement of the molecules in the gel state.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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The microbial cell factory

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06903B, PerspectiveCormac D. MurphyMicroorganisms are involved in many applications; this review outlines some of the contemporary products arising from manipulation of bacteria and fungi.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Insights into a surprising reaction: The microwave-assisted direct esterification of phosphinic acids

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06972E, PaperGyorgy Keglevich, Nora Zsuzsa Kiss, Zoltan Mucsi, Tamas KortvelyesiNew synthetic results and theoretical data including the thermodynamic and kinetic parameters are discussed for the direct esterification of phosphinic acids that is reluctant on heating, but takes place quantitatively on MW irradiation.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Fluorogenic sensing of CH3CO2- and H2PO4- by ditopic receptor through conformational change

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06994F, PaperNisar Ahmed, Vangaru Suresh, Bahareh Shirinfar, Inacrist Geronimo, Amita Bist, In-Chul Hwang, Kwang S. KimCyclo-bis-(urea-3,6-dichlorocarbazole) (1) forms a 1 : 2 complex with CH3CO2- and H2PO4- through hydrogen bonding with the two urea moieties, resulting in fluorescence enhancement via a combined photoinduced electron transfer (PET) and energy transfer mechanism.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Relaxation of the rigid backbone of an oligoamide-foldamer-based [small alpha]-helix mimetic: identification of potent Bcl-xL inhibitors

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB07125H, CommunicationJeremy Yap, Xiaobo Cao, Kenno Vanommeslaeghe, Kwan-Young Jung, Paul Wilder, anjan nan, Alex Mackerell, W Roy Smythe, Steven FletcherBy conducting a structure-activity relationship study of the backbone of a series of oligoamide-foldamer-based [small alpha]-helix mimetics of the Bak BH3 helix, we have identified especially potent inhibitors of Bcl-xL. The...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Using Light and a Molecular Switch to 'Lock' and 'Unlock" the Diels-Alder Reaction

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06908C, PaperZach Erno, Amir AsadiRad, Vincent Lemieux, Neil R. BrandaLight is used to 'gate' the Diels-Alder reaction using a photoresponsive dithienylfuran backbone and turn the reversibility of the Diels-Alder reaction 'off' and 'on' at 100 [degree]C. These features make...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Copper(I) Acetate-Catalyzed Azide-Alkyne Cycloaddition for Highly Efficient Preparation of 1-(Pyridin-2-yl)-1,2,3-Triazoles

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Accepted ManuscriptDOI: 10.1039/C2OB06942C, PaperQun Zhang, Xinyan Wang, Chuanjie Cheng, Rui Zhu, Nan Liu, Yuefei HuA highly efficient copper(I)-catalyzed azide-alkyne cycloaddition of 6-NO2 and 6-CO2Et substituted tetrazolo[1,5-a]pyridines was developed for the preparation of 1-(pyridin-2-yl)-1,2,3-triazoles by simply using copper(I) acetate as a catalyst. The in situ...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Efficient synthesis of carbazoles via PtCl2-catalyzed RT cyclization of 1-(indol-2-yl)-2,3-allenols: scope and mechanism

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C1OB06474F, PaperWangqing Kong, Chunling Fu, Shengming MaThe efficient PtCl2-catalyzed synthesis of carbazoles from 1-(indol-2-yl)-2,3-allenols through a unique metal carbene intermediate is described.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

2-Aminopyrimidine as a novel scaffold for biofilm modulation

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06871K, PaperErick A. Lindsey, Roberta J. Worthington, Cristina Alcaraz, Christian MelanderAn efficient synthetic route to a series of substituted 2-aminopyrimidine (2-AP) derivatives has been developed. Several derivatives displayed the ability to modulate bacterial biofilm formation, exhibiting greater activity against Gram-positive strains than Gram-negative strains.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Conformationally restricted dynamic supramolecular catalysts for substrate-selective epoxidations

RSC - Organic Biomolecular Chemistry — Fri, 03 Feb 2012 21:36:08 +0100

Org. Biomol. Chem., 2012, Advance ArticleDOI: 10.1039/C2OB06859A, PaperEsmaeil Sheibani, Kenneth WarnmarkA second generation of supramolecular catalysts has been developed displaying increased substrate selectivity in epoxidations of styrene and stilbene derivatives.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Wide-range protein photo-crosslinking achieved by a genetically encoded N[varepsilon]-(benzyloxycarbonyl)lysine derivative with a diazirinyl moiety

RSC - Mol. BioSyst. latest articles — Fri, 03 Feb 2012 21:36:08 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05321G, CommunicationTatsuo Yanagisawa, Nobumasa Hino, Fumie Iraha, Takahito Mukai, Kensaku Sakamoto, Shigeyuki YokoyamaA method for wide-range in vivo protein photo-crosslinking has been developed by the site-specific incorporation of a large, photo-crosslinkable, non-natural amino acid into proteins.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers

RSC - Mol. BioSyst. latest articles — Fri, 03 Feb 2012 21:36:08 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05424H, PaperGoncalo Graca, Brian J. Goodfellow, Antonio S. Barros, Silvia Diaz, Iola F. Duarte, Konstantina Spagou, Kirill Veselkov, Elizabeth J. Want, John C. Lindon, Isabel M. Carreira, Eulalia Galhano, Cristina Pita, Ana M. GilA UPLC-MS study of 2nd trimester maternal urine and amniotic fluid to investigate metabolic effects of pregnancy disorders.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Dense surface functionalization using peptides that recognize differences in organized structures of self-assembling nanomaterials

RSC - Mol. BioSyst. latest articles — Fri, 03 Feb 2012 21:36:08 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05435C, PaperToshiki Sawada, Hisakazu MiharaCell adhesion to the fine-structured peptide nanofiber was highly up-regulated by modification with the plural RGDS conjugated nanofiber specific peptides.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Analysis of cell adhesion during early stages of colon cancer based on an extended multi-valued logic approach

RSC - Mol. BioSyst. latest articles — Fri, 03 Feb 2012 21:36:08 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05277F, PaperDaniel V. Guebel, Ulf Schmitz, Olaf Wolkenhauer, Julio VeraHere we present the first large scale multi-valued logic model investigating the signalling pathways that regulate cell adhesion during colorectal cancer initiation.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Forced homodimerization of the c-Fos leucine zipper in designed bHLHZ-like hybrid proteins MaxbHLH-Fos and ArntbHLH-Fos

RSC - Mol. BioSyst. latest articles — Fri, 03 Feb 2012 21:36:08 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05354C, PaperGang Chen, Antonia T. De Jong, Jumi A. ShinThe c-Fos leucine zipper does not homodimerize in its native bZIP. However, when fused to the bHLH motif to form a non-native hybrid, this zipper dimerizes, leading to DNA-binding function.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Development of diacyltetrol lipids as activators for the C1 domain of protein kinase C

RSC - Mol. BioSyst. latest articles — Fri, 03 Feb 2012 21:36:08 +0100

Mol. BioSyst., 2012, Advance ArticleDOI: 10.1039/C2MB05452C, PaperNarsimha Mamidi, Sukhamoy Gorai, Rakesh Mukherjee, Debasis MannaExperimental and computational studies were carried out to provide insights into the PKC C1b domain binding by the novel diacyltetrol lipids.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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A single amino acid residue can determine the sensitivity of SERCAs to artemisinins

Nature Structural and Molecular Biology — Fri, 03 Feb 2012 21:28:24 +0100

Nature Structural & Molecular Biology 19, 264 (2012). doi:10.1038/nsmb0212-264 Author: Anne-Catrin Uhlemann, Angus Cameron, Ursula Eckstein-Ludwig, Jorge Fischbarg, Pavel Iserovich, Felipe A Zuniga, Malcolm East, Anthony Lee, Leo Brady, Richard K Haynes & Sanjeev Krishna (Source: Nature Structural and Molecular Biology)

The E3 ubiquitin ligase TRIM11 mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expanded PHOX2B

Journal of Molecular Medicine — Fri, 03 Feb 2012 17:52:37 +0100

Abstract Expansions of a polyalanine (polyA) stretch in the coding region of the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by the absence of adequate control of autonomic breathing. Expansion of polyA in PHOX2B leads to protein misfolding and accumulation into inclusions. The mechanisms that regulate mutant protein degradation and turnover have been poorly elucidated. Here, we investigate the regulation of degradation of wild-type and polyA-expanded PHOX2B. We show that expanded PHOX2B is targeted for degradation through the ubiquitin–proteasome system, resulting in lowered levels of the mutant protein relative to its wild-type counterpart. Moreover, we show that mutant PHOX2B forms ubiquitin-positive inclusions...

microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis

Journal of Molecular Medicine — Fri, 03 Feb 2012 17:52:36 +0100

Abstract Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T ...

Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus

Journal of Molecular Medicine — Fri, 03 Feb 2012 17:52:35 +0100

Abstract Increasing evidences suggest that the type I interferon α (IFNα) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFNα1bScFv01 and corresponding whole antibody AIFNα1bIgG01 to human interferon α1b (IFNα1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFNα1b or naïve IFNα from SLE patients’ sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFNα1bScFv0...

The Role of Shox2 in SAN Development and Function

Pediatric Cardiology — Fri, 03 Feb 2012 17:51:33 +0100

Abstract Embryonic development is a tightly regulated process, and many families of genes functions to provide a regulatory genetic network to achieve such a program. The homeobox genes are an extensive family that encodes transcription factors with a characteristic 60-amino acid homeodomain. Mutations in these genes or in the encoded proteins might result in structural malformations, physiological defects, and even embryonic death. Mutations in the short-stature homeobox gene (SHOX) is associated with idiopathic short stature in humans, as observed in patients with Turner syndrome and/or Leri-Weill dyschondrosteosis. A closely related human homolog, SHOX2, has not been linked to any syndrome or defect so far. In mice, a SHOX ortholog gene is not present in the genome; howev...

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[News & Analysis] Cell Biology: Donation Spurs a Cell Observatory—And Bigger Plans

Science: Current Issue — Fri, 03 Feb 2012 17:34:11 +0100

The Broad Institute received a $32.5 million gift last week to take on one of the biggest challenges in biology: mapping the molecular "circuitry" inside several kinds of mammalian cells.Author: Jocelyn Kaiser (Source: Science: Current Issue)

C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo

Apoptosis — Fri, 03 Feb 2012 17:12:22 +0100

This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl4-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl4-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced sign...

GRAS proteins: the versatile roles of intrinsically disordered proteins in plant signalling.

The Biochemical Journal — Fri, 03 Feb 2012 16:48:46 +0100

Authors: Sun X, Jones WT, Rikkerink EH Abstract IDPs (intrinsically disordered proteins) are highly abundant in eukaryotic proteomes and important for cellular functions, especially in cell signalling and transcriptional regulation. An IDR (intrinsically disordered region) within an IDP often undergoes disorder-to-order transitions upon binding to various partners, allowing an IDP to recognize and bind different partners at various binding interfaces. Plant-specific GRAS proteins play critical and diverse roles in plant development and signalling, and act as integrators of signals from multiple plant growth regulatory and environmental inputs. Possessing an intrinsically disordered N-terminal domain, the GRAS proteins constitute the first functionally required unfoldome from the pl...

Device Provides A Platform For Viewing Cancer Cells And Other Macromolecules In Dynamic, Life-Sustaining Liquid Environments

Health News from Medical News Today — Fri, 03 Feb 2012 09:00:00 +0100

A photograph of a polar bear in captivity, no matter how sharp the resolution, can never reveal as much about behavior as footage of that polar bear in its natural habitat. The behavior of cells and molecules can prove even more elusive. Limitations in biomedical imaging technologies have hampered attempts to understand cellular and molecular behavior, with biologists trying to envision dynamic processes through static snapshots... (Source: Health News from Medical News Today)

Incongruity of Imaging Using Fluorescent 2-DG Conjugates Compared to 18F-FDG in Preclinical Cancer Models

Molecular Imaging and Biology — Fri, 03 Feb 2012 07:21:22 +0100

Conclusions These results suggest that conjugation of large bulky fluorophores to 2-DG disrupts the facilitated transport and retention of these probes in cells. Therefore, optical imaging of NIR 2-DG probes cannot substitute for 18F-FDG positron emission tomography imaging as a biomarker of tumor cell viability and metabolism. Content Type Journal ArticleCategory Brief ArticlePages 1-8DOI 10.1007/s11307-012-0545-3Authors Jen-Chieh Tseng, Lurie Family Imaging Center, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USAYuchuan Wang, Lurie Family Imaging Center, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USAPallab Banerjee, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02...

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New international standards to aid data sharing

MEDEV News — Fri, 03 Feb 2012 06:38:29 +0100

Led by researchers at University of Oxford (UK) and the Harvard Stem Cell Institute (HSCI) at Harvard University, (USA), more than 50 collaborators at over 30 scientific organizations around the globe have agreed on a common standard for integrating biological data sets. This will make it possible to consistently describe the enormous and radically different databases that are compiled in the biosciences in fields ranging from genetics to stem cell science, to environmental studies.This collaborative effort provides a way for scientists in widely disparate life science fields to co-ordinate each other's findings by allowing behind-the-scenes combination of the mountains of data produced by modern, technology driven science. This will allow researchers to put data to work more effectively a...

Biomarkers of Oxidative Stress and Cancer. From Chemistry, Biology to Clinical Applications and Personalized Therapy.

Current Molecular Medicine — Fri, 03 Feb 2012 05:00:00 +0100

Authors: Georgakilas AG, Panayiotidis M PMID: 22303842 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine)

QSAR Applications During Last Decade on Inhibitors of Acetylcholinesterase in Alzheimer's Disease.

Mini Reviews in Medicinal Chemistry — Fri, 03 Feb 2012 05:00:00 +0100

This article reviews multi-criteria QSAR applications on Acetylcholinesterase inhibitors as palliative drugs for Alzheimer's Disease, published in the period 2001-2011. It includes QSAR models for different series of compounds, comparative studies, and advances in methodologies. This period is marked by a shift in focus from palliative treatment to pathogenesis. However, we believe that research into palliative treatment should continue. More comparative studies are desirable. In order to facilitate comparative and general studies on Acetylcholinesterase inhibitors, a standard experimental protocol for measuring an inhibitor's potency is needed. Finally, we recommend chemists to work closely with system and molecular biologists. PMID: 22303974 [PubMed - as supplied by publisher] (Sourc...

Evidence for a genetic role in varicose veins and chronic venous insufficiency.

Phlebology — Fri, 03 Feb 2012 05:00:00 +0100

Authors: Krysa J, Jones GT, van Rij AM Abstract There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous d...