Drug target identification using side-effect similarity     

Campillos M  Kuhn M  Gavin AC  Jensen LJ  Bork P 《Science (New York, N.Y.)》2008,321(5886):263-266

Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs.  相似文献   

Genome-scale proteomics reveals Arabidopsis thaliana gene models and proteome dynamics     

Baerenfaller K  Grossmann J  Grobei MA  Hull R  Hirsch-Hoffmann M  Yalovsky S  Zimmermann P  Grossniklaus U  Gruissem W  Baginsky S 《Science (New York, N.Y.)》2008,320(5878):938-941

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Electronic structure control of single-walled carbon nanotube functionalization     

Strano MS  Dyke CA  Usrey ML  Barone PW  Allen MJ  Shan H  Kittrell C  Hauge RH  Tour JM  Smalley RE 《Science (New York, N.Y.)》2003,301(5639):1519-1522

Diazonium reagents functionalize single-walled carbon nanotubes suspended in aqueous solution with high selectivity and enable manipulation according to electronic structure. For example, metallic species are shown to react to the near exclusion of semiconducting nanotubes under controlled conditions. Selectivity is dictated by the availability of electrons near the Fermi level to stabilize a charge-transfer transition state preceding bond formation. The chemistry can be reversed by using a thermal treatment that restores the pristine electronic structure of the nanotube.  相似文献   

Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists     

Monica D. Figueiredo  Michel L. Vandenplas  David J. Hurley  James N. Moore 《Veterinary immunology and immunopathology》2009,127(1-2):125-134

Our understanding of the innate immune response in the horse has been limited by a lack of definitive data concerning cell signaling in response to microbial products. Toll-like receptors (TLRs) recognize conserved molecular motifs of microbes and elicit immune responses through their coupling with intracellular adaptor molecules, particularly MyD88 and TRIF. To provide a more definitive characterization of TLR signaling in the horse, the objectives of this study were to: (1) characterize the responses of equine monocytes to TLR ligands that signal through MyD88, TRIF or both in other species, and (2) determine the profiles of gene expression initiated utilizing these adaptor molecules. Monocytes were used to establish concentration response curves for Escherichia coli lipopolysaccharide (LPS; TLR4 ligand) and N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine x 3 HCl (Pam₃CSK₄; TLR2 ligand) based on expression of procoagulant activity (PCA) and production of tumor necrosis factor-alpha (TNF-α); effects of polyinosine–polycytidylic acid (Poly I:C; TLR3 ligand) were determined by quantifying expression of mRNA for interferon-beta (IFN-ß). Expression of genes associated with the MyD88- (TNF-α, IL-1ß, IL-6 and IL-10) and TRIF-dependent pathways (IFN-ß, IP-10, RANTES and TRAF1) were measured at intervals spanning 20 h. LPS and Pam₃CSK₄ induced significantly higher expression of TNF-α, IL-1ß, and IL-10 than did Poly I:C. Poly I:C induced significantly higher expression of IFN-ß, IP-10 and RANTES than did either the TLR2 or TLR4 ligands. High concentrations of E. coli LPS did not significantly increase expression of genes associated with the TRIF-dependent pathway. The results of this study suggest that equine monocytes utilize a common intracellular pathway in response to TLR2 and TLR4 ligands, but a distinct pathway in response to TLR3 ligands.  相似文献   

Molar absorptivities and reducing capacity of pyranoanthocyanins and other anthocyanins     

Jordheim M  Aaby K  Fossen T  Skrede G  Andersen ØM 《Journal of agricultural and food chemistry》2007,55(26):10591-10598

To improve accuracy in the determination of anthocyanin purity and succeeding antioxidant capacity, 1H and 13C nuclear magnetic resonance spectroscopy have been combined with high-performance liquid chromatography (HPLC) equipped with a diode array detector and UV-vis spectroscopy in the analysis of anthocyanidin 3-glycosides and 5-carboxypyranoanthocyanidin 3-glycosides. The molar absoptivity (epsilon) values were found to be relatively similar, in contrast to previously reported literature values, and the average epsilon values for both anthocyanidin 3-monoglycosides and 5-carboxypyranoanthocyanidin 3-glycosides were proposed to be 22,000 and 23,000 in acidified aqueous and methanolic solutions, respectively. To assess the influence of structure on the potential antioxidant capacity of anthocyanins, the 3-glucosides of pelargonidin (1), cyanidin (2), peonidin (3), delphinidin (4), petunidin (5), malvidin (6), 5-carboxypyranopelargonidin (8), 5-carboxypyranocyanidin (9), 5-carboxypyranodelphinidin (11), 5-carboxypyranopetunidin (12), and 5-carboxypyranomalvidin (13) and the 3-galactosides of cyanidin (7) and 5-carboxypyranocyanidin (14) were examined by a ferric ion reducing antioxidant power (FRAP) assay. The reducing capacities of the individual anthocyanins were in the range of 0.9-5.2 micromol of Trolox equivalents/micromol. The two 5-carboxypyranoanthocyanins 11 and 9 and the four common anthocyanins 2, 4, 7, and 14, all possessing pyrogallol or catechol type of B rings, showed the highest antioxidant capacity measured by FRAP. However, the inclusion of the 5-hydroxyl in the D ring and just one oxygen substituent on the B ring in 8 diminished the reducing capacity considerably. Correspondingly, electrochemical behavior of 5-carboxypyranoanthocyanidin 3-glucosides and anthocyanidin 3-glucosides was derived using HPLC coupled to a coulometric array detector set from 100 to 800 mV in increments of 100 mV. The relative order of the reducing capacity of the various 5-carboxypyranoanthocyanidin 3-glucosides and anthocyanidin 3-glucosides were nearly alike, whether determined by coulometric array detection or FRAP.  相似文献   

Detection of the intranuclear microsporidian Enterospora nucleophila in gilthead sea bream by in situ hybridization     

Nahla Hossameldin Ahmed  Monica Caffara  Ariadna Sitj‐Bobadilla  Maria Letizia Fioravanti  Angelica Mazzone  Abbass Sayed Aboulezz  Asmaa Mohamed Metwally  Mosaab Adl‐Eldin Omar  Oswaldo R. Palenzuela 《Journal of fish diseases》2019,42(6):809-815

Enterospora nucleophila is an intranuclear microsporidian responsible for emaciative microsporidiosis of gilthead sea bream (GSB). Its minute size and cryptic nature make it easily misdiagnosed. An in situ hybridization (ISH) technique based on antisense oligonucleotide probes specific for the parasite was developed and used in clinically infected GSB in combination with calcofluor white stain (CW) and other histopathological techniques. The ISH method was found to label very conspicuously the cells containing parasite stages, with the signal concentrating in merogonial and sporogonial plasmodia within the infected cell nuclei. Comparison with CW demonstrated limited ISH signal in cells containing mature spores, which was attributed mostly to the scarcity of probe targets present in these stages. Although spores were detected in other organs of the digestive system as well as in the peripheral blood, proliferative stages or parasite reservoirs were not found in this work outside the intestines. The study demonstrated a frequent disassociation between the presence of abundant spores and the intensity of the infections as determined by the parasite activity. The ISH allows confirmatory diagnosis of GSB microsporidiosis and estimation of infection intensity and will be a valuable tool for a more precise determination of parasite dissemination pathways and pathogeny mechanisms.  相似文献   

Antagonistic activity of bacterial isolates from intestinal microbiota of Atlantic cod, Gadus morhua, and an investigation of their immunomodulatory capabilities     

Christopher Marlowe A Caipang  Monica F Brinchmann  & Viswanath Kiron 《Aquaculture Research》2010,41(2):249-256

In an effort to identify potential probionts, four bacterial strains obtained from the intestinal tract of wild-caught Atlantic cod, Gadus morhua , were tested for their antagonistic activity against Vibrio anguillarum and Aeromonas salmonicida , two of the most common bacterial pathogens in cod aquaculture, using a well-diffusion agar assay at two incubation temperatures: 13 and 20 °C. The tested bacteria exhibited dissimilarity in their inhibitory action against the target pathogens – an enhanced activity was particularly observed for strains GP11 and GS11 at the highest incubation temperature. Based on the 16S ribosomal DNA gene sequence analysis, the strains showed high similarity to Psychrobacter sp. (strain GP11), Shewanella sp. (GS11), Photobacterium sp. (GP31) and Vibrio sp. (GV11). The incubation of Atlantic cod head kidney cells with the heat-inactivated probiotic strains resulted in the differential expression of immune-response genes that are related to bacterial defence and inflammation. Thus, the gut-derived bacterial strains have probiotic potential and their possible immunomodulatory capabilities could be determined under in vitro conditions.  相似文献   

Simultaneous detection of pathogens causing francisellosis,furunculosis and vibriosis in Atlantic cod by multiplex polymerase chain reaction     

Amod Kulkarni  Christopher Marlowe A Caipang  Monica F Brinchmann  Viswanath Kiron 《Aquaculture Research》2010,41(10):1533-1538

An assay for the simultaneous detection of three major bacterial pathogens of Atlantic cod with multiplex polymerase chain reaction (mPCR) was developed. Primers targeting the flanking regions of genes groEL, gyrB and amiB were standardized to diagnose francisellosis, furunculosis and vibriosis respectively. The detection limit of Francisella piscicida, Aeromonas salmonicida and Vibrio anguillarum in the mPCR assay ranged from 10 ng to 100 pg of bacterial DNA mL^?1, 10 μg to 50 ng of bacterial DNA mL^?1 and 1 μg to 100 ng of bacterial DNA mL^?1 respectively. These primers were found to be specific in the determination of the respective genes in the individual pathogen without cross‐reaction, thus making the assay an efficient tool to detect the presence of these pathogens simultaneously or individually.  相似文献   

What's in an index? Comparing the ecological information provided by two indices to assess the status of coralligenous reefs in the NW Mediterranean Sea          下载免费PDF全文

Luigi Piazzi  Carlo Nike Bianchi  Enrico Cecchi  Giulia Gatti  Ivan Guala  Carla Morri  Stéphane Sartoretto  Fabrizio Serena  Monica Montefalcone 《水产资源保护:海洋与淡水生态系统》2017,27(6):1091-1100

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Effects of supplementation of decapod zoea to Artemia basal diet on fatty acid composition and digestive gland histology in common octopus (Octopus vulgaris) paralarvae          下载免费PDF全文

Javier Roo  Juan Estefanell  Mónica B Betancor  Marisol Izquierdo  Hipólito Fernández‐Palacios  Juan Socorro 《Aquaculture Research》2017,48(2):633-645

The present study aimed to evaluate the effect of the supplementation of different crab zoeas to enriched Artemia basal diet for Octopus vulgaris paralarvae during the first month of life. Paralarvae were fed using enriched Artemia nauplii alone and Artemia co‐fed either first zoea stages of Grapsus adscensionis or Plagusia depressa. The experiment was carried out over a period of 28 days, in 0.12 m³ tanks with a flow‐through rearing system. Growth in dry weight as well as mantle length and width were assessed weekly. Additionally, prey and paralarvae fatty acid composition and digestive gland (DG) histology were evaluated. Addition of low amounts of crab zoeas (approx. 100 indv. L^?1 day^?1) provided during critical life stages of O. vulgaris proved to be good enough to improve paralarvae growth and survival in comparison with those fed exclusively on enriched Artemia. These results were supported by the finding of a higher number of glycoprotein absorption vacuoles in the DG from paralarvae co‐fed crab zoeas, suggesting a higher feeding activity. In addition, fatty acid analysis of crab zoea showed that these are good sources of dietary arachidonic and eicosapentaenoic acids during the octopus planktonic life stage, whereas the low docosahexaenoic (DHA) content suggests the use of additional DHA sources or higher zoea densities to meet paralarvae nutritional demand to carry out a successful metamorphosis to benthic life.  相似文献