Detection of small-molecule enzyme inhibitors with peptides isolated from phage-displayed combinatorial peptide libraries

AbstractBackground: The rapidly expanding list of pharmacologically important targets has highlighted the need for ways to discover new inhibitors that are independent of functional assays. We have utilized peptides to detect inhibitors of protein function. We hypothesized that most peptide ligands identified by phage display would bind to regions of biological interaction in target proteins and that these peptides could be used as sensitive probes for detecting low molecular weight inhibitors that bind to these sites.Results: We selected a broad range of enzymes as targets for phage display and isolated a series of peptides that bound specifically to each target. Peptide ligands for each target contained similar amino acid sequences and competition analysis indicated that they bound one or two sites per target. Of 17 peptides tested, 13 were found to be specific inhibitors of enzyme function. Finally, we used two peptides specific for Haemophilus influenzae tyrosyl-tRNA synthetase to show that a simple binding assay can be used to detect small-molecule inhibitors with potencies in the micromolar to nanomolar range.Conclusions: Peptidic surrogate ligands identified using phage display are preferentially targeted to a limited number of sites that inhibit enzyme function. These peptides can be utilized in a binding assay as a rapid and sensitive method to detect small-molecule inhibitors of target protein function. The binding assay can be used with a variety of detection systems and is readily adaptable to automation, making this platform ideal for high-throughput screening of compound libraries for drug discovery

Ethnic and gender specific life expectancies of the Singapore population, 1965 to 2009 - Converging, or diverging?

10.1186/1471-2458-13-1012BMC Public Health131

Experimental measurement-device-independent quantum digital signatures

The development of quantum networks will be paramount towards practical and secure telecommunications. These networks will need to sign and distribute information between many parties with information-Theoretic security, requiring both quantum digital signatures (QDS) and quantum key distribution (QKD). Here, we introduce and experimentally realise a quantum network architecture, where the nodes are fully connected using a minimum amount of physical links. The central node of the network can act either as a totally untrusted relay, connecting the end users via the recently introduced measurement-device-independent (MDI)-QKD, or as a trusted recipient directly communicating with the end users via QKD. Using this network, we perform a proof-of-principle demonstration of QDS mediated by MDI-QKD. For that, we devised an efficient protocol to distil multiple signatures from the same block of data, thus reducing the statistical fluctuations in the sample and greatly enhancing the final QDS rate in the finite-size scenario

Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

10.1371/journal.pone.0057015PLoS ONE83

Quinoline Group Modified Carbon Nanotubes for the Detection of Zinc Ions

Carbon nanotubes (CNTs) were covalently modified by fluorescence ligand (glycine-N-8-quinolylamide) and formed a hybrid material which could be used as a selective probe for metal ions detection. The anchoring to the surface of the CNTs was carried out by the reaction between the precursor and the carboxyl groups available on the surface of the support. Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA) unambiguously proved the existence of covalent bonds between CNTs and functional ligands. Fluorescence characterization shows that the obtained organic–inorganic hybrid composite is highly selective and sensitive (0.2 μM) to Zn(II) detection

Functionalized Mesoporous SBA-15 with CeF3: Eu3+ Nanoparticle by Three Different Methods: Synthesis, Characterization, and Photoluminescence

Luminescence functionalization of the ordered mesoporous SBA-15 silica is realized by depositing a CeF3: Eu3+ phosphor layer on its surface (denoted as CeF3: Eu3+/SBA-15/IS, CeF3: Eu3+/SBA-15/SI and CeF3: Eu3+/SBA-15/SS) using three different methods, which are reaction in situ (I-S), solution impregnation (S-I) and solid phase grinding synthesis (S-S), respectively. The structure, morphology, porosity, and optical properties of the materials are well characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, N2 adsorption, and photoluminescence spectra. These materials all have high surface area, uniformity in the mesostructure and crystallinity. As expected, the pore volume, surface area, and pore size of SBA-15 decrease in sequence after deposition of the CeF3: Eu3+ nanophosphors. Furthermore, the efficient energy transfer in mesoporous material mainly occurs between the Ce3+ and the central Eu3+ ion. They show the characteristic emission of Ce3+ 5d → 4f (200–320 nm) and Eu3+5D0 → 7FJ(J = 1–4, with 5D0 → 7F1 orange emission at 588 nm as the strongest one) transitions, respectively. In addition, for comparison, the mesoporous material CeF3: Eu3+/SBA-15/SS exhibits the characteristic emission of Eu3+ ion under UV irradiation with higher luminescence intensity than the other materials

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Non-Adherence in Patients on Peritoneal Dialysis: A Systematic Review

Background: It has been increasingly recognized that non-adherence is an important factor that determines the outcome of peritoneal dialysis (PD) therapy. There is therefore a need to establish the levels of non-adherence to different aspects of the PD regimen (dialysis procedures, medications, and dietary/fluid restrictions). Methods: A systematic review of peer-reviewed literature was performed in PubMed, PsycINFO and CINAHL databases using PRISMA guidelines in May 2013. Publications on non-adherence in PD were selected by two reviewers independently according to predefined inclusion and exclusion criteria. Relevant data on patient characteristics, measures, rates and factors associated with non-adherence were extracted. The quality of studies was also evaluated independently by two reviewers according to a revised version of the Effective Public Health Practice Project assessment tool. Results: The search retrieved 204 studies, of which a total of 25 studies met inclusion criteria. Reported rates of nonadherence varied across studies: 2.6 1353% for dialysis exchanges, 3.9 1385% for medication, and 14.4 1367% for diet/fluid restrictions. Methodological differences in measurement and definition of non-adherence underlie the observed variation. Factors associated with non-adherence that showed a degree of consistency were mostly socio-demographical, such as age, employment status, ethnicity, sex, and time period on PD treatment. Conclusion: Non-adherence to different dimensions of the dialysis regimen appears to be prevalent in PD patients. There is a need for further, high-quality research to explore these factors in more detail, with the aim of informing intervention designs to facilitate adherence in this patient populatio

Genome-Wide Association Study Singles Out SCD and LEPR as the Two Main Loci Influencing Intramuscular Fat Content and Fatty Acid Composition in Duroc Pigs

[EN] Intramuscular fat (IMF) content and fatty acid composition affect the organoleptic quality and nutritional value of pork. A genome-wide association study was performed on 138 Duroc pigs genotyped with a 60k SNP chip to detect biologically relevant genomic variants influencing fat content and composition. Despite the limited sample size, the genome-wide association study was powerful enough to detect the association between fatty acid composition and a known haplotypic variant in SCD (SSC14) and to reveal an association of IMF and fatty acid composition in the LEPR region (SSC6). The association of LEPR was later validated with an independent set of 853 pigs using a candidate quantitative trait nucleotide. The SCD gene is responsible for the biosynthesis of oleic acid (C18:1) from stearic acid. This locus affected the stearic to oleic desaturation index (C18:1/C18:0), C18: 1, and saturated (SFA) and monounsaturated (MUFA) fatty acids content. These effects were consistently detected in gluteus medius, longissimus dorsi, and subcutaneous fat. The association of LEPR with fatty acid composition was detected only in muscle and was, at least in part, a consequence of its effect on IMF content, with increased IMF resulting in more SFA, less polyunsaturated fatty acids (PUFA), and greater SFA/PUFA ratio. Marker substitution effects estimated with a subset of 65 animals were used to predict the genomic estimated breeding values of 70 animals born 7 years later. Although predictions with the whole SNP chip information were in relatively high correlation with observed SFA, MUFA, and C18: 1/C18: 0 (0.48-0.60), IMF content and composition were in general better predicted by using only SNPs at the SCD and LEPR loci, in which case the correlation between predicted and observed values was in the range of 0.36 to 0.54 for all traits. 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