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Code:
TOD
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Time Slot/Poster Number:
4:00-4:25
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Session:
Screening & "omics"
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19F NMR Screening of LEF, a library of chemical fragments with different Local Environment of Fluorine
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| Claudio Dalvit
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Italian Institute of Technology D3, Genova, Italy
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| Abstract |
The procedure and the criteria used in the design, selection and construction of a new fluorinated fragment library is presented. The library, named LEF (Local Environment of Fluorine), in combination with the 19F NMR transverse relaxation rate experiments, represents one of the most sensitive approaches for fragment screening and for probing the presence of fluorophilic protein environments. Proper set-up of this methodology, according to rules derived from presented theoretical simulations, allows the identification of very weak-affinity ligands and the simultaneous detection of multiple ligands contained within the same tested mixture. These NMR-hits are then used in the FAXS experiments for the fragment optimization process, for the follow-up screening and for binding constant measurements.
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Code:
TOD
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Time Slot/Poster Number:
4:25-4:40
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Session:
Screening & "omics"
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Metabolic flux analysis of cancer progression by NMR spectroscopy
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| Fabian V Filipp; David Scott; Adam Richardson; Christine Knutzen; Gary Chiang; Ze'ev Ronai; Andrei Osterman; Jeffrey Smith
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Burnham Institute for Medical Research, La Jolla, CA
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| Abstract |
Cancer is known to be associated with substantial rewiring of metabolic networks. When tumors outgrow blood supply, cancer cells have the ability to adapt to low oxygen. This hypoxic state requires a unique metabolic program for continued survival and proliferation. However, beyond a general shift from respiration to glycolysis, the details of this permissive metabolic program are unknown. Here, we introduce an integrated approach to assess pathway activities and concentrations of a large number of key components in cancer metabolism, metastasis and under hypoxia. We have developed a NMR processing pipeline that allows for simultaneous assessment of pool sizes and pathway activities. Metabolic flux analysis by NMR reveals key enzymes to be targeted in metabolite based cancer diagnostics and therapeutics.
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Code:
TOD
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Time Slot/Poster Number:
4:40-5:05
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Session:
Screening & "omics"
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One- and two- dimensional NMR techniques for the discovery of markers of floral origin and of bioactive compounds in honey.
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| Giangiacomo Beretta; Enrico Caneva; Roberto MaffeiFacino
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University of Milan, Milan, Italy
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| Abstract |
In this presentation will be discussed the technical aspects and the successful applications of a methodology based on one-dimensional nuclear magnetic resonance (NMR) and/or two-dimensional NMR analyses (COSY, HMQC, HMBC and DOSY NMR) of the chromatographic fractions obtained by reverse phase solid-phase extraction (SPE) of honeys from different botanical origins. Using this methodology, we have been able to identify different markers of botanical origin, among which kynurenic acid (KA), a tryptophan metabolite that acts as antagonist at the alpha-7 nicotinic receptor and at the glycine binding site of the NMDA receptor, and its 3-(2'-pyrrolidinyl) derivative) (3-PKA), the first member of a new class of alkaloid compounds.
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Code:
TOD
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Time Slot/Poster Number:
5:05-5:20
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Session:
Screening & "omics"
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Dynamic metabolic responses of mice to Schistosoma japonicum infection
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| Junfang Wu; Huiru Tang; Yulan Wang
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Wuhan Institute of Physics and Mathematics, CAS, Wuhan, China
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| Abstract |
Schistosomiasis has been reported affect 200 million people in more than 76 countries. As the main prevalent species in Asia region, millions of dollars have been spent in schistosoma japonicum (S. japonicum) infectious disease control in the past. Understanding the dynamic responses of the host metabolism to infection is essential to facilitate early diagnosis and prevent complications associated with schistosomiasis. Here, we investigate the dynamic metabolic consequences of S. japonicum infection in a mouse model, using NMR-based metabolic profiling technique combined with multivariate data analysis. Plasma and urine samples were obtained weekly from mice experimentally infected with 80 S japonicum cercariae until 5 weeks postinfection (p.i.). Liver samples were collected at sacrifice (5 weeks p.i.). The alterations of metabolites induced by the infection could be detected as early as 3 weeks p.i. onwards. In addition, the infection severity could be distinguished at 5 weeks p.i. The predominant metabolic alterations in S. japonicum infected mice consisted of stimulated glycolysis, depressed tricarboxylic acid cycle, disturbed lipid metabolism and gut microbiota. Moreover, the alterations of pyrimidine catabolism were also observed as indicated by the elevated urinary 3-ureidopropionate level, which appeared to be unique and has the potential to become a biomaker for early diagnosis. Our results provided insight into the dynamic variations during the development of schistosomiasis, and demonstrated the potential of metabonomics as a tool for early detection of S. japonicum infection.
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Code:
TOD
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Time Slot/Poster Number:
5:20-5:45
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Session:
Screening & "omics"
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Developing High Field NMR and Zero Field Dielectric and Diamagnetic Screening Instrumentation for Full Bottle Rare Wine Screening
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| Matt Augustine
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Univ of California, Davis, Davis, CA
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| Abstract |
Three methods of non-invasive, full bottle wine analysis are described. All three methods track wine solute concentration and use principal component analysis to reduce the dimensionality of the measured data while recovering maximum data variance. The full bottle high field 1H NMR spectroscopy and zero field dielectric and diamagnetic screening approaches involve some aspect of customized NMR instrumentation. The NMR approach uses specially designed magnetic field shims and probeheads while the dielectric and diamagnetic screening methods apply heterodyne detection common to high field NMR detection. The application of each of these approaches to full bottle rare wine libraries, an exhaustive study of the effects of transport and storage on diamagnetic screening data, and the identification of counterfeit wine are discussed.
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