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Author (up) de Jong, A.; Dondorp, W.J.; Frints, S.G.M.; de Die-Smulders, C.E.M.; de Wert, G.M.W.R. file  url
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  Title Advances in prenatal screening: the ethical dimension Type Journal Article
  Year 2011 Publication Nature Reviews. Genetics Abbreviated Journal Nat Rev Genet  
  Volume 12 Issue 9 Pages 657-663  
  Keywords Abortion, Eugenic; Aneuploidy; Child; *Chromosome Aberrations; Ethics, Medical; Female; Genetic Association Studies/*methods; Genetic Testing; Humans; Infant, Newborn; Karyotyping; Neonatal Screening/*ethics; Patient Rights/ethics; Pregnancy; Prenatal Diagnosis/ethics/methods; Sequence Analysis, DNA  
  Abstract Prenatal screening strategies are undergoing rapid changes owing to the introduction of new testing techniques. The overall tendency is towards broadening the scope of prenatal testing through increasingly sensitive ultrasound scans and genome-wide molecular tests. In addition, non-invasive prenatal diagnosis is likely to be introduced in the near future. These developments raise important ethical questions concerning meaningful reproductive choice, the autonomy rights of future children, equity of access and the proportionality of testing.  
  Call Number Serial 1356  
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Author (up) Kepert, I.; Fonseca, J.; Muller, C.; Milger, K.; Hochwind, K.; Kostric, M.; Fedoseeva, M.; Ohnmacht, C.; Dehmel, S.; Nathan, P.; Bartel, S.; Eickelberg, O.; Schloter, M.; Hartmann, A.; Schmitt-Kopplin, P.; Krauss-Etschmann, S. file  url
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  Title D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease Type Journal Article
  Year 2017 Publication The Journal of Allergy and Clinical Immunology Abbreviated Journal J Allergy Clin Immunol  
  Volume 139 Issue 5 Pages 1525-1535  
  Keywords D-tryptophan; allergic airway disease; bacterial substance; gut microbiota; immune modulation; probiotic bacteria; screening  
  Abstract BACKGROUND: Chronic immune diseases, such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals, such as probiotics, for the prevention of allergic disease. However, clinical trials have produced inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host's microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty. OBJECTIVE: We sought to identify and characterize a bioactive probiotic metabolite for potential prevention of allergic airway disease. METHODS: Probiotic supernatants were screened for their ability to concordantly decrease the constitutive CCL17 secretion of a human Hodgkin lymphoma cell line and prevent upregulation of costimulatory molecules of LPS-stimulated human dendritic cells. RESULTS: Supernatants from 13 of 37 tested probiotic strains showed immunoactivity. Bioassay-guided chromatographic fractionation of 2 supernatants according to polarity, followed by total ion chromatography and mass spectrometry, yielded C11H12N2O2 as the molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-tryptophan. In contrast, L-tryptophan and 11 other D-amino acids were inactive. Feeding D-tryptophan to mice before experimental asthma induction increased numbers of lung and gut regulatory T cells, decreased lung TH2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced gut microbial diversity, which was increased by D-tryptophan. CONCLUSIONS: D-tryptophan is a newly identified product from probiotic bacteria. Our findings support the concept that defined bacterial products can be exploited in novel preventative strategies for chronic immune diseases.  
  Call Number Serial 1934  
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Author (up) Schenone, M.; Dancik, V.; Wagner, B.K.; Clemons, P.A. file  url
openurl 
  Title Target identification and mechanism of action in chemical biology and drug discovery Type Journal Article
  Year 2013 Publication Nature Chemical Biology Abbreviated Journal Nat Chem Biol  
  Volume 9 Issue 4 Pages 232-240  
  Keywords Animals; Biomarkers, Pharmacological/chemistry/*metabolism; *Drug Discovery; *Drug Evaluation, Preclinical; *High-Throughput Screening Assays; Humans; Isotope Labeling; Mass Spectrometry; Molecular Targeted Therapy; Phenotype; RNA Interference; Reverse Genetics; Saccharomyces cerevisiae/drug effects/genetics/metabolism; Small Molecule Libraries/chemistry/*metabolism/pharmacology; Validation Studies as Topic  
  Abstract Target-identification and mechanism-of-action studies have important roles in small-molecule probe and drug discovery. Biological and technological advances have resulted in the increasing use of cell-based assays to discover new biologically active small molecules. Such studies allow small-molecule action to be tested in a more disease-relevant setting at the outset, but they require follow-up studies to determine the precise protein target or targets responsible for the observed phenotype. Target identification can be approached by direct biochemical methods, genetic interactions or computational inference. In many cases, however, combinations of approaches may be required to fully characterize on-target and off-target effects and to understand mechanisms of small-molecule action.  
  Call Number Serial 1592  
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Author (up) Sinha, R.P.; Häder, D.-P. file  url
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  Title UV-protectants in cyanobacteria Type Journal Article
  Year 2008 Publication Plant Science Abbreviated Journal Plant Science  
  Volume 174 Issue 3 Pages 278-289  
  Keywords Cyanobacteria; Mycosporine-like amino acids (MAAs); Scytonemin; UV-screening compounds; UV radiation  
  Abstract Cyanobacteria are the largest group of Gram-negative photosynthetic prokaryotes on earth and have a cosmopolitan distribution. As cyanobacteria are believed to have originated in the Precambrian era at a time when the ozone shield was absent, they presumably faced high fluxes of UV radiation, which must have acted as an evolutionary pressure leading to the selection for efficient UV radiation protecting mechanisms. Tolerance of cyanobacteria to intense sunlight as well as UV radiation might have contributed to their success during early stages of colonization. The synthesis of UV-absorbing/screening compounds is an important mechanism to prevent UV-induced photodamage. In cyanobacteria photoprotectants such as mycosporine-like amino acids (MAAs) and scytonemin strongly absorb in the UV-A and/or UV-B region of the spectrum, and thus play an important role in allowing these organisms to grow and survive in habitats exposed to strong irradiation.  
  Call Number Serial 986  
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