| 1. |
- Aeluri, Madhu, et al.
(author)
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An Intramolecular Heck Approach To Obtain 17-Membered Macrocyclic Diversity and the Identification of an Antiangiogenesis Agent from a Zebrafish Assay
- 2013
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In: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :19, s. 3955-3958
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Journal article (peer-reviewed)abstract
- We report a practical and modular approach to obtain two different types of 17-membered ring macrocyclic compounds through an intramolecular Heck reaction. These macrocyclic compounds are functionalized, that is, they contain two contiguous stereogenic hydroxy functional groups and an amino acid moiety in the macrocyclic ring skeleton. The macrocycles were then screened against a zebrafish assay to determine the antiangiogenesis activity of these small molecules. Macrocyclic compound 2.2a was identified as a potent inhibitor at 2.5 M, whereas its acyclic precursor and the other related macrocyclic compounds did not show any effect.
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| 2. |
- Granhall, Ulf, et al.
(author)
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Bacterial community diversity in paper mills processing recycled paper
- 2010
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In: Journal of Industrial Microbiology & Biotechnology. - : Oxford University Press (OUP). - 1367-5435 .- 1476-5535. ; 37:10, s. 1061-1069
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Journal article (peer-reviewed)abstract
- Paper mills processing recycled paper suffer from biofouling causing roblems both in the mill and final product. The total bacterial ommunity composition and identification of specific taxa in the process ater and biofilms at the stock preparation and paper machine areas in a ill with recycled paper pulp was described by using a DNA-based pproach. Process water in a similar mill was also analyzed to nvestigate if general trends can be found between mills and over time. acterial community profiles, analyzed by terminal-restriction fragment ength polymorphism (T-RFLP), in process water showed that the dominant eaks in the profiles were similar between the two mills, although the verall composition was unique for each mill. When comparing process ater and biofilm at different locations within one of the mills, we bserved a separation according to location and sample type, with the iofilm from the paper machine being most different. 16S rRNA gene clone ibraries were generated and 404 clones were screened by RFLP analysis. rouping of RFLP patterns confirmed that the biofilm from the paper achine was most different. A total of 99 clones representing all RFLP atterns were analyzed, resulting in sequences recovered from nine acterial phyla, including two candidate phyla. Bacteroidetes epresented 45% and Actinobacteria 23% of all the clones. Sequences with imilarity to organisms implicated in biofouling, like Chryseobacterium pp. and Brevundimonas spp., were recovered from all samples even though he mill had no process problems during sampling, suggesting that they re part of the natural paper mill community. Moreover, many sequences howed little homology to as yet uncultivated bacteria implying that aper mills are interesting for isolation of new organisms, as well as or bioprospecting.
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| 3. |
- Guduru, Shiva Krishna Reddy, et al.
(author)
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Tetrahydroquinoline-Derived Macrocyclic Toolbox : The Discovery of Antiangiogenesis Agents in Zebrafish Assay
- 2013
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In: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 4:7, s. 666-670
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Journal article (peer-reviewed)abstract
- A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e. tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 mu M.
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| 4. |
- Jogula, Srinivas, et al.
(author)
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Building a Macrocyclic Toolbox from C-Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay
- 2013
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In: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2013:23, s. 5036-5040
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Journal article (peer-reviewed)abstract
- We report the synthesis of four different types of macrocyclic-derived glycohybrids from carbohydrates that have an amino acid moiety in the large-ring skeleton. These macrocyclic glycohybrids were obtained from -C-1H- and -C-1H-linked carbohydrates. In one series, we utilized ring-closing metathesis as the stitching technology to obtain two different macrocycles, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial-axial orientation) between C-1H and C-5H showed activity and their other diastereomers (i.e., equatorial-axial C-1H and C-5 H) with a trans relationship did not show any effect.
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| 5. |
- Nugent, Rebecca L., et al.
(author)
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Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation
- 2010
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11
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Journal article (peer-reviewed)abstract
- Background: Histone acetyltransferase enzymes (HATs) are implicated in egulation of transcription. HATs from different families may overlap in arget and substrate specificity. esults: We isolated the elp3(+) gene encoding the histone cetyltransferase subunit of the Elongator complex in fission yeast and haracterized the phenotype of an Delta elp3 mutant. We examined genetic nteractions between Delta elp3 and two other HAT mutants, Delta mst2 nd Delta gcn5 and used whole genome microarray analysis to analyze heir effects on gene expression. onclusions: Comparison of phenotypes and expression profiles in single, ouble and triple mutants indicate that these HAT enzymes have verlapping functions. Consistent with this, overlapping specificity in istone H3 acetylation is observed. However, there is no evidence for verlap with another HAT enzyme, encoded by the essential mst1(+) gene.
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| 6. |
- Petersson, Ulrika A., et al.
(author)
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The Prx Q protein of Arabidopsis thaliana is a member of the luminal chloroplast proteome
- 2006
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In: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 580:26, s. 6055-6061
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Journal article (peer-reviewed)abstract
- Peroxiredoxins have been discovered in many organisms ranging from eubacteria to mammals, and their known biological functions include both oxidant defense and signal transduction. The genome of Arabidopsis thaliana encodes for ten individual peroxiredoxins, of which four are located in the chloroplast. The best-characterized member of the chloroplast peroxiredoxins is 2-Cys Prx that is associated with the stroma side of the thylakoid membrane and is considered to participate in antioxidant defense and protection of photosynthesis. This study addressed the chloroplast peroxiredoxin Prx Q and showed that its subcellular location is the lumen of the thylakoid membrane. To get insight in the biological function of the Prx Q protein of Arabidopsis, the protein levels of the Prx Q protein in thylakoid membranes were studied under different light conditions and oxidative stress. A T-DNA knockout mutant of Prx Q did not show any visible phenotype and had normal photosynthetic performance with a slightly increased oxygen evolving activity.
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| 7. |
- Weinryb, Noomi, et al.
(author)
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Stepping Into and Out of the Void : Funding Dynamics of Human Embryonic Stem Cell Research in California, Sweden, and South Korea
- 2016
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In: Stem Cell Reviews. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:1, s. 8-14
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Journal article (peer-reviewed)abstract
- Nonprofit organizations and philanthropists stepped into a funding void caused by controversies over public funding of human embryonic stem cell (hESC) research. Based on interviews of 83 representatives of 53 funders, we examine the motivations and accountability structures of public agencies, corporations, fundraising dependent nonprofit organizations and philanthropic organizations that funded hESC research in three jurisdictions: California, Sweden, and South Korea. While non-traditional forms of funding are essential in the early stages of research advancement, they are unreliable for the long timeframes necessary to advance cell therapies. Such funding sources may enter the field based on high expectations, but may exit just as rapidly based on disappointing rates of progress.
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| 8. |
- Xue-Franzen, Yongtao, et al.
(author)
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Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles
- 2010
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11
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Journal article (peer-reviewed)abstract
- Background: Gcn5 is a transcriptional coactivator with histone cetyltransferase activity that is conserved with regard to structure as ell as its histone substrates throughout the eukaryotes. Gene egulatory networks within cells are thought to be evolutionarily iverged. The use of evolutionarily divergent yeast species, such as S. erevisiae and S. pombe, which can be studied under similar nvironmental conditions, provides an opportunity to examine the nterface between conserved regulatory components and their cellular pplications in different organisms. esults: We show that Gcn5 is important for a common set of stress esponses in evolutionarily diverged yeast species and that the activity f the conserved histone acetyltransferase domain is required. We define group of KCl stress response genes in S. cerevisiae that are pecifically dependent on Gcn5. Gcn5 is localised to many Gcn5-dependent enes including Gcn5 repressed targets such as FLO8. Gcn5 regulates ivergent sets of KCl responsive genes in S. cerevisiae and S. pombe. enome-wide localization studies showed a tendency for redistribution of cn5 during KCl stress adaptation in S. cerevisiae from short genes to he transcribed regions of long genes. An analogous redistribution was ot observed in S. pombe. onclusions: Gcn5 is required for the regulation of divergent sets of Cl stress-response genes in S. cerevisiae and S. pombe even though it s required a common group of stress responses, including the response o KCl. Genes that are physically associated with Gcn5 require its ctivity for their repression or activation during stress adaptation, roviding support for a role of Gcn5 as a corepressor as well as a oactivator. The tendency of Gcn5 to re-localise to the transcribed egions of long genes during KCl stress adaptation suggests that Gcn5 lays a specific role in the expression of long genes under adaptive onditions, perhaps by regulating transcriptional elongation as has been een for Gcn5 in S. pombe. Interestingly an analogous redistribution of cn5 is not seen in S. pombe. The study thus provides important new nsights in relation to why coregulators like Gcn5 are required for the orrect expression of some genes but not others.
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| 9. |
- Bergander, L, et al.
(author)
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Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole by liquid chromatography-mass spectrometry and NMR.
- 2003
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In: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 31:2, s. 233-241
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Journal article (peer-reviewed)abstract
- The tryptophan photoproduct 6-formylindolo[3,2-b] carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by H-1-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b] carbazole-6-carboxaldehyde (6-formylindolo[ 3,2-b] carbazole).
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| 10. |
- Svenaeus, Fredrik
(author)
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Phenomenology listens to Prozac : analyzing the SSRI revolution
- 2007
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In: Medical technologies and the life world. - Abingdon, Oxon, UK : Routledge. - 9780415364331 ; , s. 164-183
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Book chapter (other academic/artistic)abstract
- Focuses on the ways new health technologies intervene into our lives. This book explores: how new health technologies are understood by lay people and patients; how the outcomes of these technologies are communicated in various clinical settings; and, how these technologies can alter our notions of health and illness and create 'new illness'.
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