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  • 1
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    A new recombineering system for Photorhabdus and Xenorhabdus (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-02
    Description: Precise and fluent genetic manipulation is still limited to only a few prokaryotes. Ideally the highly advanced technologies available in Escherichia coli could be broadly applied. Our efforts to apply lambda Red technology, widely termed ‘recombineering’, in Photorhabdus and Xenorhabdus yielded only limited success. Consequently we explored the properties of an endogenous Photorhabdus luminescens lambda Red-like operon, Plu2934/Plu2935/Plu2936. Bioinformatic and functional tests indicate that Plu2936 is a 5’-3’ exonuclease equivalent to Redα and Plu2935 is a single strand annealing protein equivalent to Redβ. Plu2934 dramatically enhanced recombineering efficiency. Results from bioinformatic analysis and recombineering assays suggest that Plu2934 may be functionally equivalent to Red, which inhibits the major endogenous E. coli nuclease, RecBCD. The recombineering utility of Plu2934/Plu2935/Plu2936 was demonstrated by engineering Photorhabdus and Xenorhabdus genomes, including the activation of the 49-kb non-ribosomal peptide synthase (NRPS) gene cluster plu2670 by insertion of a tetracycline inducible promoter. After tetracycline induction, novel secondary metabolites were identified. Our work unlocks the potential for bioprospecting and functional genomics in the Photorhabdus, Xenorhabdus and related genomes.
    Keywords: Recombination
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Postglacial adjustment of steep, low-order drainage basins, Canadian Rocky Mountains (2013)
    Wiley
    Details
    Publication Date: 2013-11-21
    Description: [1]  It is generally argued that the legacy of Pleistocene glaciation results in increased sediment flux in mountain systems. An important, but not well-constrained, aspect of Pleistocene glacial erosion is the geomorphic decoupling of cirque basins from main river systems. This study provides a quantitative link between glacier-induced basin morphology, postglacial erosion and sediment delivery for mountain headwaters (with basin area 〈10 km 2 ). We analyze the morphology of 57 headwater basins in the Canadian Rockies, and establish postglacial sediment budgets for select basins. Notable differences in headwater morphology suggest different degrees of erosion by cirque glaciers, which we classify into headwater basins with either cirque or non-cirque morphology. Despite steeper slope gradients in cirque basins, higher mean postglacial erosion rates in basins with non-cirque morphology (0.43-0.6 mm a -1 ) compared to those in cirques (0.19-0.39 mm a -1 ) suggest a more complex relationship between hillslope erosion and slope gradient in calcareous mountain environments than implied by the threshold hillslope concept. Higher values of channel profile concavity and lower channel gradients in cirques imply lower transport capacities and, thus, lower sediment delivery ratios (SDR). These results are supported by i) postglacial SDR values for cirques of 〈15 % with SDRs for non-cirque basins of 〉28 %; and ii) larger fan sizes at outlets of non-cirque basins (~15 % of basin area) compared to cirques (~5 %). Although small headwater basins represent the steepest part of mountain environments and erode significant postglacial sediment, the majority of sediment remains in storage under interglacial climatic conditions and does not affect large-scale mountain river systems.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
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    An Order–Disorder Transition in the Conjugated Polymer MEH-PPV (2012)
    American Chemical Society (ACS)
    Details
    Publication Date: 2012-07-06
    Description: Journal of the American Chemical Society DOI: 10.1021/ja302408a
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 4
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    Time-resolved imaging of magnetoelectric switching in multiferroic MnWO_{4} (2011)
    American Physical Society (APS)
    Details
    Publication Date: 2011-11-08
    Description: Author(s): T. Hoffmann, P. Thielen, P. Becker, L. Bohatý, and M. Fiebig [Phys. Rev. B 84, 184404] Published Mon Nov 07, 2011
    Keywords: Magnetism
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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  • 5
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    Iodine containing species in the remote marine boundary layer: A link to oceanic phytoplankton (2011)
    Wiley
    Details
    Publication Date: 2011-10-18
    Description: Iodine containing species have been measured in the particle phase (PM2.5) and the gas phase during a ship campaign between January and February 2007 in the South Atlantic marine boundary layer (MBL). Methyl iodide (CH3I) in the gas phase and soluble iodine species, i.e. iodide, iodate and an unidentified organic iodine species (UOI), in PM2.5 were measured. Temporal variations of gaseous and particulate iodine species were investigated. The exposure of the sampled air masses to phytoplankton along the back-trajectories was studied using a lagrangian transport model and satellite observations of oceanic chlorophyll-a concentration. Significant correlations were found between the concentrations of iodine species and the average chlorophyll exposure along back-trajectories, indicating an emission from phytoplankton in the open ocean. Good correlations were found when the ship approached or crossed the active biological region in the West-southern Atlantic. These results strongly suggest a connection between iodine species and the phytoplankton in the ocean. This study was extended to examine the relation of the iodine measurements to satellite derived phytoplankton distributions. We show that specific phytoplankton species may have impact on different iodine containing species.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    Graphane sheets and crystals under pressure [Chemistry] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-04-27
    Description: Eight isomeric two-dimensional graphane sheets are found in a theoretical study. Four of these nets—two built on chair cyclohexanes, two on boat—are more stable thermodynamically than the isomeric benzene, or polyacetylene. Three-dimensional crystals are built up from the two-dimensional sheets, and their hypothetical behavior under pressure (up to 300 GPa) is explored. While the three-dimensional graphanes remain, as expected, insulating or semiconducting in this pressure range, there is a remarkable inversion in stability of the five crystals studied. Two stacking polytypes that are not the most stable at ambient pressure (one based on an unusual chair cyclohexane net, the other on a boat) are significantly stabilized with increasing pressure relative to stackings of simple chair sheets. The explanation may lie in the balance on intra and intersheet contacts in the extended arrays.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    HONO emissions from soil bacteria as a major source of atmospheric reactive nitrogen (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-09-14
    Description: Abiotic release of nitrous acid (HONO) in equilibrium with soil nitrite (NO2(-)) was suggested as an important contributor to the missing source of atmospheric HONO and hydroxyl radicals (OH). The role of total soil-derived HONO in the biogeochemical and atmospheric nitrogen cycles, however, has remained unknown. In laboratory experiments, we found that for nonacidic soils from arid and arable areas, reactive nitrogen emitted as HONO is comparable with emissions of nitric oxide (NO). We show that ammonia-oxidizing bacteria can directly release HONO in quantities larger than expected from the acid-base and Henry's law equilibria of the aqueous phase in soil. This component of the nitrogen cycle constitutes an additional loss term for fixed nitrogen in soils and a source for reactive nitrogen in the atmosphere.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oswald, R -- Behrendt, T -- Ermel, M -- Wu, D -- Su, H -- Cheng, Y -- Breuninger, C -- Moravek, A -- Mougin, E -- Delon, C -- Loubet, B -- Pommerening-Roser, A -- Sorgel, M -- Poschl, U -- Hoffmann, T -- Andreae, M O -- Meixner, F X -- Trebs, I -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1233-5. doi: 10.1126/science.1242266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biogeochemistry Department, Max Planck Institute for Chemistry, Mainz, Germany. robert.oswald@mpic.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24031015" target="_blank"〉PubMed〈/a〉
    Keywords: Ammonia/metabolism ; Atmosphere/chemistry ; Nitrogen/*metabolism ; *Nitrogen Fixation ; Nitrosomonas europaea/*metabolism ; Nitrous Acid/*metabolism ; Oxidation-Reduction ; Reactive Nitrogen Species/*metabolism ; *Soil Microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Immune versus natural selection: antibody aldolases with enzymic rates but broader scope (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-02-12
    Description: Structural and mechanistic studies show that when the selection criteria of the immune system are changed, catalytic antibodies that have the efficiency of natural enzymes evolve, but the catalytic antibodies are much more accepting of a wide range of substrates. The catalytic antibodies were prepared by reactive immunization, a process whereby the selection criteria of the immune system are changed from simple binding to chemical reactivity. This process yielded aldolase catalytic antibodies that approximated the rate acceleration of the natural enzyme used in glycolysis. Unlike the natural enzyme, however, the antibody aldolases catalyzed a variety of aldol reactions and decarboxylations. The crystal structure of one of these antibodies identified the reactive lysine residue that was selected in the immunization process. This lysine is deeply buried in a hydrophobic pocket at the base of the binding site, thereby accounting for its perturbed pKa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barbas, C F 3rd -- Heine, A -- Zhong, G -- Hoffmann, T -- Gramatikova, S -- Bjornestedt, R -- List, B -- Anderson, J -- Stura, E A -- Wilson, I A -- Lerner, R A -- CA27489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Dec 19;278(5346):2085-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9405338" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Catalytic/chemistry/immunology/*metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Decarboxylation ; *Evolution, Molecular ; Fructose-Bisphosphate Aldolase/chemistry/immunology/*metabolism ; Glycolysis ; Hydrogen-Ion Concentration ; Immunization ; Immunoglobulin Fab Fragments/chemistry/immunology/*metabolism ; Kinetics ; Lysine/chemistry/metabolism ; Mice ; Models, Molecular ; Protein Conformation ; Pyridoxal/metabolism ; Selection, Genetic ; Substrate Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Transcriptional plasticity promotes primary and acquired resistance to BET inhibition (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-09-15
    Description: Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukaemia (AML), bromodomain and extra terminal protein (BET) inhibitors are being explored as a promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced haematological malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukaemia, here we perform a chromatin-focused RNAi screen in a sensitive MLL-AF9;Nras(G12D)-driven AML mouse model, and investigate dynamic transcriptional profiles in sensitive and resistant mouse and human leukaemias. Our screen shows that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET inhibitor resistance in AML. PRC2 suppression does not directly affect the regulation of Brd4-dependent transcripts, but facilitates the remodelling of regulatory pathways that restore the transcription of key targets such as Myc. Similarly, while BET inhibition triggers acute MYC repression in human leukaemias regardless of their sensitivity, resistant leukaemias are uniformly characterized by their ability to rapidly restore MYC transcription. This process involves the activation and recruitment of WNT signalling components, which compensate for the loss of BRD4 and drive resistance in various cancer models. Dynamic chromatin immunoprecipitation sequencing and self-transcribing active regulatory region sequencing of enhancer profiles reveal that BET-resistant states are characterized by remodelled regulatory landscapes, involving the activation of a focal MYC enhancer that recruits WNT machinery in response to BET inhibition. Together, our results identify and validate WNT signalling as a driver and candidate biomarker of primary and acquired BET resistance in leukaemia, and implicate the rewiring of transcriptional programs as an important mechanism promoting resistance to BET inhibitors and, potentially, other chromatin-targeted therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rathert, Philipp -- Roth, Mareike -- Neumann, Tobias -- Muerdter, Felix -- Roe, Jae-Seok -- Muhar, Matthias -- Deswal, Sumit -- Cerny-Reiterer, Sabine -- Peter, Barbara -- Jude, Julian -- Hoffmann, Thomas -- Boryn, Lukasz M -- Axelsson, Elin -- Schweifer, Norbert -- Tontsch-Grunt, Ulrike -- Dow, Lukas E -- Gianni, Davide -- Pearson, Mark -- Valent, Peter -- Stark, Alexander -- Kraut, Norbert -- Vakoc, Christopher R -- Zuber, Johannes -- England -- Nature. 2015 Sep 24;525(7570):543-7. doi: 10.1038/nature14898. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. ; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria. ; Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, 1090 Vienna, Austria. ; Boehringer Ingelheim - Regional Center Vienna GmbH, 1121 Vienna, Austria. ; Department of Medicine, Hematology &Medical Oncology, Weill Cornell Medical College, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367798" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Azepines/*pharmacology ; Cell Line, Tumor ; Chromatin/genetics/metabolism ; Drug Resistance, Neoplasm/*drug effects/*genetics ; Enhancer Elements, Genetic/genetics ; Female ; Gene Expression Regulation, Neoplastic/*drug effects/genetics ; Genes, myc/genetics ; Leukemia, Myeloid, Acute/drug therapy/*genetics/metabolism/pathology ; Male ; Mice ; Nuclear Proteins/*antagonists & inhibitors/metabolism ; Transcription Factors/*antagonists & inhibitors/metabolism ; Transcription, Genetic/*drug effects/genetics ; Triazoles/*pharmacology ; Wnt Signaling Pathway/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 10
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    Cryovolcanism on Ceres (2016)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2016-09-02
    Description: Volcanic edifices are abundant on rocky bodies of the inner solar system. In the cold outer solar system, volcanism can occur on solid bodies with a water-ice shell, but derived cryovolcanic constructs have proved elusive. We report the discovery, using Dawn Framing Camera images, of a landform on dwarf planet Ceres that we argue represents a viscous cryovolcanic dome. Parent material of the cryomagma is a mixture of secondary minerals, including salts and water ice. Absolute model ages from impact craters reveal that extrusion of the dome has occurred recently. Ceres’ evolution must have been able to sustain recent interior activity and associated surface expressions. We propose salts with low eutectic temperatures and thermal conductivities as key drivers for Ceres’ long-term internal evolution.
    Keywords: Geochemistry, Geophysics, Planetary Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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