TY - JOUR A1 - Hofmann, Ch. A1 - Sandig, V. A1 - Jennings, G. A1 - Rudolph, Michael A1 - Schlag, Peter M. A1 - Strauss, M. T1 - Efficient gene transfer into human hepatocytes by baculovirus vectors Y1 - 1995 ER - TY - THES A1 - Noll, Michael G. T1 - Understanding and leveraging the social web for information retrieval Y1 - 2010 CY - Potsdam ER - TY - INPR A1 - Kaufmann, Liane A1 - Mazzocco, Michele M. A1 - Dowker, Ann A1 - von Aster, Michael G. A1 - Goebel, Silke M. A1 - Grabner, Roland H. A1 - Henik, Avishai A1 - Jordan, Nancy C. A1 - Karmiloff-Smith, Annette D. A1 - Kucian, Karin A1 - Rubinsten, Orly A1 - Szucs, Denes A1 - Shalev, Ruth A1 - Nuerk, Hans-Christoph T1 - Dyscalculia from a developmental and differential perspective T2 - Frontiers in psychology Y1 - 2013 U6 - https://doi.org/10.3389/fpsyg.2013.00516 SN - 1664-1078 VL - 4 IS - 2 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Reschke, Stefan A1 - Sigfridsson, Kajsa G. V. A1 - Kaufmann, Paul A1 - Leidel, Nils A1 - Horn, Sebastian A1 - Gast, Klaus A1 - Schulzke, Carola A1 - Haumann, Michael A1 - Leimkühler, Silke T1 - Identification of a bis-molybdopterin intermediate in molybdenum cofactor biosynthesis in escherichia coli JF - The journal of biological chemistry N2 - The molybdenum cofactor is an important cofactor, and its biosynthesis is essential for many organisms, including humans. Its basic form comprises a single molybdopterin (MPT) unit, which binds a molybdenum ion bearing three oxygen ligands via a dithiolene function, thus forming Mo-MPT. In bacteria, this form is modified to form the bis-MPT guanine dinucleotide cofactor with two MPT units coordinated at one molybdenum atom, which additionally contains GMPs bound to the terminal phosphate group of the MPTs (bis-MGD). The MobA protein catalyzes the nucleotide addition to MPT, but the mechanism of the biosynthesis of the bis-MGD cofactor has remained enigmatic. We have established an in vitro system for studying bis-MGD assembly using purified compounds. Quantification of the MPT/molybdenum and molybdenum/phosphorus ratios, time-dependent assays for MPT and MGD detection, and determination of the numbers and lengths of Mo-S and Mo-O bonds by X-ray absorption spectroscopy enabled identification of a novel bis-Mo-MPT intermediate on MobA prior to nucleotide attachment. The addition of Mg-GTP to MobA loaded with bis-Mo-MPT resulted in formation and release of the final bis-MGD product. This cofactor was fully functional and reconstituted the catalytic activity of apo-TMAO reductase (TorA). We propose a reaction sequence for bis-MGD formation, which involves 1) the formation of bis-Mo-MPT, 2) the addition of two GMP units to form bis-MGD on MobA, and 3) the release and transfer of the mature cofactor to the target protein TorA, in a reaction that is supported by the specific chaperone TorD, resulting in an active molybdoenzyme. Y1 - 2013 U6 - https://doi.org/10.1074/jbc.M113.497453 SN - 0021-9258 SN - 1083-351X VL - 288 IS - 41 SP - 29736 EP - 29745 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER - TY - JOUR A1 - Schorck, Torben A1 - Christlieb, Norbert A1 - Cohen, Judy G. A1 - Beers, Timothy C. A1 - Shectman, Steve A1 - Thompson, Ian A1 - McWilliam, Andrew A1 - Bessell, Michael S. A1 - Norris, John E. A1 - Meléndez, Jorge A1 - Ramïrez, Solange A1 - Haynes, D. A1 - Cass, Paul A1 - Hartley, Malcolm A1 - Russell, Ken A1 - Watson, Fred A1 - Zickgraf, Franz-Josef A1 - Behnke, Berit A1 - Fechner, Cora A1 - Fuhrmeister, Birgit A1 - Barklem, Paul S. A1 - Edvardsson, Bengt A1 - Frebel, Anna A1 - Wisotzki, Lutz A1 - Reimers, Dieter T1 - The stellar content of the Hamburg/ESO survey : V. the metallicity distribution function of the Galactic halo N2 - We determine the metallicity distribution function (MDF) of the Galactic halo by means of a sample of 1638 metal-poor stars selected from the Hamburg/ESO objective-prism survey (HES). The sample was corrected for minor biases introduced by the strategy for spectroscopic follow-up observations of the metal-poor candidates, namely "best and brightest stars first". Comparison of the metallicities [Fe/H] of the stars determined from moderate-resolution (i.e., R similar to 2000) follow-up spectra with results derived from abundance analyses based on high-resolution spectra (i.e., R > 20 000) shows that the [Fe/H] estimates used for the determination of the halo MDF are accurate to within 0.3 dex, once highly C-rich stars are eliminated. We determined the selection function of the HES, which must be taken into account for a proper comparison between the HES MDF with MDFs of other stellar populations or those predicted by models of Galactic chemical evolution. The latter show a reasonable agreement with the overall shape of the HES MDF for [Fe/H] > -3.6, but only a model of Salvadori et al. (2007) with a critical metallicity for low-mass star formation of Z(cr) = 10(-3.4) Z(circle dot) reproduces the sharp drop at [Fe/H] similar to -3.6 present in the HES MDF. Although currently about ten stars at [Fe/H] < -3.6 are known, the evidence for the existence of a tail of the halo MDF extending to [Fe/H] similar to -5.5 is weak from the sample considered in this paper, because it only includes two stars [Fe/H] < -3.6. Therefore, a comparison with theoretical models has to await larger statistically complete and unbiased samples. A comparison of the MDF of Galactic globular clusters and of dSph satellites to the Galaxy shows qualitative agreement with the halo MDF, derived from the HES, once the selection function of the latter is included. However, statistical tests show that the differences between these are still highly significant. Y1 - 2009 UR - http://www.aanda.org/ U6 - https://doi.org/10.1051/0004-6361/200810925 SN - 0004-6361 ER - TY - JOUR A1 - Reschke, Stefan A1 - Niks, Dimitri A1 - Wilson, Heather A1 - Sigfridsson, Kajsa G. V. A1 - Haumann, Michael A1 - Rajagopalan, K. V. A1 - Hine, Russ A1 - Leimkühler, Silke T1 - Effect of exchange of the cysteine molybdenum ligand with selenocysteine on the structure and function of the active site in human sulfite oxidase JF - Biochemistry N2 - Sulfite oxidase (SO) is an essential molybdoenzyme for humans, catalyzing the final step in the degradation of sulfur-containing amino acids and lipids, which is the oxidation of sulfite to sulfate. The catalytic site of SO consists of a molybdenum ion bound to the dithiolene sulfurs of one molybdopterin (MPT) molecule, carrying two oxygen ligands, and is further coordinated by the thiol sulfur of a conserved cysteine residue. We have exchanged four non-active site cysteines in the molybdenum cofactor (Moco) binding domain of human SO (SOMD) with serine using site-directed mutagenesis. This facilitated the specific replacement of the active site Cys207 with selenocysteine during protein expression in Escherichia coli. The sulfite oxidizing activity (k(cat)/K-M) of SeSOMD4Ser was increased at least 1.5-fold, and the pH optimum was shifted to a more acidic value compared to those of SOMD4Ser and SOMD4Cys(wt) X-ray absorption spectroscopy revealed a Mow Se bond length of 2.51 A, likely caused by the specific binding of Sec207 to the molybdenum, and otherwise rather similar square-pyramidal S/Se(Cys)(O2MoS2)-S-VI(MPT) site structures in the three constructs. The low-pH form of the Mo(V) electron paramagnetic resonance (EPR) signal of SeSOM4Ser was altered compared to those of SOMD4Ser and SOMD4cy,(,), with g, in particular shifted to a lower magnetic field, due to the Se ligation at the molybdenum. In contrast, the Mo(V) EPR signal of the high-pH form was unchanged. The substantially stronger effect of substituting selenocysteine for cysteine at low pH as compared to high pH is most likely due to the decreased covalency of the Mo Se bond. Y1 - 2013 U6 - https://doi.org/10.1021/bi4008512 SN - 0006-2960 VL - 52 IS - 46 SP - 8295 EP - 8303 PB - American Chemical Society CY - Washington ER - TY - INPR A1 - Kucian, Karin A1 - Plangger, Fabienne A1 - O'Gorman, Ruth A1 - von Aster, Michael G. T1 - Operational momentum effect in children with and without developmental dyscalculia T2 - Frontiers in psychology KW - developmental dyscalculia KW - operational momentum KW - children KW - learning disability KW - numerical cognition KW - mental number line KW - symbolic calculation KW - attention Y1 - 2013 U6 - https://doi.org/10.3389/fpsyg.2013.00847 SN - 1664-1078 VL - 4 IS - 45 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - De Frenne, Pieter A1 - Rodriguez-Sanchez, Francisco A1 - Coomes, David Anthony A1 - Bäten, Lander A1 - Versträten, Gorik A1 - Vellend, Mark A1 - Bernhardt-Römermann, Markus A1 - Brown, Carissa D. A1 - Brunet, Jörg A1 - Cornelis, Johnny A1 - Decocq, Guillaume M. A1 - Dierschke, Hartmut A1 - Eriksson, Ove A1 - Gilliam, Frank S. A1 - Hedl, Radim A1 - Heinken, Thilo A1 - Hermy, Martin A1 - Hommel, Patrick A1 - Jenkins, Michael A. A1 - Kelly, Daniel L. A1 - Kirby, Keith J. A1 - Mitchell, Fraser J. G. A1 - Naaf, Tobias A1 - Newman, Miles A1 - Peterken, George A1 - Petrik, Petr A1 - Schultz, Jan A1 - Sonnier, Gregory A1 - Van Calster, Hans A1 - Waller, Donald M. A1 - Walther, Gian-Reto A1 - White, Peter S. A1 - Woods, Kerry D. A1 - Wulf, Monika A1 - Graae, Bente Jessen A1 - Verheyen, Kris T1 - Microclimate moderates plant responses to macroclimate warming JF - Proceedings of the National Academy of Sciences of the United States of America N2 - Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., "thermophilization" of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that "climatic lags" may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass-e.g., for bioenergy-may open forest canopies and accelerate thermophilization of temperate forest biodiversity. KW - climate change KW - forest management KW - understory KW - climatic debt KW - range shifts Y1 - 2013 U6 - https://doi.org/10.1073/pnas.1311190110 SN - 0027-8424 VL - 110 IS - 46 SP - 18561 EP - 18565 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Käser, Tanja A1 - Baschera, Gian-Marco A1 - Kohn, Juliane A1 - Kucian, Karin A1 - Richtmann, Verena A1 - Grond, Ursina A1 - Gross, Markus A1 - von Aster, Michael G. T1 - Design and evaluation of the computer-based training program Calcularis for enhancing numerical cognition JF - Frontiers in psychology N2 - This article presents the design and a first pilot evaluation of the computer-based training program Calcularis for children with developmental dyscalculia (DD) or difficulties in learning mathematics. The program has been designed according to insights on the typical and atypical development of mathematical abilities. The learning process is supported through multimodal cues, which encode different properties of numbers. To offer optimal learning conditions, a user model completes the program and allows flexible adaptation to a child's individual learning and knowledge profile. Thirty-two children with difficulties in learning mathematics completed the 6-12-weeks computer training. The children played the game for 20 min per day for 5 days a week. The training effects were evaluated using neuropsychological tests. Generally, children benefited significantly from the training regarding number representation and arithmetic operations. Furthermore, children liked to play with the program and reported that the training improved their mathematical abilities. KW - learning KW - intervention KW - optimization KW - calculation KW - spatial representation KW - interactive learning environment Y1 - 2013 U6 - https://doi.org/10.3389/fpsyg.2013.00489 SN - 1664-1078 VL - 4 IS - 31 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Pfeifer, Marion A1 - Schatz, Bertrand A1 - Picó, F. Xavier A1 - Passalacqua, Nicodemo G. A1 - Fay, Michael F. A1 - Carey, Pete D. A1 - Jeltsch, Florian T1 - Phylogeography and genetic structure of the orchid "Himantoglossum hircinum" (L.) Spreng. across its European central-marginal gradient N2 - Aim This study aims to link demographic traits and post-glacial recolonization processes with genetic traits in Himantoglossum hircinum (L.) Spreng (Orchidaceae), and to test the implications of the central-marginal concept (CMC) in Europe. Location Twenty sites covering the entire European distribution range of this species. Methods We employed amplified fragment length polymorphism (AFLP) markers and performed a plastid microsatellite survey to assess genetic variation in 20 populations of H. hircinum located along central-marginal gradients. We measured demographic traits to assess population fitness along geographical gradients and to test for correlations between demographic traits and genetic diversity. We used genetic diversity indices and analyses of molecular variance (AMOVA) to test hypotheses of reduced genetic diversity and increased genetic differentiation and isolation from central to peripheral sites. We used Bayesian simulations to analyse genetic relationships among populations. Results Genetic diversity decreased significantly with increasing latitudinal and longitudinal distance from the distribution centre when excluding outlying populations. The AMOVA revealed significant genetic differentiation among populations (F-ST = 0.146) and an increase in genetic differentiation from the centre of the geographical range to the margins (except for the Atlantic group). Population fitness, expressed as the ratio N-R/N, decreased significantly with increasing latitudinal distance from the distribution centre. Flower production was lower in most eastern peripheral sites. The geographical distribution of microsatellite haplotypes suggests post-glacial range expansion along three major migratory pathways, as also supported by individual membership fractions in six ancestral genetic clusters (C1-C6). No correlations between genetic diversity (e.g. diversity indices, haplotype frequency) and population demographic traits were detected. Main conclusions Reduced genetic diversity and haplotype frequency in H. hircinum at marginal sites reflect historical range expansions. Spatial variation in demographic traits could not explain genetic diversity patterns. For those sites that did not fit into the CMC, the genetic pattern is probably masked by other factors directly affecting either demography or population genetic structure. These include post-glacial recolonization patterns and changes in habitat suitability due to climate change at the northern periphery. Our findings emphasize the importance of distinguishing historical effects from those caused by geographical variation in population demography of species when studying evolutionary and ecological processes at the range margins under global change. Y1 - 2009 UR - http://www3.interscience.wiley.com/journal/117963685/home U6 - https://doi.org/10.1111/j.1365-2699.2009.02168.x SN - 0305-0270 ER -