740 research outputs found
Jahrbuch des S.A.C / 21 Le versant suisse de la chaîne du Mont Blanc : vue prise de la Tête de Vari (2873 m.)
No full text[Wilhelm Bernhard Benteli] ; d'après une photogr. de L. Kurz, Neuchâtel ; [phototypie:] C. Angerer & GöschlHeutiger Name des Aufnahmestandortes: Mont de la Foul
Social determinants of health in different welfare state environments : a comparison of men and women in Austria and Sweden
No full textAuthor Evelyn Angerer, BAAbstract in englischer SpracheMasterarbeit Universität Linz 201
Detection of ROS and the chemical characterization of human thoracic aortic tissue by confocal raman microscopy
No full textAuthor Christian Angerer, BScMasterarbeit Universität Linz 2022Arbeit auf den öffentlichen PCs in den Bibliotheken der JKU+Medizin abrufba
Representational dynamics in the domain of iterated mental paper folding
No full textAngerer B, Schreiber C. Representational dynamics in the domain of iterated mental paper folding. Cognitive Systems Research. 2019;54:217-231
Multiple PositivecisElements Regulate the Asymmetric Expression of theSpHEGene along the Sea Urchin Embryo Animal–Vegetal Axis
No full textAbstractThe mechanism that establishes the maternally determined animal–vegetal axis of sea urchin embryos is unknown. We have analyzed thecis-regulatory elements of theSpHEgene ofStrongylocentrotus purpuratus,which is asymmetrically expressed along this axis, in an effort to identify components of maternal positional information. Previously, we defined a regulatory region that is sufficient to provide correct nonvegetal expression of a β-galactosidase reporter gene (Wei, Z., Angerer, L. M., Gagnon, M. L., and Angerer, R. C.,Dev. Biol.171, 195–211, 1995). We have now analyzed this region intensively in order to determine if the spatial pattern is controlled by nonvegetal-positive activities or by vegetal-negative activities. The regulatory sequences, except the basal promoter, were mutated by either deletion or sequence replacement. None of these mutations resulted in ectopic β-gal expression in vegetal cells, showing that no single negativeciselement is responsible for the lack of vegetalSpHEtranscription. Surprisingly, even short segments of the regulatory region containing only several identifiedciselements also direct nonvegetal expression. Furthermore, theSpHEbasal promoter functions effectively in vegetal cells in combination withcis-acting elements derived from the PMC-specific gene,SM50.We conclude that the spatial pattern ofSpHEtranscription is achieved by multiple positive activities concentrated in nonvegetal cells. The vegetal expression ofSM50also is regulated only by positive activities (Makabe, K. W., Kirchhamer, C. V., Britten, R. J., and Davidson, E. H.,Development121, 1957–1970, 1995). A chimeric promoter containing bothSpHEandSM50regulatory sequences is active ubiquitously, suggesting that these regulators are not reciprocally repressive. These observations suggest a model in which theSpHEandSM50genes are activated by separate sets of positive maternal activities concentrated, respectively, in nonvegetal and vegetal domains of the early embryo
Space radiation research in Europe: flight experiments and ground-based studies.
Full text linkExposure to space radiation has long been acknowledged as a potential showstopper for long-duration manned interplanetary missions. In an effort to gain more information on space radiation risk and to develop countermeasures, NASA initiated several years ago a Space Radiation Health Program, which is currently supporting biological experiments performed at the Brookhaven National Laboratory. Accelerator-based radiobiology research in the field of space radiation research is also under way in Russia and Japan. The European Space Agency (ESA) supports research in the field in three main directions: spaceflight experiments on the International Space Station; modeling and simulations of the space radiation environment and transport; and, recently, ground-based radiobiology experiments exploiting the high-energy SIS18 synchrotron at GSI in Germany (IBER program). Several experiments are currently under way within IBER, and so far, beams of C and Fe-ions at energies between 11 and 1,000 MeV/n have been used in cell and tissue targets
Peutingeriana tabula itineraria in Bibliotheca Palatina Vindobonensi [Material cartográfico]: asservata nunc primum arte photographica expressa
No full textTabula Peutingeriana es un itinerario que muestra la red de carreteras del Imperio romano. El mapa original fue realizado a partir del siglo IV, ya que aparece Constantinopla, que fue fundada en el año 328. Cubre Europa, partes de Asia (India) y África del Norte. El nombre del mapa proviene de Konrad Peutinger, un humanista alemán de los siglos XV y XVIRepresentación de poblaciones mediante edificios de diferentes tamaños. - Arbolado. - Hidrografía
Functional and structural studies on the Atmungsferment Cytochrome c oxidase from Paracoccus denitrificans
No full textCytochrome c oxidase (CcO), also called Complex IV of the aerobic respiratory chain, is located in the plasma membrane of prokaryotes and in the inner mitochondrial membrane of eukaryotes. The redox energy of dioxygen reduction is used to translocate protons across the membrane resulting in an electrochemical proton gradient. The generated proton gradient is exploited by the adenosine-5’-triphosphate synthase. In this work, bacterial four-subunit aa3-Type CcO from Paracoccus denitrificans (ATCC 13543, 4 SU-wt ATCC CcO) was used for analyses. 1) The recombinant homologously produced 4 SU-wt CcO (4 SU-wt rec CcO) was functionally compared with the native 4 SU-wt ATCC CcO. The 4 SU-wt rec CcO showed functional deficiencies as determined by UV-vis spectroscopy and electron paramagnetic resonance (EPR) studies. Total X-ray Reflection Fluorescence measurements show in both wild type CcOs the same ratio of the redoxactive Fe and Cu (2 Fe : 3 Cu) indicating full complement of the functional metals. If CcO contains only subunit I and II, it loses its functional integrity during continuous turnover activity. The importance of subunit III for integrity of CcO was demonstrated using 2 SU-wt rec CcO. Crystallisation trials of suicide inactivated 2 SU-wt rec CcOs have been ineffective using standard crystallisation conditions. Crystals of active 2 SU-wt rec CcO (positive control) have been obtained under these conditions and this result indicates possible structural changes in suicide inactivated 2 SU-wt rec CcO. The structure of active 2 SU-wt rec CcO was determined to 2.25 Å resolution. 2) Terminal oxidases require four electrons for the cleavage of the dioxygen bond (O=O). In general, the catalytic cycle of CcO is described by the electron input and thus by the different redox states of the metal centres: the O, E, R, P and F state. The two-electron reduced R intermediate is able to donate four electrons for dioxygen reduction forming the P state. The P intermediate is an oxoferryl state implying the lack of an electron for the R -> P transition, because the metal centres can only provide three electrons (Fe+II forms Fe+IV and Cu+II forms Cu+I). The P state, where the dioxygen bond is already broken, shows an oxoferryl state (FeIV=O2-) and a nearby tyrosine is proposed to form a tyrosyl radical representing the donor of the missing electron. H2O2-induced artificial intermediates provide the opportunity to investigated different catalytic intermediates in detail. Mixing equimolar amounts of H2O2 to CcO in the O state induces the "two-electron" reduced PH state at high pH and the electronically equal "two-electron" reduced F• H state at low pH. The addition of an excess amount of H2O2 leads to the three-electron reduced FH state. Functional studies using the 4 SU-wt ATCC CcO have demonstrated a bound peroxide (O- - O-) intermediate during the catalytic cycle. Using EPR it was previously shown that Y167 hosts a radical species in PH/F• H state which suggests that Y167 could provide this "missing electron". While X-ray structural models of CcO and Fourier-transformed infrared (FTIR) measurements of oxygenated ("pulsed") 4 SU-wt ATCC CcO suggest a bound peroxide in the O state, UV-vis and EPR spectroscopic studies indicate that other intermediates may also contain such peroxide species. Equimolar and excess amounts of H2O2 induce the PH/F• H and FH states, respectively and catalase treatment of the FH state leads, contrary to the natural direction of the catalytic cycle, to the apparent transition of the FH -> PH/F• H states, which is accompanied by reappearance of an EPR signal from the Y167• radical. The novel PFH/F• FH states are presented here and we postulate that the FH state hosts a superoxide (or peroxide) adduct at CuB in the binuclear site. In addition, the novel P10 state is also introduced having a maximum at lambda = 612 nm in the difference absorption spectrum (minus the O state). The P10 state is induced by mixing CcO in the O state with a pH 10 buffer. This pH 10 induced state resembles standard P states such as PCO, PH and PR. However, the P10 state evolves out of the O state without addition of reduction equivalents. Using EPR spectroscopy it was shown that Y167 hosts a radical species in the P10 state such as in the PH state. In summary, all functional data presented here provide evidence for a peroxide bound during the O state. Finally, a new model for the natural catalytic cycle is proposed. If the O state contains a peroxide, it is also likely that the E and R state contain this species. Even the oxoferryl intermediates P and F states may complex a peroxide at CuB in the binuclear site. 3) The amino acid residue Y167, which hosts the radical in the PH/F•H states, is not directly part of the binuclear site of CcO. For identification of the primary electron donor, two tryptophan variants of CcO, W272F and W164F, which are located nearby the binuclear site, were produced. Evidence is provided that W272 is a kinetically fast electron donor for the O2 molecule. The electron is replenished by Y167, or probably by Y280 in the natural cycle. The Y167 radical is detectable by EPR spectroscopy after treatment with equimolar amounts of H2O2 in the active variant W164F, but is absent in the inactive variant W272F. 4) CcO contains two proton conducting pathways, the D- and the K-pathway. Proteoliposomes of the variants H28A and D30N, mutations located at the entrance of the D-pathway, both show the identical proton pumping activity as the 4 SU-wt rec CcO (pumped H+/e- = 1). The variant N113D shows abolished proton pumping (pumped H+/e- = 0), but a relative high cytochrome c oxidation activity (63 %). G196D displays no cytochrome c oxidation and proton pumping activity. Overall, the addition or removal of a negative charge within the D-pathway such as in D124N, N131D, N113D and G196D leads to a decoupled phenotype indicating the high degree of electrostatic coupling in CcO.Die Cytochrom c Oxidase (CcO) ist ein integrales Membranprotein, das in fast allen aeroben Organismen vorhanden ist und bildet den Komplex IV der aeroben Atmungskette. Die Redoxenergie der Sauerstoffreduktion wird durch die membranständigen Komplexe der Atmungskette ausgenutzt, um Protonen über die Membran zu transportieren und somit einen elektrochemischen Protonengradienten aufzubauen. Die Komplexe der prokaryotischen Atmungskette befinden sich in der Plasmamembran und die Protonen werden vom Cytosol ins Periplasma gepumpt, während die eukaryotische Atmungskette in der inneren Membran der Mitochondrien lokalisiert ist, und die Protonen von der Matrix in den Intermembranraum gepumpt werden. Zusätzlich zu den aktiv gepumpten Protonen werden weitere Ladungen an beiden Seiten der Membran verschoben: die Elektronen von reduzierten Cytochrom cs werden von der Aussenseite der Membran zum Sauerstoff weitergeleitet und die Substratprotonen für die Wasserbildung gelangen von der Innenseite der Membran zum Sauerstoff, und diese Ladungsverschiebungen und -neutralisationen machen insgesamt 50 % des elektrochemischen Potentials aus. Die gespeicherte Energie des produzierten elektrochemischen Protonengradienten wird von der Adenosin-5´-triphosphat (ATP) Synthase zur Synthese von ATP genutzt. Die redox-aktive CcO hat vier Metallzentren, die an den Redoxreaktionen beteiligt sind: Das dinukleare CuA-Zentrum, welches Elektronen von reduziertem Cytochrom c empfängt, das Häm a und das binukleare Häm a3-CuB Zentrum. Im binuklearen Fea3-CuB Zentrum findet die Sauerstoffreduktion zu zwei Wassermolekülen statt, bei der pro Sauerstoffmolekül vier Elektronen und vier Substratprotonen benötigt werden. Der katalytische Zyklus der CcO wird in verschiedene Intermediate aufgeteilt, die die einzelnen Redoxstufen des Enzyms widerspiegeln: der oxidierte O Zustand wird durch eine ein-Elektron Reduktion in den E Zustand überführt. Ein weiterer Reduktionsschritt führt zum zwei-Elektronen reduzierten R Zustand, welcher nach der Bindung von Sauerstoff, über den A Zustand, durch Elektronenumlagerung zum P Zustand reagiert. Der P Zustand ist nach einem putativen Peroxy-Intermediat benannt, ist aber tatsächlich ein nachgewiesenes Oxoferryl-Intermediat. Zusätzlich wurde im P Zustand ein Tyrosylradikal mittels elektronenparamagnetischer Resonanz-(EPR-)Spektroskopie identifiziert. Der nächste Reduktionsschritt, die Reduktion des Tyrosylradikals zum Tyrosinrest, führt zum Oxoferryl-Intermediat F Zustand. Das vierte Elektron führt die CcO zurück in ihren Grundzustand, dem O Zustand. Einige dieser katalytischen Zustände lassen sich künstlich durch Zugabe von H2O2 induzieren, wobei je nach zugegebener H2O2-Menge unterschiedliche Intermediate hervorgebracht werden. Equimolare Mengen an H2O2 induzieren bei hohem pH den PH Zustand und bei niedrigem pH den protonierten F•H Zustand. Beide Intermediate haben gleich viele Elektronen, d.h. den gleichen Redoxzustand, jedoch unterscheiden sie sich in ihrem Protonierungsgrad. Ein Überschuss an zugegebenem H2O2 induziert den FH Zustand. H2O2- induzierte, künstliche Intermediate ermöglichen den katalytischen Zyklus der CcO im Modell zu studieren. In dieser Arbeit wurde die Typ aa3 CcO des Bodenbakteriums Paracoccus denitrificans (Stamm ATCC 13543) untersucht. P. denitrificans CcO besteht aus vier Untereinheiten gegenüber der Rinderherz-CcO, die aus 13 Untereinheiten zusammengesetzt ist. Die Kristallisation der funktionell aktiven zwei-Untereinheiten Form der P. denitrificans CcO zusammen mit einem Antikörperfragment (Fv Fragment) ermöglichte die Strukturbestimmung bei einer Auflösung von 2,7 Å (Ostermeier, C., Harrenga, A., Ermler, U., Michel, H. (1997) "Structure at 2.7 Å resolution of the Paracoccus denitrificans two-subunit cytochrome c oxidase complexed with an antibody Fv fragment." PNAS 94 (20): 10547-10553). 1) In dieser Arbeit wurde ein homologes Expressionssystem für die Produktion einer rekombinanten Wildtyp CcO genutzt. Das Gen der Untereinheit I (ctaDIIbeta) der CcO, das in dem P. denitrificans AO1-Deletionstamm über den Expressionsvektor pUP39 exprimiert wurde, ist ohne Affinitätsanhängsel kloniert worden. Die rekombinante Wildtyp CcO wurde auf gleiche Weise wie die native Wildtyp CcO mit Hilfe des Fv Fragments gereinigt. Die funktionellen Eigenschaften der rekombinant produzierten Wildtyp CcO wurden mit denen der nativen Wildtyp CcO verglichen. Es konnte gezeigt werden, dass rekombinant produzierte Wildtyp CcO gegenüber der nativen Wildtyp CcO a) weniger Aktivität b) Verschiebungen im Redox-Differenzabsorptionsspektrum c) niedrige Ausbeute an UV-vis spektroskopisch messbaren Intermediaten (PH, F•H und FH Zustände) und d) weniger Ausbeute an EPR spektroskopisch messbaren Tyrosylradikalen im PH/F•H Zustand aufwieß. Die beobachteten Unterschiede hätten durch das Fehlen von redox-aktiven Metallen in der rekombinanten Wildtyp CcO verursacht werden können. Die Überexpression des Gens der Untereinheit I der rekombinanten Wildtyp CcO könnte die Maschinerie der Proteinbiosynthese und die Rekrutierung von Kupfer- oder Hämgruppen-Einbauhilfsproteinen (Häm/Cu-Chaperone) überfordert haben. Die Untersuchung der Metallzusammensetzung der Wildtyp CcOs mittels Totalreflektions-Röntgenfluoreszenz-Analyse ergab für beide Proteine das korrekte Verhältnis der redox-aktiven Metalle von zwei Fe zu drei Cu. Für die Rinderherz-CcO konnte von einer anderen Gruppe dieses Forschungsfeldes gezeigt werden, dass sie aus dem Vorrat von Membranlipiden überwiegend Phosphatidylglycerin (PG) mit (18:1)-delta11-Vaccensäureresten selektiert, obwohl PG mit (18:1)-delta9-Ölsäureresten in der Membran viel häufiger vorkommt (Shinzawa-Itoh K. et al., (2007) Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase, EMBO, 26, 1713–1725). Der AO1-Deletionsstamm könnte durch sein verändertes Expressionsmuster eine andere Komposition von Lipiden in seiner Biomembran aufweisen, was die reduzierte Funktion der rekombinanten Wildtyp CcO erklären könnte, da sie nicht-funktionelle Lipide gebunden haben könnte. ...
Dibenzo[a,f]quinolizines: syntheses and cytostatic activity in estrogen-sensitive tumor cells
No full textA number of methoxy-substituted 7,11b,12,13-tetrahydro-6H-dibenzo-[a,f]quinolizines with short alkyl groups in position 6 or 12 were synthesized by the Bischler-Napieralski reaction using the appropriate starting material followed by a second ring closure reaction involving a base-generated benzyne intermediate. The methoxy functions in positions 2 or 3 and 9 were cleaved with BBr3 and the free hydroxy groups converted into the acetates. The enantiomers of two of these derivatives were separated by liquid chromatography on triacetylcellulose. Compounds with alkyl substituents bind strongly to the estrogen receptor except those with a cis-orientation at the central ring connection. The RBA values ranged from 2.2-10.8 (17 beta-estradiol: RBA = 100). There was no major difference in binding between the (+) and (-)-enantiomers. The 3,9-diacetoxy-6-alkyl derivatives also showed binding affinity for the progesterone receptor (RBA: 1.2-3.1). The 2,9-diacetoxydibenzoquinolizines trans-61 and -6m with ethyl and propyl respectively in position 12 strongly inhibited the growth of hormone-sensitive MCF-7 breast cancer cells at concentrations of 10(-6) M and higher but were inactive in hormone-independent MDA-MB 231 breast cancer cells. Preliminary tests with hormone-dependent MXT mouse mammary tumors as model showed that these compounds have also antineoplastic activity in vivo. Derivative trans-61 at a dose of 20 mg/kg body weight, administered 3 times/week, inhibited the growth of these tumors by 78% (tamoxifen: 76% inhibition). Studies on the estrogenic and antiestrogenic properties of these agents in mice revealed that they are mixed agonists/antagonists with strong antiestrogenic activity at low doses but significant estrogenic effects at higher doses
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