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Spatio-temporal control of cellular uptake achieved by photoswitchable cell-penetrating peptides
(2016)
The selective uptake of compounds into specific cells of interest is a major objective in cell biology and drug delivery. By incorporation of a novel, thermostable azobenzene moiety we generated peptides that can be switched optically between an inactive state and an active, cell-penetrating state with excellent spatio-temporal control.
Spatio-temporal control of cellular uptake achieved by photoswitchable cell-penetrating peptides
(2015)
The selective uptake of compounds into specific cells of interest is a major objective in cell biology and drug delivery. By incorporation of a novel, thermostable azobenzene moiety we generated peptides that can be switched optically between an inactive state and an active, cell-penetrating state with excellent spatio-temporal control.
The genetic integrity of each organism depends on the faithful segregation of its genome during mitosis. To meet this challenge, a cellular surveillance mechanism, termed the spindle assembly checkpoint (SAC), evolved that monitors the correct attachment of chromosomes and blocks progression through mitosis if corrections are needed. While the central role of the SAC for genome integrity is well established, its functional dissection has been hampered by the limited availability of appropriate small molecule inhibitors. Using a fluorescence polarization-based screen, we identify Mad2 inhibitor-1 (M2I-1), the first small molecule inhibitor targeting the binding of Mad2 to Cdc20, an essential protein-protein interaction (PPI) within the SAC. Based on computational and biochemical analyses, we propose that M2I-1 disturbs conformational dynamics of Mad2 critical for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens the SAC response, indicating that the compound might be active in cells. Thus, our study identifies the SAC specific complex formation between Mad2 and Cdc20 as a protein-protein interaction that can be targeted by small molecules.
Spatio-temporal control of cellular uptake achieved by photoswitchable cell-penetrating peptides
(2015)
The selective uptake of compounds into specific cells of interest is a major objective in cell biology and drug delivery. By incorporation of a novel, thermostable azobenzene moiety we generated peptides that can be switched optically between an inactive state and an active, cell-penetrating state with excellent spatio-temporal control.
SHRIMP U-Pb ages have been obtained for zircon in granitic gneisses from the aureole of the Rogaland anorthosite-norite intrusive complex, both from the ultrahigh temperature (UHT; >900 °C pigeonite-in) zone and from outside the hypersthene-in isograd. Magmatic and metamorphic segments of composite zircon were characterised on the basis of electron backscattered electron and cathodoluminescence images plus trace element analysis. A sample from outside the UHT zone has magmatic cores with an age of 1034 ± 7 Ma (2{sigma}, n = 8) and 1052 ± 5 Ma (1{sigma}, n = 1) overgrown by M1 metamorphic rims giving ages between 1020 ± 7 and 1007 ± 5 Ma.In contrast, samples from the UHT zone exhibit four major age groups:(1) magmatic cores yielding ages over 1500 Ma(2) magmatic cores giving ages of 1034 ± 13 Ma (2{sigma}, n = 4) and 1056 ± 10 Ma (1{sigma}, n = 1)(3) metamorphic overgrowths ranging in age between 1017 ± 6 Ma and 992 ± 7 Ma (1{sigma}) corresponding to the regional M1 Sveconorwegian granulite facies metamorphism, and(4) overgrowths corresponding to M2 UHT contact metamorphism giving values of 922 ± 14 Ma (2{sigma}, n = 6). Recrystallized areas in zircon from both areas define a further age group at 974 ± 13 Ma (2{sigma}, n = 4).This study presents the first evidence from Rogaland for new growth of zircon resulting from UHT contact metamorphism. More importantly, it shows the survival of magmatic and regional metamorphic zircon relics in rocks that experienced a thermal overprint of c. 950 °C for at least 1 Myr. Magmatic and different metamorphic zones in the same zircon are sharply bounded and preserve original crystallization age information, a result inconsistent with some experimental data on Pb diffusion in zircon which predict measurable Pb diffusion under such conditions. The implication is that resetting of zircon ages by diffusion during M2 was negligible in these dry granulite facies rocks. Imaging and Th/U-Y systematics indicate that the main processes affecting zircon were dissolution-reprecipitation in a closed system and solid-state recrystallization during and soon after M1.
The age of Proterozoic granulite facies metamorphism and deformation in the Strangways Metamorphic Complex (SMC) of central Australia is determined on zircon grown in syn-metamorphic and syn-deformational orthopyroxene-bearing, enderbitic, veins. SHRIMP zircon studies suggest that M1-M2 and the correlated periods of intense deformation (D1-D2) are part of a single tectonothermal event between 1,717-2 and 1,732-7 Ma. It is considered unlikely that the two metamorphic phases (M1, M2) suggested by earlier work represent separate events occurring within 10-25 Ma of each other. Previous higher estimates for the age of M1 granulite metamorphism in the SMC (Early Strangways event at ca. 1,770 Ma) based on U-Pb zircon dating of granitic, intrusive rocks, are not believed to relate to the metamorphism, but to represent pre-metamorphic intrusion ages. Conventional multi-grain U-Pb monazite analyses on high-grade metasediments from three widely spaced localities in the western SMC yield 207Pb/235U ages between 1,728-11 and 1,712-2 Ma. The age range of the monazites corresponds to the SHRIMP zircon ages in the granulitic veins and is interpreted to record monazite growth (prograde in the metasedimentary rocks). The data imply a maximum time-span of 30 Ma for high-grade metamorphism and deformation in the SMC. There is, thus, no evidence for an extremely long period of continuous high- temperature conditions from 1,770 to ca. 1,720 Ma as previously proposed. The results firmly establish that the SMC has a very different high-grade metamorphic history than the neighbouring Harts Range, where upper amphibolite facies metamorphism in the Palaeozoic caused widespread growth or recrystallization of monazite.
Nd whole-rock data from the Windmill Islands area yield early Proterozoic to middle Archaean Nd model ages. These crustal residence times are consistent with regional correlations with other parts of Antarctica (Bunger Hills, Denman Glacier area) and the Albany-Fraser Orogen of south-western Australia during the Mid-Proterozoic and thus support reconstructions with a continuous Mid-Proterozoic orogen in these areas. The new Nd isotope data provide strong evidence that no age boundary exists between the higher- and lower-grade parts of the Windmill Islands area, and that the metamorphic complex represents a single terrane with a common crustal history. The data support the notion of a time- link between the occurrence of intrusive charnockites (C-type magmas) and high-grade metamorphism. The magmatic rocks and orthogneisses in the area are interpreted to have a mixed source consisting of older crustal components, i.e. older sediments (ca. 3.2-2.6 Ga) and a younger mafic component (ca. 1.9 Ga). Two garnet Sm-Nd isochrons yield ages of 1156±17 Ma and 1137±2.5 Ma and are identical to SHRIMP U-Pb results on monazite from these samples. A garnet Sm-Nd age of 1123±13 Ma for the Ford granite is significantly younger than the SHRIMP U-Pb zircon age for this sample. The difference relates to the different closure temperature of each isotopic system and is thus interpreted as initial cooling after granulite facies metamorphism. Keywords. East Antarctica - Granulites - Garnet-whole rock isochrons - Intrusive charnockite - Nd model ages
Was wird unter „nachhaltiger Prävention“ in der Präventionsforschung verstanden? Welche guten Beispiele für nachhaltige Prävention gibt es in der Praxis? Und v. a.: Wie lässt sich Prävention in den verschiedenen Bereichen wie Kriminalität, Gewalt und Rechtsextremismus nachhaltig gestalten? Diesen Fragen will der vorliegende Sammelband nachgehen und damit der Präventionsdebatte neue Impulse verleihen. Der Band will insbesondere die nationale sowie internationale Fachdebatte konstruktiv aufgreifen, Theorie und Praxis verbinden, „good practice“ Beispiele darstellen sowie Perspektiven nachhaltiger Prävention aufzeigen. Mit diesem Themenspektrum richtet er sich sowohl an die Wissenschaft als auch an die Praxis sowie insgesamt an eine interessierte Öffentlichkeit.
The complex formation of the following diazaperylene ligands (L) 1,12-diazaperylene 1, 1,1-bisisoquinoline 2, 2,11-disubstituted 1,12-diazaperylenes (alkyl=methyl, ethyl, isopropyl, 3, 5, 7), 3,3-disubstituted 1,1-bisisoquinoline (alkyl=methyl, ethyl, isopropyl, 4, 6, 8 and with R=phenyl, 11 and with pyridine 12), and the 5,8-dimethoxy-substituted diazaperylene 9, 6,6-dimethoxy-substituted bisisoquinoline 10 with AgBF4 was investigated. Collision-induced dissociation measurements were used to evaluate the relative stabilities of the ligands themselves and for the [1:1](+) complexes as well as for the homoleptic and heteroleptic silver [1:2](+) complexes in the gas phase. This method is very useful in rapid screening of the stabilities of new complexes in the gas phase. The influence of the spatial arrangement of the ligands and the type of substituents employed for the complexation were examined. The effect of the preorganization of the diazaperylene on the threshold activation voltages and thus of the relative binding energies of the different complexes are discussed. Density functional theory calculations were used to calculate the optimized structures of the silver complexes and compared with the stabilities of the complexes in the gas phase for the first time.
Effects of the impact of natural long-term irradiation with alpha particles in one chamosite and one cordierite sample were characterised in detail using electron microprobe, Raman microprobe, optical absorption spectroscopy (cordierite only), and transmission electron microscopy (TEM; cordierite only) analysis. In both cases, the impact of He- 4 cores (alpha particles) that were emitted from actinide-bearing mineral inclusions has caused the formation of radiation damage haloes in the host mineral. These haloes have maximum radii of about 33 mu m (chamosite) and 47 mu m (cordierite). They show notably changed optical properties, i.e., intensified absorption of light as recognised by brown (chamosite) and yellow (cordierite) pleochroism and enhanced or even anomalous interference colours. In spite of the significant disturbance of their short range order, alpha particle haloes are characterised by generally low degrees of structural radiation damage. This is indicated by rather moderate broadening of vibrational bands and, in the case of cordierite, apparently undisturbed electron diffraction patterns in the TEM. Intensive damage, virtually close to an amorphous state, was only found in cordierite up to a few tens of nanometres away from actinide-bearing inclusions. This damage is mainly assigned to recoils of heavy nuclei upon emission of an alpha particle, which have particle trajectory lengths that are three orders of magnitude shorter than those of the alpha particles. Similar to observations on biotite, alpha particle haloes in chamosite and cordierite as observed in the optical microscope may be considered as representative of a very early stage of the metamictisation process
Der zweite Band der DIGAREC Series beinhaltet Beiträge der DIGAREC Lectures 2008/09 sowie des Wissenschaftsforums der Deutschen Gamestage 2008 und 2009. Mit Beiträgen von Oliver Castendyk (Erich Pommer Institut), Stephan Günzel mit Michael Liebe und Dieter Mersch (Universität Potsdam), Andreas Lange (Computerspielemuseum Berlin), Ingrid Möller mit Barbara Krahé (Universität Potsdam), Klaus Spieler (Institut für digitale interaktive Kultur Berlin), James Tobias (University of California, Riverside), Stefan Böhme (HBK Braunschweig), Robert Glashüttner (Wien), Sven Jöckel (Universität Erfurt) mit Leyla Dogruel (FU Berlin), Michael Mosel (Universität Marburg), Sebastian Quack (HTW Berlin), Leif Rumbke (Hamburg) und Steffen P. Walz (ETH Zürich).
In this work the adsorption of CO2 and CH4 on a series of isoreticular microporous metal-organic frameworks based on 2-substituted imidazolate-4-amide-5-imidates, IFP-1-IFP-6 (IFP Imidazolate Framework Potsdam), is studied firstly by pure gas adsorption at 273 K. All experimental isotherms can be nicely described by using the Toth isotherm model and show the preferred adsorption of CO2 over CH4. At low pressures the Toth isotherm equation exhibits a Henry region, wherefore Henry's law constants for CO2 and CH4 uptake could be determined and ideal selectivity (alpha CO2/CH4) has been calculated. Secondly, selectivities were calculated from mixture data by using nearly equimolar binary mixtures of both gases by a volumetric-chromatographic method to examine the IFPs. Results showed the reliability of the selectivity calculation. Values of (alpha CO2/CH4) around 7.5 for IFP-5 indicate that this material shows much better selectivities than IFP-1, IFP-2, IFP-3, IFP-4 and IFP-6 with slightly lower selectivity (alpha CO2/CH4) = 4-6. The preferred adsorption of CO2 over CH4 especially of IFP-5 and IFP-4 makes these materials suitable for gas separation application.
Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
The Low Earth Orbit (LEO) experiment Biology and Mars Experiment (BIOMEX) is an interdisciplinary and international space research project selected by ESA. The experiment will be accommodated on the space exposure facility EXPOSE-R2 on the International Space Station (ISS) and is foreseen to be launched in 2013. The prime objective of BIOMEX is to measure to what extent biomolecules, such as pigments and cellular components, are resistant to and able to maintain their stability under space and Mars-like conditions. The results of BIOMEX will be relevant for space proven biosignature definition and for building a biosignature data base (e.g. the proposed creation of an international Raman library). The library will be highly relevant for future space missions such as the search for life on Mars. The secondary scientific objective is to analyze to what extent terrestrial extremophiles are able to survive in space and to determine which interactions between biological samples and selected minerals (including terrestrial, Moon- and Mars analogs) can be observed under space and Mars-like conditions. In this context, the Moon will be an additional platform for performing similar experiments with negligible magnetic shielding and higher solar and galactic irradiation compared to LEO. Using the Moon as an additional astrobiological exposure platform to complement ongoing astrobiological LEO investigations could thus enhance the chances of detecting organic traces of life on Mars. We present a lunar lander mission with two related objectives: a lunar lander equipped with Raman and PanCam instruments which can analyze the lunar surface and survey an astrobiological exposure platform. This dual use of testing mission technology together with geo- and astrobiological analyses will significantly increase the science return, and support the human preparation objectives. It will provide knowledge about the Moon's surface itself and, in addition, monitor the stability of life-markers, such as cells, cell components and pigments, in an extraterrestrial environment with much closer radiation properties to the surface of Mars. The combination of a Raman data base of these data together with data from LEO and space simulation experiments, will lead to further progress on the analysis and interpretation of data that we will obtain from future Moon and Mars exploration missions.