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Aims: We investigated N471D WASH complex subunit strumpellin (Washc5) knock-in and Washc5 knock-out mice as models for hereditary spastic paraplegia type 8 (SPG8). Methods: We generated heterozygous and homozygous N471D Washc5 knock-in mice and subjected them to a comprehensive clinical, morphological and laboratory parameter screen, and gait analyses. Brain tissue was used for proteomic analysis. Furthermore, we generated heterozygous Washc5 knock-out mice. WASH complex subunit strumpellin expression was determined by qPCR and immunoblotting. Results: Homozygous N471D Washc5 knock-in mice showed mild dilated cardiomyopathy, decreased acoustic startle reactivity, thinner eye lenses, increased alkaline phosphatase and potassium levels and increased white blood cell counts. Gait analyses revealed multiple aberrations indicative of locomotor instability. Similarly, the clinical chemistry, haematology and gait parameters of heterozygous mice also deviated from the values expected for healthy animals, albeit to a lesser extent. Proteomic analysis of brain tissue depicted consistent upregulation of BPTF and downregulation of KLHL11 in heterozygous and homozygous knock-in mice. WASHC5-related protein interaction partners and complexes showed no change in abundancies. Heterozygous Washc5 knock-out mice showing normal WASHC5 levels could not be bred to homozygosity. Conclusions: While biallelic ablation of Washc5 was prenatally lethal, expression of N471D mutated WASHC5 led to several mild clinical and laboratory parameter abnormalities, but not to a typical SPG8 phenotype. The consistent upregulation of BPTF and downregulation of KLHL11 suggest mechanistic links between the expression of N471D mutated WASHC5 and the roles of both proteins in neurodegeneration and protein quality control, respectively.
The ultrafast structural dynamics of water following inner-shell ionization is a crucial issue in high-energy radiation chemistry. We have exposed isolated water molecules to a short x-ray pulse from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we can image dissociation dynamics of individual molecules in unprecedented detail. We reveal significant molecular structural dynamics in H2O2+, such as asymmetric deformation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. We thus reconstruct several snapshots of structural dynamics at different time intervals, which highlight dynamical patterns that are relevant as initiating steps of subsequent radiation-damage processes.
Following structural dynamics in real time is a fundamental goal towards a better understanding of chemical reactions. Recording snapshots of individual molecules with ultrashort exposure times is a key ingredient towards this goal, as atoms move on femtosecond (10−15 s) timescales. For condensed-phase samples, ultrafast, atomically resolved structure determination has been demonstrated using X-ray and electron diffraction. Pioneering experiments have also started addressing gaseous samples. However, they face the problem of low target densities, low scattering cross sections and random spatial orientation of the molecules. Therefore, obtaining images of entire, isolated molecules capturing all constituents, including hydrogen atoms, remains challenging. Here we demonstrate that intense femtosecond pulses from an X-ray free-electron laser trigger rapid and complete Coulomb explosions of 2-iodopyridine and 2-iodopyrazine molecules. We obtain intriguingly clear momentum images depicting ten or eleven atoms, including all the hydrogens, and thus overcome a so-far impregnable barrier for complete Coulomb explosion imaging—its limitation on molecules consisting of three to five atoms. In combination with state-of-the-art multi-coincidence techniques and elaborate theoretical modelling, this allows tracing ultrafast hydrogen emission and obtaining information on the result of intramolecular electron rearrangement. Our work represents an important step towards imaging femtosecond chemistry via Coulomb explosion.
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential K-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.
Ultrashort x-ray pulses from free-electron lasers can efficiently charge up and trigger the full fragmentation of molecules. By coincident detection of up to five ions resulting from rapid Coulomb explosion of highly charged iodomethane, we show that the full three-dimensional equilibrium geometry of this prototypical polyatomic system can be determined from the measured ion momenta with the help of a charge buildup model. Supported by simulations of how the ion momenta would reflect specific changes in molecular bond lengths and angles, we demonstrate that Coulomb-explosion imaging with ultrashort x-ray pulses is a promising technique for recording movies of multidimensional nuclear wave packets, including hydrogen motions.
During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.
We report on a multiparticle coincidence experiment performed at the European X-ray Free-Electron Laser at the Small Quantum Systems instrument using a COLTRIMS reaction microscope. By measuring two ions and two electrons in coincidence, we investigate double core-hole generation in O2 molecules in the gas phase. Single-site and two-site double core holes have been identified and their molecular-frame electron angular distributions have been obtained for a breakup of the oxygen molecule into two doubly charged ions. The measured distributions are compared to results of calculations performed within the frozen- and relaxed-core Hartree-Fock approximations.
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential 𝐾-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.
Neurowissenschaftler fordern einen illusionslosen Umgang mit Begriffen wie Willensfreiheit und Bewusstsein. Philosophen kritisieren offen die Thesen von Hirnforschern. Stehen sich diese Positionen unversöhnlich gegenüber? Wo gibt es Möglichkeiten einer Annäherung, gar einer Kooperation? Der Religionsphilosoph Prof. Dr. Thomas M. Schmidt und der Biologe Stefan Kieß loten die Situation in Frankfurt aus; ihre Gesprächspartner sind der Hirnforscher Prof. Dr. Wolf Singer (links), Direktor am Max-Planck-Institut für Hirnforschung, und Prof. Dr. Marcus Willaschek (rechts), Philosoph an der Universität Frankfurt.
Voraussetzung für die Entwicklung von Schutzstrategien für den Pflanzenartenschutz ist die Kenntnis über die Verteilung der Zentren der Artenvielfalt im Raum. Je nach Einbürgerungsstatus und Gefährdungssituation kommt verschiedenen Artengruppen dabei eine unterschiedliche Bedeutung zu. In der vorliegenden Studie werden für die Gesamtfläche der Bundesländer Niedersachsen und Bremen die im Niedersächsischen Pflanzenarten-Erfassungsprogramm (1982–2003) auf Messtischblatt-Quadranten- Ebene erhobenen Verbreitungsdaten von Gefäßpflanzensippen unter Berücksichtigung der Gesamtflorenliste (1.819 Sippen), ihres Einbürgerungsstatus (1.509 Indigene, 160 Archäophyten, 145 etablierte Neophyten) und ihrer Gefährdungssituation (ungefährdete und gefährdete Arten; davon 643 Sippen mit Rote-Liste-Status 1, 2, 3, G oder R) ausgewertet. Auf Basis der Gesamtliste ergibt sich eine inhomogene Verteilung der Sippendichte im Gesamtuntersuchungsraum, wobei die standörtlich relativ homogene Küste sowie das Tiefland – mit Ausnahme der großen Stromtäler (Weser, Aller, Elbe) – relativ artenarm sind und das standörtlich sehr heterogene Hügel- und Bergland grundsätzlich die höchsten Sippendichten aufweist. Unter Berücksichtigung des Einbürgerungsstatus zeigen die Archäophyten jeweils die größten Überschneidungsbereiche zu den Indigenen und etablierten Neophyten. Die Verbreitungsmuster der großen Gruppe der Indigenen ähneln denen der Gesamtliste, während sich die Archäophyten auf den Bremer Küstenraum, das Weser-Aller-Flachland, die Börden und das südliche Weser-Leine-Bergland konzentrieren. Die Zentren der Sippenvielfalt der etablierten Neophyten liegen vor allem in städtischen Ballungsräumen und erscheinen oftmals sehr punktuell. Die Rote-Liste-Arten sind in der Mehrzahl indigen (91 %), 8 % von ihnen sind Archäo-, nur 1 % Neophyten. Ihre Diversitätszentren sind außerordentlich differenziert: An der Küste gehören nur die isoliert liegenden Nordsee- Inseln dazu, während im Tiefland das Wendland, die Lüneburger Heide und das Elbe-Weser-Dreieck großflächige Diversitätszentren aufweisen. Im Hügel- und Bergland finden sich vor allem im Raum Göttingen, dem Weserbergland und am Harzrand gut abgegrenzte Zentren der Rote-Liste-Artendiversität. Viele dieser bedrohten Sippen sind vermutlich Spezialisten, die an natürliche oder naturnahe Habitate angepasst und somit nur in den wenigen Landschaftsbereichen anzutreffen sind, die die entsprechenden Habitatbedingungen bieten.
