Loss of Anticodon Wobble Uridine Modifications Affects tRNALys Function and Protein Levels in Saccharomyces cerevisiae

In eukaryotes, wobble uridines in the anticodons of tRNALysUUU, tRNAGluUUC and tRNAGlnUUG are modified to 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U). While mutations in subunits of the Elongator complex (Elp1-Elp6), which disable mcm5 side chain formation, or removal of components of the thiolation pathway (Ncs2/Ncs6, Urm1, Uba4) are individually tolerated, the combination of both modification defects has been reported to have lethal effects on Saccharomyces cerevisiae. Contrary to such absolute requirement of mcm5s2U for viability, we demonstrate here that in the S. cerevisiae S288C-derived background, both pathways can be simultaneously inactivated, resulting in combined loss of tRNA anticodon modifications (mcm5U and s2U) without a lethal effect. However, an elp3 disruption strain displays synthetic sick interaction and synergistic temperature sensitivity when combined with either uba4 or urm1 mutations, suggesting major translational defects in the absence of mcm5s2U modifications. Consistent with this notion, we find cellular protein levels drastically decreased in an elp3uba4 double mutant and show that this effect as well as growth phenotypes can be partially rescued by excess of tRNALysUUU. These results may indicate a global translational or protein homeostasis defect in cells simultaneously lacking mcm5 and s2 wobble uridine modification that could account for growth impairment and mainly originates from tRNALysUUU hypomodification and malfunction.

Untersuchung der Adsorptionskinetik photoschaltbarer azobenzolfunktionalisierter selbstorganisierter Monolagen mit optischer Frequenzverdopplung

In dieser Arbeit wurde das Adsorptionsverhalten zweier azobenzolfunktionalisierter Liganden auf Goldoberflächen untersucht. Diese Liganden zeichnen sich dadurch aus, dass sie mithilfe von Licht bestimmter Wellenlängen zwischen zwei Isomerisierungszuständen – sowohl in Lösung als auch in den auf der Oberfläche resultierenden Monolage – hin und her geschaltet werden können. Somit ist es möglich, Oberflächen herzustellen, deren physikalische und chemische Eigenschaften zwischen zwei Zuständen variiert werden können. Die Messungen des Adsorptionsverhaltens wurden mittels optischer Frequenzverdopplung durchgeführt. Diese Messmethode ist höchst grenzflächensensitiv und ermöglicht es somit die Adsorption der Liganden in situ und ich Echtzeit zu verfolgen. Neben den Adsorptionsmessungen wurde auch die Phase des frequenzverdoppelten Signals über eine Interferenzmethode gemessen. Die Ergebnisse dieser Phasenmessungen ermöglichen es, eine Aussage über eine mögliche Nichtlinearität der untersuchten Moleküle zu treffen. An die in den Adsorptionsmessungen gewonnenen Messdaten wurden drei kinetische Standardmodelle angepasst. Beschreibt eines dieser Modelle den im Experiment bestimmten Adsorptionsverlauf, kann eine Aussage über die zugrunde liegenden Prozesse des Adsorptionsvorganges getroffen werden. Die Ergebnisse der Adsorptionsmessungen zeigen einen deutlichen Einfluss des Isomerisierungszustandes der Liganden auf den Verlauf der Adsorption. Liegen die Moleküle im geschalteten Zustand vor, so verläuft die Adsorption langsamer. Weiterhin konnte gezeigt werden, dass ebenso intermolekulare Wechselwirkungen über Wasserstoffbrückenbindungen einen verlangsamenden Einfluss auf die Adsorption der Liganden haben. In den durchgeführten Phasenmessungen zeigte sich darüber hinaus, dass Liganden, die über an die Azobenzolgruppe angebundene Amidgruppen verfügen, eine Nichtlinearität aufweisen. Diese Nichtlinearität ist zudem vom Isomerisierungszustand der Liganden abhängig. In den kinetischen Untersuchungen konnte darüber hinaus gezeigt werden, dass sich die Adsorption der Liganden bis auf eine Ausnahme durch die Langmuirkinetik 2. Ordnung beschreiben lässt. Somit handelt es ich bei der Adsorption der untersuchten Liganden um eine Reaktion, der eine Bindungsspaltung voran geht. Dieser Befund konnte durch Vergleich mit weiteren Experimenten bestätigt werden.

Electron-Nuclear Correlation in Laser-Driven Diatomic Molecules

The interaction of short intense laser pulses with atoms/molecules produces a multitude of highly nonlinear processes requiring a non-perturbative treatment. Detailed study of these highly nonlinear processes by numerically solving the time-dependent Schrodinger equation becomes a daunting task when the number of degrees of freedom is large. Also the coupling between the electronic and nuclear degrees of freedom further aggravates the computational problems. In the present work we show that the time-dependent Hartree (TDH) approximation, which neglects the correlation effects, gives unreliable description of the system dynamics both in the absence and presence of an external field. A theoretical framework is required that treats the electrons and nuclei on equal footing and fully quantum mechanically. To address this issue we discuss two approaches, namely the multicomponent density functional theory (MCDFT) and the multiconfiguration time-dependent Hartree (MCTDH) method, that go beyond the TDH approximation and describe the correlated electron-nuclear dynamics accurately. In the MCDFT framework, where the time-dependent electronic and nuclear densities are the basic variables, we discuss an algorithm to calculate the exact Kohn-Sham (KS) potentials for small model systems. By simulating the photodissociation process in a model hydrogen molecular ion, we show that the exact KS potentials contain all the many-body effects and give an insight into the system dynamics. In the MCTDH approach, the wave function is expanded as a sum of products of single-particle functions (SPFs). The MCTDH method is able to describe the electron-nuclear correlation effects as the SPFs and the expansion coefficients evolve in time and give an accurate description of the system dynamics. We show that the MCTDH method is suitable to study a variety of processes such as the fragmentation of molecules, high-order harmonic generation, the two-center interference effect, and the lochfrass effect. We discuss these phenomena in a model hydrogen molecular ion and a model hydrogen molecule. Inclusion of absorbing boundaries in the mean-field approximation and its consequences are discussed using the model hydrogen molecular ion. To this end, two types of calculations are considered: (i) a variational approach with a complex absorbing potential included in the full many-particle Hamiltonian and (ii) an approach in the spirit of time-dependent density functional theory (TDDFT), including complex absorbing potentials in the single-particle equations. It is elucidated that for small grids the TDDFT approach is superior to the variational approach.

Adsorption kinetic investigations of phthalocyanine derivatives self assembled monolayers (SAMs) on gold: Temperature influence on the SAM formation process and quality

The ordered nano-structured surfaces, like self-assembled monolayers (SAMs) are of a great scientific interest, due to the low cost, simplicity, and versatility of this method. SAMs found numerous of applications in molecular electronics, biochemistry and optical devices. Phthalocyanine (Pc) complexes are of particular interest for the SAM preparation. These molecules exhibit fascinating physical properties and are chemically and thermally stable. Moreover their complex structure is advantageous for the fabrication of switchable surfaces. In this work the adsorption process of Pcs derivatives, namely, subphthalocyanines (SubPcB) and terbium (2TbPc) sandwich complexes on gold has been investigated. The influence of the molecular concentration, chain length of peripheral groups, and temperature on the film formation process has been examined using a number of techniques. The SAMs formation process has been followed in situ and in real time by means of second harmonic generation (SHG) and surface plasmon resonance (SPR) spectroscopy. To investigate the quality of the SAMs prepared at different temperatures atomic force microscopy (AFM) and X-Ray photoelectron spectroscopy (XPS)measurements were performed. Valuable information about SubPcB and 2TbPc adsorbtion process has been obtained in the frame of this work. The kinetic data, obtained with SHG and SPR, shows the best conformance with the first order Langmuir kinetic model. Comparing SHG and SPR results, it has been found, that the film formation occurs faster than the formation of chemical bonds. Such, the maximum amount of molecules on the surface is reached after 6 min for SubPcB and 30 min for 2TbPc. However, at this time the amount of formed chemicals bonds is only 10% and 40% for SubPcB and 2TbPc, respectively. The most intriguing result, among others, was obtained at T = 2 °C, where the formation of the less dense SAMs have been detected with SHG.However, analyzing XPS and AFM data, it has been revealed, that there is the same amount of molecules on the surface at both temperature T = 2 °C, and T = 21 °C, but the amount of formed chemicals bond is different. At T = 2 °C molecules form aggregates, therefore many of available anchor groups stay unattached.

‘Ethical’, but Gender-Biased?

The migration of healthcare professionals from developing to developed countries, often aided by recruitment agencies, is a phenomenon of great international concern, as reflected in the construction of numerous ethical recruitment codes, which aim to govern the process. In an attempt to provide an overview of the situation, dealing specifically with the migration of nurses, as well as a critical and gender sensitive analysis of the codes, this paper follows three broad steps: first, it reviews the literature dedicated to the migration of nurses from developing to developed countries, adding a gendered account to more conventional push-pull explanations; second, it delineates the positive and negative effects that nurse migration has at the stakeholders levels of the individual, institutional, national and international level, paying particular attention to the role of gender; and third, it reviews and compares numerous codes for the ethical recruitment of nurses, highlighting the gendered rationale and consequences they may have. In showing that nurse migration is a gendered phenomenon, the paper questions whether the codes, written in gender neutral language, will come to bear unintended consequences that will effectively work to uphold gender stereotypes and inequalities.

First-principles electronic theory of non-collinear magnetic order in transition-metal nanowires

The structural, electronic and magnetic properties of one-dimensional 3d transition-metal (TM) monoatomic chains having linear, zigzag and ladder geometries are investigated in the frame-work of first-principles density-functional theory. The stability of long-range magnetic order along the nanowires is determined by computing the corresponding frozen-magnon dispersion relations as a function of the 'spin-wave' vector q. First, we show that the ground-state magnetic orders of V, Mn and Fe linear chains at the equilibrium interatomic distances are non-collinear (NC) spin-density waves (SDWs) with characteristic equilibrium wave vectors q that depend on the composition and interatomic distance. The electronic and magnetic properties of these novel spin-spiral structures are discussed from a local perspective by analyzing the spin-polarized electronic densities of states, the local magnetic moments and the spin-density distributions for representative values q. Second, we investigate the stability of NC spin arrangements in Fe zigzag chains and ladders. We find that the non-collinear SDWs are remarkably stable in the biatomic chains (square ladder), whereas ferromagnetic order (q =0) dominates in zigzag chains (triangular ladders). The different magnetic structures are interpreted in terms of the corresponding effective exchange interactions J(ij) between the local magnetic moments μ(i) and μ(j) at atoms i and j. The effective couplings are derived by fitting a classical Heisenberg model to the ab initio magnon dispersion relations. In addition they are analyzed in the framework of general magnetic phase diagrams having arbitrary first, second, and third nearest-neighbor (NN) interactions J(ij). The effect of external electric fields (EFs) on the stability of NC magnetic order has been quantified for representative monoatomic free-standing and deposited chains. We find that an external EF, which is applied perpendicular to the chains, favors non-collinear order in V chains, whereas it stabilizes the ferromagnetic (FM) order in Fe chains. Moreover, our calculations reveal a change in the magnetic order of V chains deposited on the Cu(110) surface in the presence of external EFs. In this case the NC spiral order, which was unstable in the absence of EF, becomes the most favorable one when perpendicular fields of the order of 0.1 V/Å are applied. As a final application of the theory we study the magnetic interactions within monoatomic TM chains deposited on graphene sheets. One observes that even weak chain substrate hybridizations can modify the magnetic order. Mn and Fe chains show incommensurable NC spin configurations. Remarkably, V chains show a transition from a spiral magnetic order in the freestanding geometry to FM order when they are deposited on a graphene sheet. Some TM-terminated zigzag graphene-nanoribbons, for example V and Fe terminated nanoribbons, also show NC spin configurations. Finally, the magnetic anisotropy energies (MAEs) of TM chains on graphene are investigated. It is shown that Co and Fe chains exhibit significant MAEs and orbital magnetic moments with in-plane easy magnetization axis. The remarkable changes in the magnetic properties of chains on graphene are correlated to charge transfers from the TMs to NN carbon atoms. Goals and limitations of this study and the resulting perspectives of future investigations are discussed.