The Ccr4-Not Complex Interacts with the mRNA Export Machinery

The Ccr4-Not complex is a key eukaryotic regulator of gene transcription and cytoplasmic mRNA degradation. Whether this complex also affects aspects of post-transcriptional gene regulation, such as mRNA export, remains largely unexplored. Human Caf1 (hCaf1), a Ccr4-Not complex member, interacts with and regulates the arginine methyltransferase PRMT1, whose targets include RNA binding proteins involved in mRNA export. However, the functional significance of this regulation is poorly understood.Here we demonstrate using co-immunoprecipitation approaches that Ccr4-Not subunits interact with Hmt1, the budding yeast ortholog of PRMT1. Furthermore, using genetic and biochemical approaches, we demonstrate that Ccr4-Not physically and functionally interacts with the heterogenous nuclear ribonucleoproteins (hnRNPs) Nab2 and Hrp1, and that the physical association depends on Hmt1 methyltransferase activity. Using mass spectrometry, co-immunoprecipitation and genetic approaches, we also uncover physical and functional interactions between Ccr4-Not subunits and components of the nuclear pore complex (NPC) and we provide evidence that these interactions impact mRNA export.Taken together, our findings suggest that Ccr4-Not has previously unrealized functional connections to the mRNA processing/export pathway that are likely important for its role in gene expression. These results shed further insight into the biological functions of Ccr4-Not and suggest that this complex is involved in all aspects of mRNA biogenesis, from the regulation of transcription to mRNA export and turnover

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Performance of capillary discharge guided laser plasma wakefield accelerator

A GeV-class laser-driven plasma-based wakefield accelerator has been realized at the Lawrence Berkeley National Laboratory (LBNL). The device consists of the 40 TW high repetition rate Ti:sapphire LOASIS laser system at LBNL and a gas-filled capillary discharge waveguide developed at Oxford University. The operation of the capillary discharge guided laser plasma wakefield accelerator with a capillary of 225 μm diameter and 33 mm in length was analyzed in detail. The input intensity dependence suggests that excessive self-injection causes increased beam loading leading to broadband lower energy electron beam generation. The trigger versus laser arrival timing dependence suggests that the plasma channel parameters can be tuned to reduce beam divergence. ©2007 IEEE

Laser wakefield simulations towards development of compact particle accelerators

Laser driven wakefield accelerators produce accelerating fields thousands of times those achievable in conventional radio-frequency accelerators, offering compactness and ultrafast bunches to potentially extend the frontiers of high energy physics and enable laboratory scale ultrafast radiation sources. Realization of this potential requires understanding of accelerator physics to advance beam performance and stability, and particle simulations model the highly nonlinear, kinetic physics required. One-to-one simulations of experiments provide new insight for optimization and development of 100 MeV to GeV and beyond laser accelerator stages, and on production of reproducible and controllable low energy spread beams with improved emittance (focusability) and energy through control of injection. © 2007 IOP Publishing Ltd

Gev plasma accelerators driven in waveguides

During the last few years laser-driven plasma accelerators have been shown to generate quasi-monoenergetic electron beams with energies up to several hundred MeV. Extending the output energy of laser-driven plasma accelerators to the GeV range requires operation at plasma densities an order of magnitude lower, i.e. 1018 cm−3, and increasing the distance over which acceleration is maintained from a few millimetres to a few tens of millimetres. One approach for achieving this is to guide the driving laser pulse in the plasma channel formed in a gas-filled capillary discharge waveguide. We present transverse interferometric measurements of the evolution of the plasma channel formed and compare these measurements with models of the capillary discharge. We describe in detail experiments performed at Lawrence Berkeley National Laboratory and at Rutherford Appleton Laboratory in which plasma accelerators were driven within this type of waveguide to generate quasi-monoenergetic electron beams with energies up to 1 GeV