Antihypertensive Drug Guanabenz Is Active In Vivo against both Yeast and Mammalian Prions

Background: Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans. [br/] Methodology/Principal Findings: Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of a2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrPSc clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on a2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals. [br/] Conclusion/Significance: GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases

A convenient approach to the synthesis of medium size oligodeoxyribonucleotides by improved new phosphite method.

Improvement of the new phosphite method for the synthesis of oligodeoxyribonucleotides using the deoxyribonucleoside 3'-bis(1,1,1,3,3,3- hexafluoro-2-propyl) phosphite unit has been carried out via the hydrolysis and capping steps, without any side reaction products. The new phosphite unit and capping agent, bis(1,1,1,3,3,3-hexafluoro-2-propyl)-2-propyl phosphite, is readily activated by N-methylimdazole under very mild condition on a solid support. This operation involves a one pot reaction, which is an advantage over both the phosphite and H- phosphonate approaches. The mechanism of internucleotidic bond formation of the new phosphite method is also discussed

Two-photon excitation in the life sciences: From observation to action

International audienceTwo-photon (TP) excitation of organic chromophores is of great interest for decades, as applications of such phenomena from 3-dimentional (3D) microfabrication to optical limiting and optical data storage, are of increasing importance. More recently, two-photon excitation found important applications in biology, notably in two-photon excited microscopy (TPEM) or two-photon photodynamic therapy (2P-PDT). Nevertheless, these techniques were using dyes or sensitizers designed for one-photon processes with low two-photon response. The lack of efficient molecules specifically designed for two-photon applications has led us to design new chromophores for biological applications with increased sensitivity to two-photon excitation and specifically added properties useful in biological media, such as water solubility. Here we describe the molecular engineering of such dyes mainly for cell and small animal observation by TPEM and their conjugation to magnetic nanoparticles and bio-nanoparticles such as viruses.We will then focus on the possibility to use photochemical reaction for cell triggering by two-photon photorelease of biologically active substances the so-called two-photon uncaging

Possibility and design of resonant terahertz emitters based on nanoscale strained silicon plasma wave transistors with enhanced mobility

In this paper, we report the possibility of silicon (Si) plasma wave transistor (PWT) as a resonant terahertz (THz) emitter based on the theoretical analysis focusing on the strained Si with enhanced mobility. Under asymmetric boundary conditions for plasma wave instability, the amplitude of plasma wave in FET channel increases and this plasma wave increment provides the basis of the electromagnetic (EM) wave emission from FET. Because this instability is controlled by manipulation of plasma wave velocity (s) and electron drift velocity (v0), we propose the design window based on s-v0 plot which determines whether the device operates as the resonant THz emitters considering all the required physical conditions. It is expected from the proposed design window that strained Si PWT down to 10nm gate length with enhanced channel mobility of 500cm2??V -1??-1 can operate as a resonant emitter in THz frequency range.close1