Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process

Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EV

Bio-inspired nanocatalysts for the oxygen reduction reaction

Electrochemical conversions at fuel cell electrodes are complex processes. In particular, the oxygen reduction reaction has substantial overpotential limiting the electrical power output efficiency. Effective and inexpensive catalytic interfaces are therefore essential for increased performance. Taking inspiration from enzymes, earth-abundant metal centres embedded in organic environments present remarkable catalytic active sites. Here we show that these enzyme-inspired centres can be effectively mimicked in two-dimensional metal-organic coordination networks self-assembled on electrode surfaces. Networks consisting of trimesic acid and bis-pyridyl-bispyrimidine coordinating to single iron and manganese atoms on Au(111) effectively catalyse the reduction and reveal distinctive catalytic activity in alkaline media. These results demonstrate the potential of surface-engineered metal-organic networks for electrocatalytic conversions. Specifically designed coordination complexes at surfaces inspired by enzyme cofactors represent a new class of nanocatalysts with promising applications in electrocatalysis.Fil: Grumelli, Doris Elda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Max Planck Institute for Solid State Research; AlemaniaFil: Wurtser, Benjamin. Max Planck Institute for Solid State Research; AlemaniaFil: Stepanow, Sabastian. Max Planck Institute for Solid State Research; AlemaniaFil: Kern, Klaus. Max Planck Institute for Solid State Research; Alemania. Ecole Polytechnique Federale de Lausanne; Suiz

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

A multiplatform approach identifies miR-152-3p as a common epigenetically regulated onco-suppressor in prostate cancer targeting TMEM97

Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. MicroRNAs are globally downregulated in PCa, especially in poorly differentiated tumors. Nonetheless, the underlying mechanisms are still elusive. Herein, using combined analysis of microRNAs expression and genomewide DNA methylation, we aimed to identify epigenetically downregulated microRNAs in PCa.Research Center of Portuguese Oncology Institute of Porto (FB-GEBC-27 and 19-CI-IPOP-2016). JR-C and CSG are supported by FCT- Fundação para a Ciência e Tecnologia PhD fellowships (SFRH/BD/71293/2010 and SFRH/BD/92786/2013), SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027, and IG is a research fellow from the strategic funding of FCT (PCT: PEst- UID/DTP/00776/2013 and COMPETE: POCI-01-0145-FEDER-006868). BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012)info:eu-repo/semantics/publishedVersio

Alignment of the ALICE Inner Tracking System with cosmic-ray tracks

37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe