APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells

Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for viral spread and as a viral reservoir. Yet, cells of this lineage generally resist HIV-1 infection when compared to cells of other lineages, a phenomenon particularly acute during the early phases of infection. Here, we explore the role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that is highly expressed in myeloid cells, but so far lacks a known antiviral effect against retroviruses. Using ectopic expression of APOBEC3A in established cell lines and specific silencing in primary macrophages and dendritic cells, we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1, specifically in cells of myeloid origins. In these cells, APOBEC3A affects the amount of vDNA synthesized over the course of infection. The susceptibility to the antiviral effect of APOBEC3A is conserved among primate lentiviruses, although the viral protein Vpx coded by members of the SIVSM/HIV-2 lineage provides partial protection from APOBEC3A during infection. Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells. The findings presented here open up new venues on the role of APOBEC3A during HIV infection and pathogenesis, on the role of the cellular context in the regulation of the antiviral activities of members of the APOBEC3 family and more generally on the natural functions of APOBEC3A

Operational Research: Methods and Applications

Throughout its history, Operational Research has evolved to include a variety of methods, models and algorithms that have been applied to a diverse and wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first aims to summarise the up-to-date knowledge and provide an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion. It should be used as a point of reference or first-port-of-call for a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order

ARTEFACTS: How do we want to deal with the future of our one and only planet?

The European Commission’s Science and Knowledge Service, the Joint Research Centre (JRC), decided to try working hand-in-hand with leading European science centres and museums. Behind this decision was the idea that the JRC could better support EU Institutions in engaging with the European public. The fact that European Union policies are firmly based on scientific evidence is a strong message which the JRC is uniquely able to illustrate. Such a collaboration would not only provide a platform to explain the benefits of EU policies to our daily lives but also provide an opportunity for European citizens to engage by taking a more active part in the EU policy making process for the future. A PILOT PROGRAMME To test the idea, the JRC launched an experimental programme to work with science museums: a perfect partner for three compelling reasons. Firstly, they attract a large and growing number of visitors. Leading science museums in Europe have typically 500 000 visitors per year. Furthermore, they are based in large European cities and attract local visitors as well as tourists from across Europe and beyond. The second reason for working with museums is that they have mastered the art of how to communicate key elements of sophisticated arguments across to the public and making complex topics of public interest readily accessible. That is a high-value added skill and a crucial part of the valorisation of public-funded research, never to be underestimated. Finally museums are, at present, undergoing something of a renaissance. Museums today are vibrant environments offering new techniques and technologies to both inform and entertain, and attract visitors of all demographics.JRC.H.2-Knowledge Management Methodologies, Communities and Disseminatio

Spoznanja iz terenskih testov nekaterih možnostih nestabilnih pobočij v Švici

Rain-induced slope instability is a significant natural hazard in Switzerland, Slovenia and elsewhere in Europe. This contribution was prepared especially for the 12th Šuklje Symposium, and recognises that landslides occur both in mountain regions as well as in lowland regions during and following extreme-rainfall conditions. The Institute (and Professorship) for Geotechnical Engineering at the Swiss Federal Institute of Technology (ETH Zürich) has been engaged over several years in projects concerned with the characterisation, monitoring and modelling behaviour of slopes in mainly granular porous media across the full range of altitudes in Switzerland. A link is made to the doyen of the Šuklje day and then three case histories are presented and discussed to demonstrate the principal reactions to seasonal rainfall. A small slip was released in two of these cases and the “triggering” factors have been investigated and are discussed in this contribution. It transpires that the mode of inslope drainage influences the way in which the ground saturates and hence the volume of the potentially unstable ground. Simple stability analyses using limit equilibrium and soil parameters that have been amended to account for unsaturated soil behaviour were found to function well for slopes in largely granular media.Nestabilnost pobočij, ki jih povzroča dež, predstavlja pomembno ogroženost v Švici, Sloveniji in drugod po Evropi. Ta prispevek je bil še posebej pripravljen za 12. Šukljetove dneve in prikazuje takšne plaziščne pojave v hribovitih območjih, kot tudi v nižinskih predelih v času med in po izjemnimi nalivnimi pogoji. Inštitut (in profesorji) za geotehniško inženirstvo pri švicarskem Zveznem inštitutu za tehnologijo (ETH Zürich) je bil več let vključen v projekte, ki so se ukvarjali z opisom lastnosti, monitoringom in modeliranjem obnašanja pobočij, zlasti v poroznem zrnastem mediju na širokih predelih nadmorskih višin v Švici. V prispevku je povezano delo doajena Šukljetovega dne z obravnavo nestabilnosti pobočij, tej pa sledi predstavitev treh primerov plazov ter razlaga njihovega odziva na sezonsko deževje. V dveh izmed teh treh primerov je prišlo do sprožitve malega zdrsa, za katera so bili preiskani sprožilni dejavniki, ki so predstavljeni v prispevku. Le-ti so se zgodili zaradi načina drenažnega delovanja v pobočju tako, da so se tla nasičila in zaradi tega je nastala obsežna možnostna nestabilnost tal. Preprosta stabilnostna analiza z uporabo mejnega ravnovesja in z izboljšavo zemeljskih parametrov za nezasičene zemljine je bila najdena funkcija, ki je dobra za pobočja, predvsem z zrnastim medijem

Dynamic spin filtering at the Co/Alq3 interface mediated by weakly coupled second layer molecules

Spin filtering at organic-metal interfaces is often determined by the details of the interaction between the organic molecules and the inorganic magnets used as electrodes. Here we demonstrate a spin-filtering mechanism based on the dynamical spin relaxation of the long-living interface states formed by the magnet and weakly physisorbed molecules. We investigate the case of Alq3 on Co and, by combining two-photon photoemission experiments with electronic structure theory, show that the observed long-time spin-dependent electron dynamics is driven by molecules in the second organic layer. The interface states formed by physisorbed molecules are not spin-split, but acquire a spin-dependent lifetime, that is the result of dynamical spin-relaxation driven by the interaction with the Co substrate. Such spin-filtering mechanism has an important role in the injection of spin-polarized carriers across the interface and their successive hopping diffusion into successive molecular layers of molecular spintronics devices.The experimental work carried out at the University of Kaiserslautern was partly funded by the SFB/TRR 173 Spin+X: spin in its collective environment (Project B05) from the DFG. A.D. and I.R. were sponsored by the European Union through the FP7 project 618082 ACMOL. S.S. acknowledges the European Research Council, Quest project, for financial support. P.T. and B.S. thankfully acknowledge financial support from the Graduate School of Excellence MAINZ (Excellence Initiative DFG/GSC 266).Peer reviewe