Tweeting From the Moon

Lunar Communications Pathfinder is planned to enable small and large satellites and landers to carry out data intensive missions around the moon, without the need for complex and costly on-board communication equipment and access to global ground networks. From the middle of this decade there are expected to be 5 to 15 active space missions on or around the moon, generating several GBytes of data per day. Lunar Communications Pathfinder is a commercial initiative with ESA and NASA as anchor tenants. The 300kg class small spacecraft is currently in manufacture for launch in 2025, and is aimed at alleviating pressure on the Deep Space Network. It will provide a commercial high speed communications service that will enable landers, orbiters, and even CubeSats to operate around the moon without requiring direct line of sight with the Earth. A small user terminal is in development as part of the service package, and a mission builder tool has been made available for planning purposes for prospective users. LCP provides a high speed intersatellite link back to Earth for a planned 8 year mission. The system is planned to be extended further with additional spacecraft, opening up the potential to provide a more comprehensive communications and navigation service. Building on LCP, the ESA Moonlight initiative has contracted a study phase in order to develop the plans for the full constellation service beyond this initial spacecraft. LCP demonstrates how small satellites can provide innovative commercial services, and enable the ability for other small satellites and landers to carry out data intensive missions. This paper will detail the spacecraft, the system design trades, and how the service is expected to evolve

Resistance to the CCR5 Inhibitor 5P12-RANTES Requires a Difficult Evolution from CCR5 to CXCR4 Coreceptor Use

Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC) or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16–18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a “resistant” variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching

Radiofármacos PET

Dada la tasa actual de evolución de la biología molecular de los receptores del SNC, la diferencia entre el número de radiotrazadores disponibles y las drogas potenciales va creciendo rápidamente99. Debemos por tanto insistir en que la utilidad de la tecnología PET en la búsqueda de nuevos agentes terapéuticos descansa sin duda en la obtención de compuestos marcados, por lo que la potenciación de la radioquímica y la radiofarmacia van a ser puntos clave en el desarrollo de este apasionante campo