Viral surface glycoproteins, gp120 and gp41, as potential drug targets against HIV-1: Brief overview one quarter of a century past the approval of zidovudine, the first anti-retroviral drug

The first anti-HIV drug, zidovudine (AZT), was approved by the FDA a quarter of a century ago, in 1985. Currently, anti-HIV drug-combination therapies only target HIV-1 protease and reverse transcriptase. Unfortunately, most of these molecules present numerous shortcoming; such as viral resistances and adverse effects. In addition, these drugs are involved in later stages of infection. Thus, it is necessary to develop new drugs that are able to block the first steps of viral life cycle. Entry of HIV-1 is mediated by its two envelope glycoproteins: gp120 and gp41. Upon gp120 binding to cellular receptors, gp41 undergoes a series of conformational changes from a non-fusogenic to a fusogenic conformation. The fusogenic core of gp41 is a trimer-of-hairpins structure in which three C-terminal helices pack against a central trimeric-coiled coil formed by three N-terminal helices. The formation of this fusogenic structure brings the viral and cellular membranes close together, a necessary condition for membrane fusion to occur. As gp120 and gp41 are attractive targets, the development of entry inhibitors represents an important avenue of anti-HIV drug therapy. The present review will focus on some general considerations about HIV, the main characteristics of gp120, gp41 and their inhibitors, with special emphasis on the advances of computational approaches employed in the development of bioactive compounds against HIV-1 entry process

Water Condensation Zones around Main Sequence Stars

Understanding the set of conditions that allow rocky planets to have liquid water on their surface -- in the form of lakes, seas or oceans -- is a major scientific step to determine the fraction of planets potentially suitable for the emergence and development of life as we know it on Earth. This effort is also necessary to define and refine the so-called "Habitable Zone" (HZ) in order to guide the search for exoplanets likely to harbor remotely detectable life forms. Until now, most numerical climate studies on this topic have focused on the conditions necessary to maintain oceans, but not to form them in the first place. Here we use the three-dimensional Generic Planetary Climate Model (PCM), historically known as the LMD Generic Global Climate Model (GCM), to simulate water-dominated planetary atmospheres around different types of Main-Sequence stars. The simulations are designed to reproduce the conditions of early ocean formation on rocky planets due to the condensation of the primordial water reservoir at the end of the magma ocean phase. We show that the incoming stellar radiation (ISR) required to form oceans by condensation is always drastically lower than that required to vaporize oceans. We introduce a Water Condensation Limit, which lies at significantly lower ISR than the inner edge of the HZ calculated with three-dimensional numerical climate simulations. This difference is due to a behavior change of water clouds, from low-altitude dayside convective clouds to high-altitude nightside stratospheric clouds. Finally, we calculated transit spectra, emission spectra and thermal phase curves of TRAPPIST-1b, c and d with H2O-rich atmospheres, and compared them to CO2 atmospheres and bare rock simulations. We show using these observables that JWST has the capability to probe steam atmospheres on low-mass planets, and could possibly test the existence of nightside water clouds.Comment: Accepted for publication in Astronomy & Astrophysic

Mesenchymal Stem Cell Therapy Regenerates the Native Bone-Tendon Junction after Surgical Repair in a Degenerative Rat Model

BACKGROUND: The enthesis, which attaches the tendon to the bone, naturally disappears with aging, thus limiting joint mobility. Surgery is frequently needed but the clinical outcome is often poor due to the decreased natural healing capacity of the elderly. This study explored the benefits of a treatment based on injecting chondrocyte and mesenchymal stem cells (MSC) in a new rat model of degenerative enthesis repair. METHODOLOGY: The Achilles' tendon was cut and the enthesis destroyed. The damage was repaired by classical surgery without cell injection (group G1, n = 52) and with chondrocyte (group G2, n = 51) or MSC injection (group G3, n = 39). The healing rate was determined macroscopically 15, 30 and 45 days later. The production and organization of a new enthesis was assessed by histological scoring of collagen II immunostaining, glycoaminoglycan production and the presence of columnar chondrocytes. The biomechanical load required to rupture the bone-tendon junction was determined. PRINCIPAL FINDINGS: The spontaneous healing rate in the G1 control group was 40%, close to those observed in humans. Cell injection significantly improved healing (69%, p = 0.0028 for G2 and p = 0.006 for G3) and the load-to-failure after 45 days (p<0.05) over controls. A new enthesis was clearly produced in cell-injected G2 and G3 rats, but not in the controls. Only the MSC-injected G3 rats had an organized enthesis with columnar chondrocytes as in a native enthesis 45 days after surgery. CONCLUSIONS: Cell therapy is an efficient procedure for reconstructing degenerative entheses. MSC treatment produced better organ regeneration than chondrocyte treatment. The morphological and biomechanical properties were similar to those of a native enthesis

The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations

Accuracy Assessment of the ESA CCI 20M Land Cover Map: Kenya, Gabon, Ivory Coast and South Africa

This working paper presents the overall and spatial accuracy assessment of the European Space Agency (ESA) 20 m prototype land cover map for Africa for four countries: Kenya, Gabon, Ivory Coast and South Africa. This accuracy assessment was undertaken as part of the ESA-funded CrowdVal project. The results varied from 44% (for South Africa) to 91% (for Gabon). In the case of Kenya (56% overall accuracy) and South Africa, these values are largely caused by the confusion between grassland and shrubland. However, if a weighted confusion matrix is used, which diminishes the importance of the confusion between grassland and shrubs, the overall accuracy for Kenya increases to 79% and for South Africa, 75%. The overall accuracy for Ivory Coast (47%) is a result of a highly fragmented land cover, which makes it a difficult country to map with remote sensing. The exception was Gabon with a high overall accuracy of 91%, but this can be explained by the high amount of tree cover across the country, which is a relatively easy class to map

Interplay Between Electronic and Steric Effects in Multiphotochromic Diarylethenes

The structures and electronic features of five complex multiphotochromic molecules incorporating two or three diarylethene units are investigated with quantum mechanical approaches. Four out of the five systems only display partial photochromism, and it is shown that the interplay between steric and electronic effects might explain this outcome. For a spiro-bonded system (I), the doubly closed isomer is reachable because the two photochromes are essentially independent and undergo no specific geometric stress. For a tetrathiafilvalene-bridged derivative (II), there is no steric hindrance, but promoting the electron toward the reactive orbital is not possible. In dimers sharing a central thiophene ring (III and IV), the absence of the closed-closed derivative can be understood by either the compactness of the molecule or by a combination of conformational and electronic (lack of photochromic orbital) factors. Eventually, the reactivity of the trimer, V, is related to the variations of the distances between reactive carbon atoms. This contribution therefore paves the way toward an atomic-scale description of elaborated coupled switches and gives hints for the design of more efficient multiaddressable structures, by proposing a new architecture