LEDGF/p75 Proteins with Alternative Chromatin Tethers Are Functional HIV-1 Cofactors

LEDGF/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear. While a single integrase binding domain (IBD) binds integrase, a complex N-terminal domain ensemble (NDE) interacts with unknown chromatin ligands. Whether integration requires chromatin tethering per se, specific NDE-chromatin ligand interactions or other emergent properties of LEDGF/p75 has been elusive. Here we replaced the NDE with strongly divergent chromatin-binding modules. The chimeras rescued integrase tethering and HIV-1 integration in LEDGF/p75-deficient cells. Furthermore, chromatin ligands could reside inside or outside the nucleosome core, and could be protein or DNA. Remarkably, a short Kaposi's sarcoma virus peptide that binds the histone 2A/B dimer converted GFP-IBD from an integration blocker to an integration cofactor that rescues over two logs of infectivity. NDE mutants were corroborative. Chromatin tethering per se is a basic HIV-1 requirement and this rather than engagement of particular chromatin ligands is important for the LEDGF/p75 cofactor mechanism

Review of the late Quaternary stratigraphy of the northern Gulf of Cadiz continental margin:New insights into controlling factors and global implications

Over the past decades, the northern Gulf of Cadiz has been the focus of a wide range of late Quaternary seismic and sequence stratigraphic studies, either addressing the slope contourite depositional system (CDS), or the development of the continental shelf. Yet, high-resolution seismic data bridging between these domains and age information have remained sparse. This study, based on new high-resolution reflection seismic profiles calibrated to IODP Expedition 339 sites U1386/U1387, now presents an updated stratigraphic framework, that integrates (for the first time) the late Quaternary records of the northern Gulf of Cadiz middle slope to shelf off the Guadiana River. Seismic stratigraphic analysis of the stacking, depocenter distribution, stratal architecture and facies of the seismic (sub-)units reveals the influence of similar to 100 kyr sea-level variations paced by Milankovitch (eccentricity) cycles, tectonics (manifesting as two pulses of uplift and margin progradation), sediment supply and bottom current activity. This work furthermore contributes to the application and understanding of high-resolution, late Quaternary sequence stratigraphy. Firstly, the proposed sequence stratigraphic interpretation shows that adaptations to the basic models are required to integrate the shelf and slope record, and to account for the presence of a significant alongslope (bottom current-controlled) component. Secondly, the results confirm that the sequences are dominantly composed of regressive deposits, whereas the preservation of transgressive to highstand deposits is more irregular. Significantly, the common assumption that successive major glacial lowstands are consistently recorded as well-marked, shelf-wide erosional unconformities, is demonstrated to be occasionally invalid, as tectonics can obliterate this one-to-one relationship

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

Nucleolus: the fascinating nuclear body

Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed

Fitoplancton y variables ambientales en cauces del Paranà Medio, Argentina : analisis de correlacion canonica = Le phytoplancton et son environnement dans les cours d'eau du Moyen Paranà, Argentine : analyse canonique

Trois applications de l'analyse canonique (deux campagnes groupées et chacune séparément) ont porté sur les variables de l'environnement (débit, conductivité, pH et O2 dissous) et les caractéristiques du phytoplancton total (#Euchlorophyceae, Cyanophyceae, Euglenophyceae, Dynophyceae, Cryptomonas pl. sp., #Cyclotella pl. sp. et #Melosira pl. sp.). Les données proviennent de 25 stations de différents cours d'eau du Parana Moyen, lit principal, chenaux secondaires et affluents, pour un niveau moyen (décembre 1981) et un niveau de l'eau (mars-avril 1982) ... On a montré ainsi que l'analyse canonique de rang 1 permet d'identifier les caractères écologiques du milieu, et indique que l'implantation prévue du barrage sur le Parana Moyen risque d'augmenter le phytoplancton total, et en particulier les #Euglenophyceae, Euchlorophyceae et #Melosira$, aussi bien dans la retenue qu'en ava

Fitoplancton y variables ambientales en cauces del Paranà Medio, Argentina : analisis de correlacion canonica = Le phytoplancton et son environnement dans les cours d'eau du Moyen Paranà, Argentine : analyse canonique

Trois applications de l'analyse canonique (deux campagnes groupées et chacune séparément) ont porté sur les variables de l'environnement (débit, conductivité, pH et O2 dissous) et les caractéristiques du phytoplancton total (#Euchlorophyceae, Cyanophyceae, Euglenophyceae, Dynophyceae, Cryptomonas pl. sp., #Cyclotella pl. sp. et #Melosira pl. sp.). Les données proviennent de 25 stations de différents cours d'eau du Parana Moyen, lit principal, chenaux secondaires et affluents, pour un niveau moyen (décembre 1981) et un niveau de l'eau (mars-avril 1982) ... On a montré ainsi que l'analyse canonique de rang 1 permet d'identifier les caractères écologiques du milieu, et indique que l'implantation prévue du barrage sur le Parana Moyen risque d'augmenter le phytoplancton total, et en particulier les #Euglenophyceae, Euchlorophyceae et #Melosira$, aussi bien dans la retenue qu'en ava