62 research outputs found

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

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    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

    Interaction of Copper-Based Nanoparticles to Soil, Terrestrial, and Aquatic Systems: Critical Review of the State of the Science and Future Perspectives

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    In the past two decades, increased production and usage of metallic nanoparticles (NPs) has inevitably increased their discharge into the different compartments of the environment, which ultimately paved the way for their uptake and accumulation in various trophic levels of the food chain. Due to these issues, several questions have been raised on the usage of NPs in everyday life and has become a matter of public health concern. Among the metallic NPs, Cu-based NPs have gained popularity due to their cost-effectiveness and multifarious promising uses. Several studies in the past represented the phytotoxicity of Cu-based NPs on plants. However, comprehensive knowledge is still lacking. Additionally, the impact of Cu-based NPs on soil organisms such as agriculturally important microbes, fungi, mycorrhiza, nematode, and earthworms are poorly studied. This review article critically analyses the literature data to achieve a more comprehensive knowledge on the toxicological profile of Cu-based NPs and increase our understanding of the effects of Cu-based NPs on aquatic and terrestrial plants as well as on soil microbial communities. The underlying mechanism of biotransformation of Cu-based NPs and the process of their penetration into plants has also been discussed herein. Overall, this review could provide valuable information to design rules and regulations for the safe disposal of Cu-based NPs into a sustainable environment

    Native diversity buffers against severity of non-native tree invasions.

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    This is the final version. Available from Nature Research via the DOI in this record. Data availability: Data used in this study can be found in cited references for the Global Naturalized Alien Flora (GloNAF) database6 (non-native status), the KEW Plants of the World database5 (native ranges) and the Global Environmental Composite63,77 (environmental data layers). Plant trait data were extracted from Maynard et al.78. Data from the Global Forest Biodiversity Initiative (GFBI) database57 are not available due to data privacy and sharing restrictions, but can be obtained upon request via Science-I (https://science-i.org/) or GFBI (gfbinitiative.org) and an approval from data contributors.Code availability All code used to complete analyses for the manuscript is available at the following link: https://github.com/thomaslauber/Global-Tree-Invasion. Data analyses were conducted and were visualizations generated in R (v. 4.2.2), Python (v. 3.9.7), Google Earth Engine (earthengine-api 0.1.306), QGIS-LTR (v. 3.16.7) and the ETH Zurich Euler cluster.Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.Swiss National Science FoundationSwiss National Science FoundationBernina FoundationDOB Ecolog

    Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts

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