51 research outputs found

    Efficient and Specific Internal Cleavage of a Retroviral Palindromic DNA Sequence by Tetrameric HIV-1 Integrase

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    BACKGROUND: HIV-1 integrase (IN) catalyses the retroviral integration process, removing two nucleotides from each long terminal repeat and inserting the processed viral DNA into the target DNA. It is widely assumed that the strand transfer step has no sequence specificity. However, recently, it has been reported by several groups that integration sites display a preference for palindromic sequences, suggesting that a symmetry in the target DNA may stabilise the tetrameric organisation of IN in the synaptic complex. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the ability of several palindrome-containing sequences to organise tetrameric IN and investigated the ability of IN to catalyse DNA cleavage at internal positions. Only one palindromic sequence was successfully cleaved by IN. Interestingly, this symmetrical sequence corresponded to the 2-LTR junction of retroviral DNA circles-a palindrome similar but not identical to the consensus sequence found at integration sites. This reaction depended strictly on the cognate retroviral sequence of IN and required a full-length wild-type IN. Furthermore, the oligomeric state of IN responsible for this cleavage differed from that involved in the 3'-processing reaction. Palindromic cleavage strictly required the tetrameric form, whereas 3'-processing was efficiently catalysed by a dimer. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the restriction-like cleavage of palindromic sequences may be a general physiological activity of retroviral INs and that IN tetramerisation is strongly favoured by DNA symmetry, either at the target site for the concerted integration or when the DNA contains the 2-LTR junction in the case of the palindromic internal cleavage

    SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

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    Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

    A first update on mapping the human genetic architecture of COVID-19

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    QUELQUES ASPECTS DE LA FORMATION DE FILMS MINCES DE NITRURE DE BORE CUBIQUE OBTENUS PAR DEPOT PHYSIQUE EN PHASE VAPEUR ASSISTE PAR FAISCEAU D'IONS

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    Spécialité Mécanique et Matériaux, mention très honorableThis work concerns the study of the deposition of cubic Boron Nitride thin films on Silicon substrates by using the IBAD-PVD method. Interest of these experiments consists in the low deposition temperature (200-250°C), which is near of the limit temperature of cBN nucleation. In a first time, we have determined the cubic phase synthesis conditions and characterized the films. So, we could compare the properties of the films obtained with low and high deposition temperature. We observed the influence of different parameters on the hBN/cBN phase transition, about different opinions were found in literature. Finally we tried to improve the film/substrate adhesion by making a distinction between the cubic Boron Nitride nucleation ang growth conditions. We could show that it was possible to distinguish two steps : the nucleation step and the growth step. By changing the conditions it was possible simintaneously to improve the film adherence and the cBN content.Ce travail est consacré à l’étude de la phase cubique du Nitrure de Bore, déposée en couches minces sur des substrats de Silicium par méthode PDD-IBAD à une température de dépôt faible (200-250°) et proche de la température limite de germination du cBN. Dans un premier temps nous avons pu déterminer les conditions de synthèse de la phase cubique du Nitrure de Bore et également effectuer la caractérisation des films obtenus. Par ce biais nous pouvons comparer la qualité des films synthétisés à basse et haute température. Cette étude est complétée par l’observation des facteurs responsables de la transition de phase hBN/cBN, à propos desquels des opinions divergentes ont été recueillies dans la littérature. Enfin, dans un dernier temps, nous avons tenté d’apporter des solutions à l’obstacle principal à l’industrialisation des films de cBN, qui est la mauvaise qualité de l’adhérence des couches sur le substrat. Pour ce faire, nous avons joué sur les paramètres de dépôt en différenciant les conditions de germination et de croissance du Nitrure de Bore cubique

    Could Darboux's forces be an alternative to the dark matter/energy?

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    We investigate the possibility that the Newtonian potential becomes progressively Harmonic when distances increases, as suggested in the Friedman’equations. Transition between the two potentials is describe by the forces of Darboux. Model doesn’t need dark matter or dark energy, allows to conserve energy and angular momentum and leads to flat curves of rotation at the periphery of galaxies. Dark matter is replaced by an increasing of ratio gravitational/inertial mass linked to the modification of potential

    Dynamics of Generalized Conic Trajectories

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    a class of generalized conic curves is obtained generalizing a property of an initial conic, linked to its radius of curvature. The class possesses a large variety of well-known curves and accepts as a limiting case the logarithmic spiral curve. The determination of corresponding law of central force allows to link in the same relation the restoring, inverse square and inverse cubic forces. A geometric transformation inside the class is highlighted and results are linked with contemporary preoccupations of mathematical Physics and celestial Mechanics

    Fabrication and Thermal Budget Considerations of Advanced Ge and InP SOLES Substrates

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    The Silicon on Lattice Engineered Substrate (SOLES) platform enables monolithic integration of III-V compound semiconductor (III-V) and silicon (Si) complementary metal oxide semiconductor (CMOS) devices. The SOLES wafer provides a device quality Si-on-Insulator (SOI) layer for CMOS device fabrication and an embedded III-V device template layer which serves as a seed surface for epitaxial growth of III-V devices. In this work, different approaches for fabricating SOLES wafers comprised of Ge and InP template layers are characterized and InP-based SOLES structures are demonstrated for the first time. Ge-based SOLES are robust for long durations at temperatures up to 915°C and Ge diffusion can be controlled by engineering the oxide isolation layers adjacent to the Ge. InP SOLES structures alleviate lattice and thermal expansion mismatches between the template layer and subsequent device layers. Although allowable processing temperatures for these wafers had been expected to be higher due to the higher melting temperature of InP, high indium diffusion through the SiO[subscript 2] and InP melting actually lead to lower thermal stability. This research elucidates approaches to enhance the process flexibility and wafer integrity of Ge-based and InP-based SOLES.United States. Defense Advanced Research Projects Agency. COSMOS ProgramUnited States. Office of Naval Research (Contract N00014-07-C-0629
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