39 research outputs found

    Dynamique de la conductance hydraulique chez l'olivier de table (Olea europaea L., cv Meski)

    Get PDF
    Hydraulic Conductance Dynamic in Olive Table Tree (Olea europaea L. cv Meski). Cette étude expose les effets de l'aménagement des pâturages par la digue filtrante sur la dynamique de la végétation. Dans les régions sahéliennes, de nombreuses techniques sont appliquées sur les sols pour la restauration des parcours dégradés. La digue filtrante s'intéresse particulièrement aux axes de drainage ou bas-fonds en dégradation. La méthode d'étude a consisté à évaluer l'impact des digues filtrantes par l'inventaire de la végétation, la mesure de la biomasse produite, et l'analyse chimique d'échantillons de fourrage et de sol. Ces observations ont été faites à la fois sur l'espace aménagé et sur un espace témoin représentatif en deux fois durant cinq ans. Les observations sur l'espace aménagé (stations d'observation d'un ha) ont été faites en fonction du gradient par rapport à la digue filtrante tandis que sur le témoin (station d'observation d'un ha), les mesures ont été homogénéisées sur l'ensemble de la parcelle. Les résultats obtenus des inventaires de végétation montrent un effet positif de l'aménagement sur la dynamique de la végétation qui se maintient après cinq années. Les effets concernent la composition floristique pour laquelle certaines espèces connaissent une amélioration. Il s'agit de Panicum laetum (+ 5,9% en 1999 et + 1,9% en 2003), Setaria pallide fusca (+ 2,4 à + 8,6%), Cassia obtusifolia (+ 13,6% à + 9,3%) et Zornia glochidiata (- 2,9% à + 1,7 %). Les espèces en régression sont surtout composées de Schoenefeldia gracilis (+ 1,7% à - 12%) et Microchloa indica (- 28,9% à - 12,1% entre 1999 et 2003). L'écart de recouvrement du sol entre la parcelle aménagée et le témoin a été de -0,4% en 1999 contre + 14,6% en 2003. La biomasse produite et la capacité de charge ont connu une expansion allant de 3,14 à 4,5 fois par rapport à l'espace non aménagé. Cependant, des suivis doivent encore être maintenus en associant surtout les effets de l'exploitation (fauche et pâture) pour mieux préciser l'efficacité et la durabilité de ces aménagements sur les zones pastorales en même temps que des stratégies sont définies au niveau village sur la gestion de ces espaces restaurés

    In Silico Description of the Direct Inhibition Mechanism of Endothelial Lipase by ANGPTL3

    Get PDF
    Angiopoietin-like protein 3 (ANGPTL3) is a plasmatic protein that plays a crucial role in lipoprotein metabolism by inhibiting the lipoprotein lipase (LPL) and the endothelial lipase (EL) responsible for the hydrolysis of phospholipids on high-density lipoprotein (HDL). Interest in developing new pharmacological therapies aimed at inhibiting ANGPTL3 has been growing due to the hypolipidemic and antiatherogenic profile observed in its absence. The goal of this study was the in silico characterization of the interaction between ANGPTL3 and EL. Because of the lack of any structural information on both the trimeric coiled-coil N-terminal domain of ANGPTL3 and the EL homodimer as well as data regarding their interactions, the first step was to obtain the three- dimensional model of these two proteins. The models were then refined via molecular dynamics (MD) simulations and used to investigate the interaction mechanism. The analysis of interactions in different docking poses and their refinement via MD allowed the identification of three specific glutamates of ANGPTL3 that recognize a positively charged patch on the surface of EL. These ANGPTL3 key residues, i.e., Glu154, Glu157, and Glu160, could form a putative molecular recognition site for EL. This study paves the way for future investigations aimed at confirming the recognition site and at designing novel inhibitors of ANGPTL3

    PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

    Get PDF
    The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

    Get PDF
    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

    Get PDF
    Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    WATER STRESS IN TANNAT AND DURAS GRAPEVINE CULTIVARS (VITIS VINIFERA L.): LEAF PHOTOSYNTHESIS AND GRAPE PHENOLIC MATURITY

    No full text
    Our study focuses on the physiological responses and berries phenolic maturity of Tannat and Duras red wine grape cultivars, which are autochthonous from the southern France, under water stress condition from pre-véraison to harvest by limiting water availability to 30% of the control well-watered. Methode and result : Predawn and midday leaf water potentials served as an indicator to maintain water stress level compared to the control. The seasonal reduction of leaf net assimilation rate under saturating irradiance (An) under water stress over six weeks stress period versus well-watered was 60% for Tannat and Duras as compared to 64 and 46% for leaf stomatal conductance (gs) for Tannat and Duras cultivars respectively. These responses qualify Tannat as a good candidate for adapting to limited water availability. For both Tannat and Duras cultivars, relationships between the fresh mass, skin and flesh in six different berry size categories, ranged from about 0.5 to 2.0 g, were assessed on ripe fruit from grapevines subjected to well-watered and water stressed treatments. Fresh mass components for both treatments varied significantly depending on the grape cultivar and water availability. Tannat showed that seed represented around 6%, skin around 12%, and flesh about 82% of the berry total fresh weight. The Duras cultivar showed that seed represented around 3%, skin around 12% and flesh around 85%. Exact proportion of seed, skin and flesh varied according to berry size category. There was an increase in total seed mass per berry to water stress treatment. Anthocyanin content and the seed tannin concentration varied depending on the grape variety and water stress treatment. In comparison with skin tannin or anthocyanin content, seed tannin varied more with berry size and less with vine water status. Tannat variety showed a positive effect of water stress on anthocyanin content but not Duras. At last, seed and skin tannin concentrations decreased with berry fresh weight

    Effetto della disponibilita’ idrica sulla risposta eco-fisiologica e sulle caratteristiche dell’acino di quattro varieta’ autoctone della regione di “Midi-Pyrénées” in Francia.

    No full text
    In due successive stagioni vegetative è stato studiato l’effetto dello stress idrico su alcune caratteristiche eco-fisiologiche e morfologiche dell’acino di quattro varietà di vite: Côt (=Malbec), Négrette, Tannat e Duras; autoctone dell’area Sud-Ovest della Francia (Regione “Midi-Pyrénées”). All’inizio dell’invaiatura su metà delle piante di ciascuna varietà, secondo uno schema completamente randomizzato, è stato imposto uno stress idrico diminuendo del 70% i volumi irrigui utilizzati per il controllo. Dopo sei settimane, la diminuzione delle disponibilità idriche ha comportato un abbassamento, rispetto alle piante irrigate, della conduttanza stomatica e dell’assimilazione massima. La distribuzione del peso fresco dell’acino, misurata in 6 diverse categorie di dimensione degli acini, ha messo in evidenza un significativo aumento delle categorie di acino con peso inferiore ad 1.0 g nelle piante sottoposte a stress idrico rispetto a quelle ben irrigate. Gli acini sottoposti a stress idrico avevano inoltre un maggior peso relativo dei semi rispetto a buccia e polpa. La concentrazione in antociani e tannini della buccia non è stata significativamente modificata dal trattamento irriguo in Côt, Négrette mentre significativamente più elevata è stata in Tannat e Duras. La concentrazione di tannini dei semi è stata influenzata dal trattamento irriguo in relazione alla cultivar ed alla dimensione dell’acino. In definitiva la concentrazione dei tannini dei semi e della buccia decresce con l’aumentare del peso fresco dell’acino, mentre la concentrazione gli antociani della buccia è meno influenzata dalle dimensioni dell’acino e positivamente associata al deficit idrico

    In silico investigation of mAbs conformational changes upon antigen binding: impact of glycosylation and light chain isotype

    No full text
    Monoclonal antibodies (mAbs) represent a major class of biopharmaceuticals employed for the treatment of diseases such as cancer, asthma, and cardiovascular disorders. Glycosylation of mAbs, specifically occurring on the Fc region, affects their binding affinity to FcγRIIIa, with core fucosylation reducing the stability of the interaction. Additionally, the light chain (LC) isotype influences the conformational behavior of mAbs, modulating Fab rotation and Fc opening. In this study, we employed accelerated MD simulations to explore the impact of the antigen on the conformational dynamics of mAbs, focusing on how glycosylation patterns and LC isotype influence this process. Specifically, we examined two commercial antibodies differing in the LC composition, adalimumab and avelumab, in both G0 and G0F glycosylation states. Our results reveal that antigen binding induces conformational changes in the Fab and Fc regions, with glycosylation influencing the rearrangements in the Fc: G0 mAbs show an opening of the region, while G0F mAbs exhibit Fc closure. Furthermore, we observed that k-LC mAbs (adalimumab) display more extensive Fc rearrangements compared to λ-containing mAbs (avelumab), which show restricted Fc flexibility. These findings suggest that fucose and λ LC isotypes introduce structural constraints that may limit immune receptor interactions. Notably, antigen binding triggers an allosteric effect that affects distant Fc and hinge regions, whose rearrangement is crucial for the secondary mechanism of action of these molecules. Our study highlights the importance of antibody conformation in facilitating immune receptors engagement, suggesting that antigen binding in both adalimumab and avelumab enables conformational changes that might impact FcγRIIIa interaction and, therefore, antibody-dependent cellular cytotoxicity (ADCC)
    corecore