Grapevine (Vitis vinifera) is susceptible to many pathogens which cause significant losses to viticulture worldwide. Chemical control is available, but agro-ecological concerns have raised interest ...in alternative methods, especially in triggering plant immunity by elicitor treatments. The β-glucan laminarin (Lam) and its sulfated derivative (PS3) have been previously demonstrated to induce resistance in grapevine against downy mildew (Plasmopara viticola). However, if Lam elicits classical grapevine defenses such as oxidative burst, pathogenesis-related (PR)-proteins and phytoalexin production, PS3 triggered grapevine resistance via a poorly understood priming phenomenon. The aim of this study was to identify the molecular mechanisms of the PS3-induced resistance. For this purpose we studied i) the signaling events and transcriptome reprogramming triggered by PS3 treatment on uninfected grapevine, ii) grapevine immune responses primed by PS3 during P. viticola infection. Our results showed that i) PS3 was unable to elicit reactive oxygen species (ROS) production, cytosolic Ca(2+) concentration variations, mitogen-activated protein kinase (MAPK) activation but triggered a long lasting plasma membrane depolarization in grapevine cells, ii) PS3 and Lam shared a common stress-responsive transcriptome profile that partly overlapped the salicylate- (SA) and jasmonate-(JA)-dependent ones. After P. viticola inoculation, PS3 specifically primed the SA- and ROS-dependent defense pathways leading to grapevine induced resistance against this biotroph. Interestingly pharmacological approaches suggested that the plasma membrane depolarization and the downstream ROS production are key events of the PS3-induced resistance.
Grapevine (Vitis vinifera L.) is susceptible to many pathogens, such as Botrytis cinerea, Plasmopara viticola, Uncinula necator, and Eutypa lata. Phytochemicals are used intensively in vineyards to ...limit pathogen infections, but the appearance of pesticide-resistant pathogen strains and a desire to protect the environment require that alternative strategies be found. In the present study, the beta-1,3-glucan laminarin derived from the brown algae Laminaria digitata was shown both to be an efficient elicitor of defense responses in grapevine cells and plants and to effectively reduce B. cinerea and P. viticola development on infected grapevine plants. Defense reactions elicited by laminarin in grapevine cells include calcium influx, alkalinization of the extracellular medium, an oxidative burst, activation of two mitogen-activated protein kinases, expression of 10 defense-related genes with different kinetics and intensities, increases in chitinase and beta-1,3-glucanase activities, and the production of two phytoalexins (resveratrol and epsilon-viniferin). Several of these effects were checked and confirmed in whole plants. Laminarin did not induce cell death. When applied to grapevine plants, laminarin reduced infection by B. cinerea and P. viticola by approximately 55 and 75%, respectively. Our data describing a large set of defense reactions in grapevine indicate that the activation of defense responses using elicitors could be a valuable strategy to protect plants against pathogens.
•In this randomized controlled trial, giving access to the interactive Sanoia e-health platform led to a small improvement in patient-perceived patient-physician interactions.•E-Health platforms are ...promising adjuncts to physician care in RA.•Although mean satisfaction with the platform was very high, around a quarter of the patients did not use the interactive platform.•Future studies of e-health should measure not only patient satisfaction but a combination of both patient satisfaction and utilization.
Sanoia is an online interactive electronic e-health platform developed to allow patient self-assessment and self-monitoring. The objective was to assess in rheumatoid arthritis (RA) patients, the efficacy on patient-physician interactions, of giving access to Sanoia.
In this French, multi-center, 12-months randomized controlled trial (CarNET: NCT02200068), patients with RA and internet access were randomized to: access without incentives to the Sanoia platform after minimal training, or usual care. The primary outcome was the change from baseline in patient-physician interactions, by the patient-reported Perceived Efficacy in Patient–Physician Interactions (PEPPI-5) questionnaire. The number of accesses to Sanoia was recorded and satisfaction with the platform was assessed through a 0–10 numeric rating scale. Analyses were in intention to treat (ITT), on SAS.
Of 320 RA patients (159 Sanoia versus 161 usual care), mean (standard deviation) age was 57.0 (12.7) years, mean (SD) disease duration was 14.6 (11.1) years, 216 (67.5%) were taking a biologic and 253 (79.1%) were female. Mean (SD) PEPPI scores at baseline and 12 months were 38.6 (8.2) and 39.2 (8.0) (delta=+0.60 5.52) versus 39.7 (7.3) and 38.8 (8.0) (delta=−0.91 6.08) in the Sanoia and control group, respectively (P=0.01). Although mean satisfaction with the platform was very high (1.46 1.52), 41 patients (25.7%) never accessed Sanoia.
Giving RA patients access to the interactive Sanoia e-health platform led to a small improvement in patient-perceived patient-physician interactions. A disjunction between patient satisfaction and access to the platform was noted. E-Health platforms are promising in RA.
•Partial hydropobization and further sulfation of native β-(1→3)-glucan.•Biological studies as defense elicitor in grapevine.•Biological studies as antimicrobial compounds against Plasmopara ...viticola.
Laminaran, a β-(1→3)-glucan extracted from Laminaria digitata, is a known elicitor of plant defenses, but provides only low level of disease control in vineyard trials. In this context, laminaran was partly hydrophobized by grafting from 1.6 to 7.6 lauryl chains to the native saccharidic chain and the impact of sulfation of the hydrophobized glucans was studied. The activity of the different synthetized laminaran derivatives as antimicrobial agents against Plasmopara viticola, the causal agent of grape downy mildew, and as elicitors of defense reactions in planta, was evaluated. Our results showed that acylation imparts an antimicrobial activity to laminaran which is related to the degree of acylation, AL3, with 7.6 lauryl chains, being the most effective derivative. Sulfation of the acylated laminarans did not further increase the antimicrobial activity. Our results also demonstrated that the efficacy of AL3 against Plasmopara viticola was most likely due to the direct antimicrobial activity of the lauryl chains rather than to an elicitation of plant defenses.
The ionic conductivity of potassium boroantimonate K3Sb4O10(BO3) is studied between 300 and 750 °C by AC complex impedance measurement. Ball-milling of the powder prepared by solid state reaction at ...high temperature increases significantly the relative density of the sintered pellet and therefore the conductivity level which is about 1.5 × 10−4 S cm−1 at 400 °C. The addition of a glass-type sintering aid increases similarly the relative density but has a detrimental effect over the conductivity level. The low activation energy of K3Sb4O10(BO3) compound, Ea = 0.325 eV, is related to the diffusion of K+ ions through interconnected 1D-tunnels.
•Ionic conductivity of potassium boroantimonate K3Sb4O10(BO3) is studied.•Ball-milling and/or addition of glass-type sintering aid improve relative density of sintered pellet.•K3Sb4O10(BO3) sintered material with 90% relative density has been achieved.•Ionic conductivity with low activation energy is related to the displacement of K+ ions through interconnected 1D-tunnels.
We report for the first time a combined experimental and computational study of oxygen ion transport and the effects of doping in Ba3Ti3O6(BO3)2, a promising oxyborate for solid-oxide fuel cell ...applications. Undoped and doped samples were prepared by solid-state reaction and characterized using X-ray diffraction and electrochemical impedance spectroscopy. We find that the undoped sample already has a conductivity level that is quite high, about 1.46 × 10–4 S cm–1 at 700 °C in air. Partial replacement of Ba2+ or Ti4+ by subvalent elements, Ba3–x A x Ti3O6(BO3)2 (A = Na+, K+) and Ba3Ti3–x M x O6 (BO3)2 (M = Mg2+, In3+, Sb3+), leads to reduced conductivity, whereas partial replacement of Ti4+ by supervalent elements, Ba3Ti3–x M x O6(BO3)2 (M = Nb5+, Ta5+), increases the conductivity. The measured activation energy is in the range 0.99–1.09 eV for the doped samples (compared to 1.02 eV of the undoped one). The transport properties can be understood in terms of the presence of oxygen and barium vacancies in high concentrations as well as oxygen interstitials as observed in hybrid density-functional defect calculations.
Cellodextrins (CD), water-soluble derivatives of cellulose composed of β-1,4 glucoside residues, have been shown to induce a variety of defence responses in grapevine (Vitis vinifera L.) cells. The ...larger oligomers of CD rapidly induced transient generation of H2O2 and elevation in free cytosolic calcium, followed by a differential expression of genes encoding key enzymes of the phenylpropanoid pathway and pathogenesis-related (PR) proteins as well as stimulation of chitinase and β-1,3 glucanase activities. Most of these defence reactions were also induced by linear β-1,3 glucans (βGlu) and α-1,4 oligogalacturonides (OGA) of different degree of polymerization (DP), but the intensity of some reactions induced by CD was different when compared with βGlu and OGA effects. Moreover, desensitization assays using H2O2 production showed that cells treated with CD remained fully responsive to a second application of OGA, suggesting a different mode of perception of these oligosaccharides by grape cells. None of CD, βGlu, or OGA induced HSR gene expression nor did they induce cell death. In accordance with elicitor activity in grapevine cells, CD-incubated leaves challenged with Botrytis cinerea also resulted in a significant reduction of the disease. Data suggest that CD could operate via other distinct reaction pathways than βGlu and OGA. They also highlight the requirement of a specific DP for each oligosaccharide to induce the defence response.
Laminarin, a linear β-1,3 glucan (mean degree of polymerization of 33) was extracted and purified from the brown alga Laminaria digitata. Its elicitor activity on tobacco (Nicotiana tabacum) was ...compared to that of oligogalacturonides with a mean degree of polymerization of 10. The two oligosaccharides were perceived by suspension-cultured cells as distinct chemical stimuli but triggered a similar and broad spectrum of defense responses. A dose of 200 μg mL-1 laminarin or oligogalacturonides induced within a few minutes a 1.9-pH-units alkalinization of the extracellular medium and a transient release of H2O2. After a few hours, a strong stimulation of Phe ammonia-lyase, caffeic acid O-methyltransferase, and lipoxygenase activities occurred, as well as accumulation of salicylic acid. Neither of the two oligosaccharides induced tissue damage or cell death nor did they induce accumulation of the typical tobacco phytoalexin capsidiol, in contrast with the effects of the proteinaceous elicitor β-megaspermin. Structure activity studies with laminarin, laminarin oligomers, high molecular weight β-1,3-1,6 glucans from fungal cell walls, and the β-1,6-1,3 heptaglucan showed that the elicitor effects observed in tobacco with β-glucans are specific to linear β-1,3 linkages, with laminaripentaose being the smallest elicitor-active structure. In accordance with its strong stimulating effect on defense responses in tobacco cells, infiltration of 200 μg mL-1 laminarin in tobacco leaves triggered accumulation within 48 h of the four families of antimicrobial pathogenesis-related proteins investigated. Challenge of the laminarin-infiltrated leaves 5 d after treatment with the soft rot pathogen Erwinia carotovora subsp. carotovora resulted in a strong reduction of the infection when compared with water-treated leaves.
The nature and structure of grafted organometallic complexes on γ-alumina are studied from a combination of experimental data (mass balance analysis, IR, NMR) and density functional theory ...calculations. The chemisorptive interactions of two complexes are analyzed and compared. The reaction of Zr(CH2 tBu)4 with alumina dehydroxylated at 500 °C gives {(AlsO)2Zr(CH2 tBu)+(tBuCH2)(Als)-}, a bisgrafted cationic complex as major surface species. The DFT calculations show that the reaction with surface hydroxyls is very exothermic and that alkyl transfer on Al atoms is favored. In contrast, W(⋮CtBu)(CH2 tBu)3 reacts with an alumina treated under identical conditions to give selectively a monografted neutral surface complex, (AlsO)W(⋮CtBu)(CH2 tBu)2. This was inferred by the evolution of 1 equiv of tBuCH3 per grafted W and the presence of remaining hydroxyls. The calculations show that the reaction of W(⋮CtBu)(CH2 tBu)3 with surface hydroxyls is in fact less exothermic and has a considerably higher activation barrier than the one of the Zr complex. Additionally, the transfer of an alkyl ligand onto an adjacent Al center is disfavored, and hence cationic species are not formed. Some ligands of this monoaluminoxy surface complex interact with remaining surface hydroxyls, which explains the complexity of the experimental NMR and IR data.
Abstract
Background
Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection.
Objectives
To evaluate the non-inferiority of efficacy and ...the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years.
Methods
Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death.
Results
In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of –6.8% (lower limit of the 95% two-sided CI: –19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred.
Conclusions
Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.
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