Biostimulant seed treatment to enhance germination, symbiosis establishment and early growth of soybean subjected to low temperature

International audienc

Biostimulant seed treatment to enhance germination, symbiosis establishment and early growth of soybean subjected to low temperature

International audienc

Étude de l'effet de deux biostimulants sur le protéome du soja

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Peripheral but not axial muscle mass is associated with early mortality in bone metastatic lung cancer patients at diagnosis

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Venoms in drug discovery: a case study on voltage-gated channels

International audienceAmong all chemical modalities available in ion channel drug discovery, venoms are very attractive for identifying potent and selective compounds for almost all subunits of this therapeutic target family. Here, we describe a highthroughput approach for the identification and characterization of voltage-gated modulators from a large venom collection. Using this strategy, we were able to describe different mechanism of actions of subfractions and in particular antagonists of the Nav1.7 channel subunit. These results are illustrated with the characterization of the first peptide isolated from the Cyriopagopus schioedtei spider. This peptide, named cyriotoxin-1a (CyrTx-1a), is composed of 33 amino acids, contains the ICK structural motif and inhibited hNav1.1-1.3 and 1.6-1.7 in the low nanomolar range, compared to the micromolar range for hNaV1.4-1.5 and 1.8. In agreement, CyrTx-1a was 635 times more efficient at inhibiting tetrodotoxin (TTX)-sensitive than TTX-resistant sodium currents recorded from adult mouse dorsal root ganglia neurons. Within a narrow therapeutic window of concentration, CyrTx-1a exhibited an analgesic-like effect in mice by increasing reaction time in the hot plate assay and decreasing tactile sensitivity in automated plantar von Frey experiments. Finally, in vivo electrophysiological experiments showed that CyrTx-1a was approximately 170 times less efficient than huwentoxin-IV at altering mouse skeletal neuromuscular excitability properties. This pharmacological profile paves the way for further engineering studies aimed at optimizing the potential antinociceptive properties of CyrTx-1a. We will conclude by discussing these results in the context of an integrated drug discovery research platform

Rapid phosphorylation of a 27 kDa protein induced by tumor necrosis factor.

Tumor necrosis factor (TNF) has been shown to induce the phosphorylation of a 27 kDa protein in a time- and concentration-dependent manner in HeLa D98/AH2, ME 180 and bovine aortic endothelial cells. This phosphorylation could be reproduced by the calcium ionophore, A23187. However, this phosphorylation was not observed in L929 cells, for which TNF is highly cytotoxic, suggesting that it might play a role in actions of TNF other than the induction of cell death.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Design of crotoxin-based peptides with potentiator activity targeting the ΔF508NBD1 Cystic Fibrosis Transmembrane Conductance Regulator

International audienceWe have previously shown that the CBb subunit of crotoxin, a β-neurotoxin with phospholipase A2 (PLA2) activity, targets the human ΔF508CFTR chloride channel implicated in cystic fibrosis (CF). By direct binding to the nucleotide binding domain 1 (NBD1) of ΔF508CFTR, this neurotoxic PLA2 acts as a potentiator increasing chloride channel current and corrects the trafficking defect of misfolded ΔF508CFTR inside the cell. Here, for a therapeutics development of new anti-cystic fibrosis agents, we use a structure-based in silico approach to design peptides mimicking the CBb-ΔF508NBD1 interface. Combining biophysical and electrophysiological methods, we identify several peptides that interact with the ΔF508NBD1 domain and reveal their effects as potentiators on phosphorylated ΔF508CFTR. Moreover, protein-peptide interactions and electrophysiological studies allowed us to identify key residues of ΔF508NBD1 governing the interactions with the novel potentiators. The designed peptides bind to the same region as CBb phospholipase A2 on ΔF508NBD1 and potentiate chloride channel activity. Certain peptides also show an additive effect towards the clinically approved VX-770 potentiator. The identified CF therapeutics peptides represent a novel class of CFTR potentiators and illustrate a strategy leading to reproducing the effect of specific protein-protein interactions

Multi-scale study of a living yeast-based biostimulant effect on soybean

International audienceUsing biostimulants to improve crop productivity and soil fertility represent a promising agroecological practice, contributing to reduce the dependency on chemical inputs or to mitigate abiotic stresses. In a context of self-sufficiency towards plant protein for alimentation, the rise of protein crops constitutes an important issue in Europe. Soybean draws special attention because of multiple agronomic benefits and outputs. However, soybean deployment is often constrained by pedoclimatic conditions. Here, a greenhouse experiment was carried out to evaluate the potential benefit of a seed-coating treatment with a living yeast-based biostimulant on soybean. A global promotion of plant growth was observed, with a stimulation of nodulation. A multi-scale study, from plant to soil microbiome, was achieved to explore involved mechanisms of action. A proteomic analysis was performed on soybean leaves and roots collected at VC and V5 stages. This analysis showed a higher abundance of proteins involved in several pathways, such as the biosynthesis of secondary metabolites and energy metabolism for treated plants. In parallel, a transitory increase of soil microbial abundance was observed at V2 stage. Relative abundances of some bacterial and fungal genera were significantly modified at V2 and V5 stages. Microbial enzymatic activities linked to C and P cycles were enhanced whereas the one involved in N cycle was decreased at V5 stage. These results highlighted the value of living yeast-based biostimulant to sustain soybean growth. This work also emphasized the interest to consider the entire holobiont – plant with associated microbiome - to better understand the action of biostimulants