The role of hydraulics FSPMs in the context of root breeding : a case study on Pearl Millet

Developing a sustainable agricultural model is one of the great challenges of the coming years. The agricultural practices inherited from the Green Revolution of the 1960s show their limits today, and new paradigms need to be explored in the context of counter rising issues such as the multiplication of climate-change related drought episodes. Two such new paradigms are the use of functional-structural plant models to complement and rationalize breeding approaches and a renewed focus on root systems as untapped sources of plant improvement. Since the late 1980s, numerous functional and structural models of root systems were developed and used to investigate the properties of root systems in soil or lab-conditions. In this talk, we present a review on the use of multiscale functional-structural hydraulic root models in the context of drought tolerance breeding. We discuss how root models predictions can be linked to breeding studies to improve plant resistance to drought and how they can be validated to demonstrate models reliability and use. To illustrate this topic, we present a new structural model of pearl millet root system growth dynamics, combining stochastic and data-driven modules. The model is capable of simulating the development of observed root phenotypic variability of two millet genotypes chosen for their contrasted root traits. Model description, principle, assumptions, formalism and simulations will be presented during the talk

Glutaredoxin regulation of primary root growth is associated with early drought stress tolerance in pearl millet

Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet’s early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modeling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including genome-wide association study and quantitative trait loci (QTL) approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding gene PgGRXC9 as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homolog AtROXY19 revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment

Glutaredoxin regulation of primary root growth is associated with early drought stress tolerance in pearl millet

Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet’s early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modeling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including genome-wide association study and quantitative trait loci (QTL) approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding gene PgGRXC9 as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homolog AtROXY19 revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment

Author Response: Glutaredoxin regulation of primary root growth is associated with early drought stress tolerance in pearl millet

Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet’s early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modelling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including GWAS and QTL approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding gene PgGRXC9 as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homolog AtROXY19 revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment

Expression of FcRn receptor and pharmacokinetics of monoclonal antibodies

Le FcRn est le récepteur responsable du recyclage des IgG ainsi que de leur transcytose. Ainsi cette protéine a un rôle majeur dans la pharmacocinétique des anticorps thérapeutiques. Nous nous sommes intéressés à différents aspects de l'expression du FcRn. Premièrement nous avons évalué l'influence sur la pharmacocinétique du cétuximab de 2 polymorphismes génétiques influençant l'expression du FcRn. Nous avons montré qu'un Variable Number Tandem Repeat influence la distribution du cétuximab. Nous avons établi que le gène est rarement soumis à des variations de son nombre de copies. Par ailleurs, nous avons montré par une approche de RT-PCR en multiplex l'absence du transcrit FcRn dans les plaquettes humaines. Enfin, l'analyse du niveau de transcrits de FcRn dans un modèle d'activation cellulaire indique qu'il existe une régulation: ce niveau diminue lorsque des monocytes sont différenciés en cellules dendritiques immatures ainsi que lors de l'évolution en cellules dendritiques matures. Les résultats de cette thèse démontrent l'importance de l'étude de l'expression du FcRn dans la variabilité pharmacocinétique des anticorps thérapeutiques.The FcRn is the receptor responsible for the recycling of IgG and their transcytosis. Thus, this protein has a major role in the pharmacokinetics of therapeutic antibodies. We focused on different aspects of FcRn expression. First, we evaluated the influence on the pharmacokinetics of cetuximab of 2 genetic polymorphisms influencing FcRn expression. We showed that a Variable Number Tandem Repeat influences the distribution of the cetuximab. We determined that the gene is rarely affected by Copy Number Variations. Furthermore, we showed by an RT-PCR approach that the FcRn transcript is absent in human platelets. Finally, the analysis of FcRn transcript level in a model of cellular activation indicates that a regulation occurs : the level decreases when monocytes differenciate into immature dendritic cells as well as during evolution into mature dendritic cells. Results of this thesis demonstrate the importance of the study of FcRn expression in pharmokinetic variability of therapeutic antibodies

Influence des polymorphismes du gène FCGRT sur la pharmacocinétique des anticorps thérapeutique

Les anticorps monoclonaux thérapeutiques sont utilisés depuis maintenant plus de 20 ans en médecine. Comme pour tout médicament, il a été montré une forte variabilité pharmacocinétique interindividuelle pouvant influencer leur efficacité. La découverte de marqueurs pharmacogénétiques qui influencent cette variabilité est d un intérêt majeur. Nous avons étudié le gène FCGRT codant la chaîne alpha du FcRn, récepteur impliqué dans la distribution et la protection des anticorps thérapeutiques puisqu il est responsable d une part de leur transcytose et d autre part de leur recyclage. Nous avons évalué l influence de deux polymorphismes de FCGRT sur la pharmacocinétique du cétuximab. Il s agit d une part du Variable Number Tandem Repeat (VNTR) situé au niveau du promoteur et connu pour influencer l expression du FcRn et d autre part de la variation du nombre de copies de FCGRT ou CNV (Copy Number Variation). Ces deux polymorphismes ont été étudiés chez 198 témoins sains et chez 94 patients atteints d un cancer colorectal métastatique traité par cétuximab. Les individus homozygotes pour l allèle VNTR3 présentent une plus faible clairance de distribution du cétuximab que les patients hétérozygotes (VNTR2/VNTR3 et VNTR3/VNTR4) (p=0,021). La clairance d élimination quant à elle n est pas influencée par le génotype VNTR. Concernant les CNV, un seul témoin sain (0,5%) et un seul patient (1,1%) présentent plus de 2 copies de FCGRT, les autres individus en présentent 2. Les paramètres pharmacocinétiques du patient avec plus de 2 copies de FCGRT ne diffèrent pas sensiblement de ceux des patients avec 2 copies. Au total, ces résultats montrent que le VNTR du promoteur de FCGRT influence la pharmacocinétique du cétuximab et que les CNV de FCGRT ne peuvent pas être utilisés en tant que marqueur pharmacogénétique de par leur faible fréquence.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Gota et al. on their article “the pharmacokinetics of Reditux™, a biosimilar of rituximab”

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The neonatal Fc receptor does not modulate hepatitis C virus neutralization

International audienceThe neonatal Fc receptor (FcRn) is the only receptor known to be able to transport IgG across cell barriers and may therefore modulate virus infection. FcRn is expressed efficiently in hepatocytes. We therefore investigated the possible involvement of an FcRn-dependent mechanism in hepatitis C virus (HCV) neutralization. Our study, in both HCV pseudoparticles and HCV in cell-culture models, showed that FcRn was not involved in the intracellular neutralization of HCV, in contrast to the situation observed for influenza A virus

Suggestions to Limit Geometric Distortions in the Reconstruction of Linear Coastal Landforms by SfM Photogrammetry with PhotoScan® and MicMac® for UAV Surveys with Restricted GCPs Pattern

Owing to the combination of technological progress in Unmanned Aerial Vehicles (UAVs) and recent advances in photogrammetry processing with the development of the Structure-from-Motion (SfM) approach, UAV photogrammetry enables the rapid acquisition of high resolution topographic data at low cost. This method is particularly widely used for geomorphological surveys of linear coastal landforms. However, linear surveys are generally pointed out as problematic cases because of geometric distortions creating a “bowl effect” in the computed Digital Elevation Model (DEM). Secondly, the survey of linear coastal landforms is associated with peculiar constraints for Ground Control Points (GCPs) measurements and for the spatial distribution of the tie points. This article aims to assess the extent of the bowl effects affecting the DEM generated above a linear beach with a restricted distribution of GCPs, using different acquisition scenarios and different processing procedures, both with PhotoScan® software tool and MicMac® software tool. It appears that, with a poor distribution of the GCPs, a flight scenario that favors viewing angles diversity can limit DEM’s bowl effect. Moreover, the quality of the resulting DEM also depends on the good match between the flight plan strategy and the software tool via the choice of a relevant camera distortion model

Development and validation of an ELISA to study panitumumab pharmacokinetics

International audiencePanitumumab is a monoclonal antibody directed against EGFR that is approved for the treatment of metastatic colorectal cancer. To investigate its pharmacokinetics and concentration-response relationship, a validated assay is required