In vivo labelling of resting monocytes in the reticuloendothelial system with fluorescent iron oxide nanoparticles prior to injury reveals that they are mobilized to infarcted myocardium

Aims To evaluate the feasibility of loading resting monocytes/macrophages by intravenous (i.v.) injection of fluorescent iron oxide nanoparticles prior to injury and tracking of these cells in the very same animal to myocardial infarction (MI) by magnetic resonance imaging (MRI) and optical imaging. Methods and results Rats were injected with fluorescent iron oxide nanoparticles (10 mg/kg) (n = 15) prior to injury. After disappearance of the nanoparticles from the blood, MI was induced. Monocytes/macrophages were then tracked in the very same animal by MRI and optical imaging. Control groups were (i) non-injected animals (n = 15), (ii) injected animals associated with a sham operation (n = 8), and (iii) animals treated with an anti-inflammatory agent (n = 6). The presence of iron-loaded cells can be detected by MRI in vivo in the infarcted myocardium. Here, we showed that the detection of inflammatory cells in vivo correlated well with ex vivo imaging (MRI and reflectance fluorescence) and histology. We also showed that the method is robust enough to depict changes in the inflammatory response. Conclusion This study demonstrates that resting monocytes/macrophages can be loaded in vivo by a simple i.v. injection of fluorescent superparamagnetic iron oxide nanoparticles prior to injury and then tracked, in the same animal, in a model of ischaemia-reperfusion leading to myocardial infarct. Although previous studies of macrophages infiltration following MI have labelled the macrophages after injury, this study, for the first time, has pre-load the resting monocytes with fluorescent iron oxide nanoparticle

Carbohydrates in plant immunity and plant protection: roles and potential application as foliar sprays

Increasing interest is devoted to carbohydrates for their roles in plant immunity. Some of them are elicitors of plant defenses whereas other ones act as signaling molecules in a manner similar to phytohormones. This review first describes the main classes of carbohydrates associated to plant immunity, their role and mode of action. More precisely, the state of the art about perception of “PAMP, MAMP and DAMP type” oligosaccharides is presented and examples of induced defense events are provided. A particular attention is paid to the structure / activity relationships of these compounds. The role of sugars as signaling molecules, especially in plant microbe interactions, is also presented. Secondly, the potentialities and limits of foliar sprays of carbohydrates to stimulate plant immunity for crop protection against diseases are discussed, with focus on the roles of the leaf cuticle and phyllosphere microflora.Peer reviewe

Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome

Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a “second hit,” that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome

IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype

Background: Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies. Methods: We screened 1628 individuals with reno-ocular ciliopathies by targeted next-generation sequencing of ciliary candidate genes, including all IFT-B encoding genes. Results: Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling. Conclusions: This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development

Induction de résistance des plantes : état des lieux

National audienc

Biocontrôle en viticulture

National audienc

Mode d'action des SDP - Un point sur les phosphonates

National audienc

Chemical inducers of resistance in plants

International audienceResistance of plants towards potential pathogens is regulated by a variety of different local or systemic defence mechanisms which are either constitutively active or inducible upon challenge with a pathogen. Based on the knowledge acquired in studies on the molecular and biochemical mechanisms underlying especially different natural induced resistance phenomena, chemical inducers of resistance, derived both from plants or microorganisms or generated synthetically have been characterised and used to improve plant health. This article gives an overview on the present knowledge on resistance inducers and points to possible applications in the future

Chemical inducers of resistance in plants

International audienceResistance of plants towards potential pathogens is regulated by a variety of different local or systemic defence mechanisms which are either constitutively active or inducible upon challenge with a pathogen. Based on the knowledge acquired in studies on the molecular and biochemical mechanisms underlying especially different natural induced resistance phenomena, chemical inducers of resistance, derived both from plants or microorganisms or generated synthetically have been characterised and used to improve plant health. This article gives an overview on the present knowledge on resistance inducers and points to possible applications in the future