Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii

The invasive forms of apicomplexan parasites share a conserved form of gliding motility that powers parasite migration across biological barriers, host cell invasion and egress from infected cells. Previous studies have established that the duration and direction of gliding motility are determined by actin polymerization; however, regulators of actin dynamics in apicomplexans remain poorly characterized. In the absence of a complete ARP2/3 complex, the formin homology 2 domain containing proteins and the accessory protein profilin are presumed to orchestrate actin polymerization during host cell invasion. Here, we have undertaken the biochemical and functional characterization of two Toxoplasma gondii formins and established that they act in concert as actin nucleators during invasion. The importance of TgFRM1 for parasite motility has been assessed by conditional gene disruption. The contribution of each formin individually and jointly was revealed by an approach based upon the expression of dominant mutants with modified FH2 domains impaired in actin binding but still able to dimerize with their respective endogenous formin. These mutated FH2 domains were fused to the ligand-controlled destabilization domain (DD-FKBP) to achieve conditional expression. This strategy proved unique in identifying the non-redundant and critical roles of both formins in invasion. These findings provide new insights into how controlled actin polymerization drives the directional movement required for productive penetration of parasites into host cells

vulnerabilités et capabilités

Collectif dirige par mylene baum sur le lien entre vulnerabilités clinique et caapbilisations de patient

A patient-administered medical risk related history questionnaire (EMRRH) for use in 10 European countries (multicenter trial)

Objective. The objective of this study was to produce a standardized medical risk-related history (MRRH) in order to identify the medically compromised patient (MCP) attending the general dental practitioner for treatment, to develop such a history (EMRRH), and to validate it in dental practices in 10 European countries. Study design. The Dutch MRRH, adapted to allow for legal and cultural differences of the participating countries was introduced. After consensus and repeated testing, the questionnaire was validated. In this last phase, 1000 patients older than 18 attending dental practices were selected, 100 per country; 994 medical histories were suitable for statistical analysis. Validation was carried out by a physician accustomed to making preoperative assessments, including the ASA risk classification. Results. Mean specificity per country was 99.1 and per EMRRH item was 99.0. Mean sensitivity per country was 93.2 and per item was 93.7. Cohen's kappa for the countries involved was 0.81 to 0.98 and for subsequent questions was 0.81 to 0.97. Conclusion. The EMRRH was found to be valid in the detection of medically compromised patients in 10 European countrie

Allele diversity at orthologous candidate genes in GCP crops (ADOC project)

International audienc