Caractérisation d'une protéine humaine potentiellement impliquée dans l'infection par Toxoplasma gondii

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Spire-1 contributes to the invadosome and its associated invasive properties.

International audienceCancer cells have an increased ability to squeeze through extracellular matrix gaps that they create by promoting proteolysis of its components. Major sites of degradation are specialized micro-domains in the plasma membrane collectively named invadosomes where the Arp2/3 complex and formin proteins cooperate to spatio-temporally control actin nucleation and the folding of a dynamic F-actin core. At invadosomes, proper coupling of exo-endocytosis allows polarized delivery of proteases that facilitate degradation of ECM and disruption of the cellular barrier. We investigated the contribution of the actin nucleator Spire-1 to invadosome structure and function, using Src-activated cells and cancer cells. We found that Spire-1 is specifically recruited at invadosomes and is part of a multi-molecular complex containing Src kinase, the formin mDia1 and actin. Spire-1 interacts with the Rab3A GTPase, a key player in the regulation of exocytosis that is present at invadosomes. Finally, over- and under-expression of Spire-1 resulted in cells with an increased or decreased potential for matrix degradation, respectively, therefore suggesting a functional interplay of Spire-1 with both actin nucleation and vesicular trafficking that might impact on cell invasive and metastatic behavior

A Toxoplasma type 2C serine-threonine phosphatase is involved in parasite growth in the mammalian host cell.

International audienceToxoplasma gondii is a human protozoan parasite that belongs to the phylum of Apicomplexa and causes toxoplasmosis. As the other members of this phylum, T. gondii obligatory multiplies within a host cell by a peculiar type of mitosis that leads to daughter cell assembly within a mother cell. Although parasite growth and virulence have been linked for years, few molecules controlling mitosis have been yet identified and they include a couple of kinases but not the counteracting phosphatases. Here, we report that in contrast to other animal cells, type 2C is by far the major type of serine threonine phosphatase activity both in extracellular and in intracellular dividing parasites. Using wild type and transgenic parasites, we characterized the 37kDa TgPP2C molecule as an abundant cytoplasmic and nuclear enzyme with activity being under tight regulation. In addition, we showed that the increase in TgPP2C activity significantly affected parasite growth by impairing cytokinesis while nuclear division still occurred. This study supports for the first time that type 2C protein phosphatase is an important regulator of cell growth in T. gondii

Mortality and disability according to baseline blood pressure in acute ischemic stroke patients treated by thrombectomy: a collaborative pooled analysis

International audienceHigh blood pressure (BP) is associated with worse clinical outcomes in the setting of acute ischemic stroke, but the optimal blood pressure target is still a matter of debate. We aimed to study the association between baseline BP and mortality in acute ischemic stroke patients treated by mechanical thrombectomy.A total of 1332 acute ischemic stroke patients treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016) in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Linear and polynomial logistic regression models were used to assess the association between BP and mortality and functional outcome at 90 days. Highest mortality was found at lower and higher baseline systolic blood pressure (SBP) values following a J- or U-shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143-170). When SBP values were categorized in 10-mm Hg increments, the odds ratio for all-cause mortality was 3.78 (95% confidence interval 1.50-9.55) for SBP<110 mm Hg and 1.81 (95% confidence interval 1.01-3.36) for SBP≥180 mm Hg using SBP≥150 to 160 mm Hg as reference. The rate of favorable outcome was the highest at low SBP values and lowest at high SBP values, with a nonlinear relationship; in unplanned exploratory analysis, an optimal threshold SBP≥177 mm Hg was found to predict unfavorable outcome (adjusted odds ratio 0.47; 95% confidence interval 0.31-0.70).In acute ischemic stroke patients treated by mechanical thrombectomy, baseline SBP is associated with all-cause mortality and favorable outcome. In contrast to mortality, favorable outcome rate was the highest at low SBP values and lowest at high SBP values. Further studies are warranted to confirm these findings

Silent Cerebral Small-Vessel Disease Is Twice as Prevalent in Middle-Aged Individuals With Well-Controlled, Combination Antiretroviral Therapy–Treated Human Immunodeficiency Virus (HIV) Than in HIV-Uninfected Individuals

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Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy

International audienceBackground and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results—In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography–based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions—The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design