16 research outputs found

    ERK1 as a therapeutic target for dendritic cell vaccination against high-grade gliomas

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    Glioma regression requires the recruitment of potent anti-tumor immune cells into the tumor microenvironment. Dendritic cells (DCs) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified especially to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the present study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence

    Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction

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    OBJECTIVE: OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients. METHODS: Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. RESULTS: Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. CONCLUSIONS: Our results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration

    Coral aquaculture: applying scientific knowledge to ex situ production

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    Coral aquaculture is an activity of growing interest due to the degradation of coral reefs worldwide and concomitant growing demand for corals by three industries: marine ornamental trade, pharmaceutical industry and reef restoration. Although captive breeding and propagation of corals is a well-known activity among aquarium hobbyists and public aquariums, the link between coral science and aquaculture is still poorly developed. Research on coral biology has increased in the past decades and resulted in abundant scientific information that is pivotal to further advance coral aquaculture. This review presents a holistic overview of coral aquaculture in relation to coral biology, with particular focus on ex situ aquaculture. Success factors for commercial coral aquaculture are outlined, which include qualitative aspects, such as shape, coloration and natural product content, and quantitative parameters such as growth and volumetric productivity. Manipulation of environmental factors to maximize coral quality and volumetric productivity is thoroughly discussed, and a comprehensive overview of current propagation techniques is provided. Knowledge gaps are pinpointed to indicate directions for future research

    Percolation-based vibrational picture to estimate nonrandom N substitution in GaAsN alloys

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    International audienceThe number of N atoms in N-rich regions mostly due to nonrandom N incorporation in GaAsN (N∼4%), referred to as the Nr rate, is studied using a nonstandard Raman setup that addresses transverse symmetry. The Ga-N opticalrange shows a two-mode signal which discriminates between the N-poor ( Np ) and N-rich (Nr) regions. This is discussed via a percolation-based picture for Be-chalcogenide alloys, which exhibit mechanical contrast with regard to the shear modulus. This applies to GaAs-GaN even though the contrast is in the bulk modulus. The balance of Nr/Np strength provides a Nr rate of ∼30%, i.e., much larger than the corresponding Be rate of ∼4% in random Be-based alloys

    Investigation of a leptospirosis outbreak in triathlon participants, Réunion Island, 2013

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    We report herein the investigation of a leptospirosis outbreak occurring in triathlon competitors on Réunion Island, Indian Ocean. All participants were contacted by phone or email and answered a questionnaire. Detection and molecular characterization of pathogenic Leptospira was conducted in inpatients and in rodents trapped at the vicinity of the event. Of the 160 athletes competing, 101 (63·1%) agreed to participate in the study. Leptospirosis was biologically confirmed for 9/10 suspected cases either by real-time PCR or serological tests (MAT or ELISA). The total attack rate, children's attack rate, swimmers' attack rate, and the attack rate in adult swimmers were respectively estimated at 8·1% [95% confidence interval (CI) 4·3–14·7], 0%, 12·7% (95% CI 6·8–22·4) and 23·1% (95% CI 12·6–33·8). Leptospirosis cases reported significantly more wounds [risk ratio (RR) 4·5, 95% CI 1·6–13], wore complete neoprene suits less often (RR 4·3, 95% CI 1·3–14·5) and were most frequently unlicensed (RR 6·6, 95% CI 2·9–14·8). The epidemiological investigation supported that some measures such as the use of neoprene suits proved efficient in protecting swimmers against infection. PCR detection in rats revealed high Leptospira infection rates. Partial sequencing of the 16S gene and serology on both human and animal samples strongly suggests that rats were the main contaminators and were likely at the origin of the infection in humans
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