Le Fonds d'investissement de Montréal

monographi

La Coopérative d’habitation des Cantons de l’Est

Recherche réalisée grâce aux contributions de la Chaire de coopération Guy-Bernier et du Conseil de recherches en sciences humaines du Canada

A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury.

The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner. Here we report that EVT901 reduces binding of pro-nerve growth factor to p75 neurotrophin receptor, blocks pro-nerve growth factor induced apoptosis in cells expressing p75 neurotrophin receptor, and enhances neurite outgrowth in vitro Furthermore, we demonstrate that EVT901 abrogates p75 neurotrophin receptor signalling by other ligands, such as prion peptide and amyloid-β. To test the efficacy of EVT901 in vivo, we evaluated the outcome in two models of traumatic brain injury. We generated controlled cortical impacts in adult rats. Using unbiased stereological analysis, we found that EVT901 delivered intravenously daily for 1 week after injury, reduced lesion size, protected cortical neurons and oligodendrocytes, and had a positive effect on neurological function. After lateral fluid percussion injury in adult rats, oral treatment with EVT901 reduced neuronal death in the hippocampus and thalamus, reduced long-term cognitive deficits, and reduced the occurrence of post-traumatic seizure activity. Together, these studies provide a new reagent for altering p75 neurotrophin receptor actions after injury and suggest that EVT901 may be useful in treatment of central nervous system trauma and other neurological disorders where p75 neurotrophin receptor signalling is affected

Antimicrobial resistance in outpatient Escherichia coli urinary isolates in Dakar, Senegal.

International audienceBACKGROUND: Data regarding the evolution of antimicrobial resistance are needed to suggest appropriate empirical treatment of urinary tract infections (UTI) in developing countries. To assess the antimicrobial susceptibility of Escherichia coli, the predominant pathogen in community-acquired UTI, a prospective multicenter study was carried out in Dakar, Senegal. METHODOLOGY: From February 2004 to October 2006, 1010 non-duplicate E. coli strains were collected from four centres. Antimicrobial susceptibility testing was performed using disk diffusion method according to the recommendations of the CA-SFM (2004). RESULTS: Most of the isolates were resistant to amoxicillin (73.1%), amoxicillin-clavulanic acid (67.5%), cephalothin (55.8%), and trimethoprim/sulfamethoxazole (68.1%). Extended spectrum beta-lactamase was detected in 38 strains. The overall resistance rates to nalidixic acid, norfloxacin and ciprofloxacin were 23.9%, 16.4% and 15.5%, respectively. Most of the strains were susceptible to gentamicin, nitrofurantoin and fosfomycin (respective susceptibility rates, 93.8%, 89.9%, and 99.3%). During this period, a significant decrease in sensitivity was observed for cephalothin, fluoroquinolones and trimethoprim/sulfamethoxazole (p<0.001). CONCLUSIONS: These data suggest that trimethoprim/sulfamethoxazole may no longer be used as empirical treatment for community-acquired UTI in Dakar. In order to preserve the activity of fluoroquinolones for future years, alternatives such as fosfomycin or nitrofurantoin should be considered

Patterns of sequence polymorphism in the fleshless berry locus in cultivated and wild Vitis vinifera accessions

<p>Abstract</p> <p>Background</p> <p>Unlike in tomato, little is known about the genetic and molecular control of fleshy fruit development of perennial fruit trees like grapevine (<it>Vitis vinifera </it>L.). Here we present the study of the sequence polymorphism in a 1 Mb grapevine genome region at the top of chromosome 18 carrying the <it>fleshless berry </it>mutation (<it>flb</it>) in order, first to identify SNP markers closely linked to the gene and second to search for possible signatures of domestication.</p> <p>Results</p> <p>In total, 62 regions (17 SSR, 3 SNP, 1 CAPS and 41 re-sequenced gene fragments) were scanned for polymorphism along a 3.4 Mb interval (85,127-3,506,060 bp) at the top of the chromosome 18, in both <it>V. vinifera cv</it>. Chardonnay and a genotype carrying the <it>flb </it>mutation, <it>V. vinifera cv</it>. Ugni Blanc mutant. A nearly complete homozygosity in Ugni Blanc (wild and mutant forms) and an expected high level of heterozygosity in Chardonnay were revealed. Experiments using qPCR and BAC FISH confirmed the observed homozygosity. Under the assumption that <it>flb </it>could be one of the genes involved into the domestication syndrome of grapevine, we sequenced 69 gene fragments, spread over the <it>flb </it>region, representing 48,874 bp in a highly diverse set of cultivated and wild <it>V. vinifera </it>genotypes, to identify possible signatures of domestication in the cultivated <it>V. vinifera </it>compartment. We identified eight gene fragments presenting a significant deviation from neutrality of the Tajima's D parameter in the cultivated pool. One of these also showed higher nucleotide diversity in the wild compartments than in the cultivated compartments. In addition, SNPs significantly associated to berry weight variation were identified in the <it>flb </it>region.</p> <p>Conclusions</p> <p>We observed the occurrence of a large homozygous region in a non-repetitive region of the grapevine otherwise highly-heterozygous genome and propose a hypothesis for its formation. We demonstrated the feasibility to apply BAC FISH on the very small grapevine chromosomes and provided a specific probe for the identification of chromosome 18 on a cytogenetic map. We evidenced genes showing putative signatures of selection and SNPs significantly associated with berry weight variation in the <it>flb </it>region. In addition, we provided to the community 554 SNPs at the top of chromosome 18 for the development of a genotyping chip for future fine mapping of the <it>flb </it>gene in a F2 population when available.</p

DC Grids : Motivation, Feasibility and Outstanding Issues : Status Report for the European Commission Deliverable : D5.4

Wind energy is already a mainstay of clean power generation in Europe, with over 100GW of capacity installed so far, and another 120GW anticipated by 2020 according to various analysts. Much of this capacity is expected to be installed offshore, as it is a windier and the source is steadier compared to onshore wind energy. Hence, offshore wind has been envisaged as making a critical contribution to Europe’s demand for electrical energy and to minimising the carbon emissions associated with meeting that demand

Trueness and precision of the real-time RT-PCR method for quantifying the chronic bee paralysis virus genome in bee homogenates evaluated by a comparative inter-laboratory study

The Chronic bee paralysis virus (CBPV) is the aetiological agent of chronic bee paralysis, a contagious disease associated with nervous disorders in adult honeybees leading to massive mortalities in front of the hives. Some of the clinical signs frequently reported, such as trembling, may be confused with intoxication syndromes. Therefore, laboratory diagnosis using real-time PCR to quantify CBPV loads is used to confirm disease. Clinical signs of chronic paralysis are usually associated with viral loads higher than 108 copies of CBPV genome copies per bee (8 log(10) CBPV/bee). This threshold is used by the European Union Reference Laboratory for Bee Health to diagnose the disease. In 2015, the accuracy of measurements of three CBPV loads (5, 8 and 9 log(10) CBPV/bee) was assessed through an inter-laboratory study. Twenty-one participants, including 16 European National Reference Laboratories, received 13 homogenates of CBPV-infected bees adjusted to the three loads. Participants were requested to use the method usually employed for routine diagnosis. The quantitative results (n = 270) were analysed according to international standards NF ISO 13528 (2015) and NF ISO 5725-2 (1994). The standard deviations of measurement reproducibility (S-R) were 0.83, 1.06 and 1.16 at viral loads 5, 8 and 9 log(10) CBPV/bee, respectively. The inter-laboratory confidence of viral quantification (+/- 1.96 S-R) at the diagnostic threshold (8 log(10) CBPV/bee) was +/- 2.08 log(10) CBPV/bee. These results highlight the need to take into account the confidence of measurements in epidemiological studies using results from different laboratories. Considering this confidence, viral loads over 6 log(10) CBPV/bee may be considered to indicate probable cases of chronic paralysis