Régulation intracellulaire du VEGFR-2 menant à l'activation d'eNOS dans les cellules endothéliales

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Pharmacologie des nucléotides extracellulaires et de la NTPDase au niveau des circuits mésentériques pré et postcapillaires de cobaye

La présente étude avait comme buts principaux de déterminer l'action vasoactive de l'ATP, de l'ADP et de l'AMP au niveau de la vascularisation mésentérique pré et postcapillaires de cobaye, ainsi que de vérifier la modulation de cet effet par l'endothélium. L'ATP est rapidement métabolisé en adénosine par l'action de deux enzymes soient, la nucléoside triphosphate diphosphohydrolase (NTPDase) et la 5 '-nucléotidase. Nous nous sommes particulièrement intéressés à la NTPDase qui hydrolyse de façon séquentielle les liens [delta] et [bêta] des groupements phosphates de l'ATP. Nos résultats ont démontré que les nucléotides étudiés ont un effet relaxant tant au niveau de la vascularisation précapillaire que postcapillaire. Cependant, cet effet était beaucoup plus faible du côté veineux. Nous avons également identifié que l'effet relaxant induit par l'ATP, l'ADP et l'AMP extracellulaires, était dépendant de l'endothélium. Nos résultats suggèrent l'implication de la prostacycline, de l'oxyde nitrique et de l'EDHF dans le mécanisme de vasodilatation induit par ces purines. Par chromatographie en phase liquide à haute performance nous avons mis en évidence la présence et l'efficacité d'une NTPDase au niveau de la vascularisation mésentérique artérielle et veineuse de cobaye. Nos résultats suggèrent que les circuits vasculaires précapillaires et postcapillaires sont impliqués de façon qualitativement différentes dans le métabolisme de l'ATP. Nos résultats démontrent aussi un rôle significatif de l'endothélium et de la NTPDase dans la production d'ADP et d'AMP suite à l'administration exogène d'ATP

The Effects of Physical Activity in Parkinson’s Disease: A Review

Background: Physical activity (PA) is increasingly advocated as an adjunct intervention for individuals with Parkinson’s disease (PD). However, the specific benefits of PA on the wide variety of impairments observed in patients with PD has yet to be clearly identified. Objective: Highlight health parameters that are most likely to improve as a result of PA interventions in patients with PD. Methods: We compiled results obtained from studies examining a PA intervention in patients with PD and who provided statistical analyses of their results. 868 outcome measures were extracted from 106 papers published from 1981 to 2015. The results were classified as having a statistically significant positive effect or no effect. Then, outcome measures were grouped into four main categories and further divided into sub-categories. Results: Our review shows that PA seems most effective in improving Physical capacities and Physical and cognitive functional capacities. On the other hand, PA seems less efficient at improving Clinical symptoms of PD and Psychosocial aspects of life, with only 50% or less of results reporting positive effects. The impact of PA on Cognitive functions and Depression also appears weaker, but few studies have examined these outcomes. Discussion: Our results indicate that PA interventions have a positive impact on physical capacities and functional capacities. However, the effect of PA on symptoms of the disease and psychosocial aspects of life are moderate and show more variability. This review also highlights the need for more research on the effects of PA on cognitive functions, depression as well as specific symptoms of PD

Ubiquitous Hepatocystis infections, but no evidence of Plasmodium falciparum-like malaria parasites in wild greater spot-nosed monkeys (Cercopithecus nictitans)

Western gorillas (Gorilla gorilla) have been identified as the natural reservoir of the parasites that were the immediate precursor of Plasmodium falciparum infecting humans. Recently, a P. falciparum-like sequence was reported in a sample from a captive greater spot-nosed monkey (Cercopithecus nictitans), and was taken to indicate that this species may also be a natural reservoir for P. falciparum-related parasites. To test this hypothesis we screened blood samples from 292 wild C nictitans monkeys that had been hunted for bushmeat in Cameroon. We detected Hepatocystis spp. in 49% of the samples, as well as one sequence from a clade of Plasmodium spp. previously found in birds, lizards and bats. However, none of the 292 wild C. nictitans harbored P. falciparum-like parasites

Identification of precursor transcripts for 6 novel miRNAs expands the diversity on the genomic organisation and expression of miRNA genes in rice

<p>Abstract</p> <p>Background</p> <p>The plant miRNAs represent an important class of endogenous small RNAs that guide cleavage of an mRNA target or repress its translation to control development and adaptation to stresses. MiRNAs are nuclear-encoded genes transcribed by RNA polymerase II, producing a primary precursor that is subsequently processed by DCL1 an RNase III Dicer-like protein.</p> <p>In rice hundreds of miRNAs have been described or predicted, but little is known on their genes and precursors which are important criteria to distinguish them from siRNAs. Here we develop a combination of experimental approaches to detect novel miRNAs in rice, identify their precursor transcripts and genes and predict or validate their mRNA targets.</p> <p>Results</p> <p>We produced four cDNA libraries from small RNA fractions extracted from distinct rice tissues. By <it>in silico </it>analysis we selected 6 potential novel miRNAs, and confirmed that their expression requires OsDCL1. We predicted their targets and used 5'RACE to validate cleavage for three of them, targeting a PPR, an SPX domain protein and a GT-like transcription factor respectively.</p> <p>In addition, we identified precursor transcripts for the 6 miRNAs expressed in rice, showing that these precursors can be efficiently processed using a transient expression assay in transfected <it>Nicotiana benthamiana </it>leaves. Most interestingly, we describe two precursors producing tandem miRNAs, but in distinct arrays. We focus on one of them encoding osa-miR159a.2, a novel miRNA produced from the same stem-loop structure encoding the conserved osa-miR159a.1. We show that this dual osa-miR159a.2-osa-miR159a.1 structure is conserved in distant rice species and maize. Finally we show that the predicted mRNA target of osa-miR159a.2 encoding a GT-like transcription factor is cleaved <it>in vivo </it>at the expected site.</p> <p>Conclusion</p> <p>The combination of approaches developed here identified six novel miRNAs expressed in rice which can be clearly distinguished from siRNAs. Importantly, we show that two miRNAs can be produced from a single precursor, either from tandem stem-loops or tandemly arrayed in a single stem-loop. This suggests that processing of these precursors could be an important regulatory step to produce one or more functional miRNAs in plants and perhaps coordinate cleavage of distinct targets in the same plant tissue.</p

Chromosomal Instability in Near-Diploid Colorectal Cancer: A Link between Numbers and Structure

Chromosomal instability (CIN) plays a crucial role in tumor development and occurs mainly as the consequence of either missegregation of normal chromosomes (MSG) or structural rearrangement (SR). However, little is known about the respective chromosomal targets of MSG and SR and the way these processes combined within tumors to generate CIN. To address these questions, we karyotyped a consecutive series of 96 near-diploid colorectal cancers (CRCs) and distinguished chromosomal changes generated by either MSG or SR in tumor cells. Eighty-three tumors (86%) presented with chromosomal abnormalities that contained both MSGs and SRs to varying degrees whereas all 13 others (14%) showed normal karyotype. Using a maximum likelihood statistical method, chromosomes affected by MSG or SR and likely to represent changes that are selected for during tumor progression were found to be different and mostly mutually exclusive. MSGs and SRs were not randomly associated within tumors, delineating two major pathways of chromosome alterations that consisted of either chromosome gains by MSG or chromosomal losses by both MSG and SR. CRCs showing microsatellite instability (MSI) presented with either normal karyotype or chromosome gains whereas MSS (microsatellite stable) CRCs exhibited a combination of the two pathways. Taken together, these data provide new insights into the respective involvement of MSG and SR in near-diploid colorectal cancers, showing how these processes target distinct portions of the genome and result in specific patterns of chromosomal changes according to MSI status