Analyse des données d'expression de gènes

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Role of the extracellular matrix proteins in the resistance of SP6.5 uveal melanoma cells toward cisplatin

Uveal melanoma is the most frequent primary intraocular tumor in the adult population. This malignancy has a high mortality rate and responds poorly to existing chemotherapy. Recently, the tumor environment has been found to exert a profound influence on drug response through cell interaction with components from the extracellular matrix (ECM). In the present study, we investigated whether individual components from the ECM may affect cell survival and/or cell death induced by the cytotoxic agent cisplatin on the SP6.5 uveal melanoma cell line. Tumor cells were shown by immunofluorescence analyses to be surrounded by the ECM proteins fibronectin (FN), type IV collagen (CIV) and laminin (LM), both at the primary and metastatic sites. Binding of SP6.5 cells to FN, LM and CIV is primarily dictated by the expression of membrane bound integrins from the beta1 family as revealed by cell adhesion assays conducted on ECM-coated culture plates. Analysis of cell death by flow cytometry demonstrated that culturing SP6.5 cells in the presence of FN, CIV and LM, substantially reduced the percentage of cells undergoing apoptosis after cisplatin treatment when compared with those seeded on a non-permissive matrix. These results suggest that adhesion of the SP6.5 uveal melanoma cells to the ECM proteins FN, CIV and LM might therefore confer resistance to the chemotherapeutic agent cisplatin. The cellular resistance induced by the ECM proteins toward cisplatin could explain in part the local recurrence of metastasis derived from uveal melanoma often observed clinically after chemotherapy

Développement d’un insecte artificiel. Nanodrone dédié à la surveillance intra-bâtiment

Dans l’optique de réaliser de la surveillance intra-bâtiment avec un système autonome, mobile, très discret, des recherches sont en cours pour développer des nanodrones. Elles se concentrent sur la compréhension et l’imitation du vol battu des insectes et sur les aspects de la miniaturisation. Cet article décrit la conception et la réalisation d’un insecte artificiel à ailes résonantes à l’aide des technologies de microfabrication de la microélectronique. Un actionneur électromagnétique induit un mouvement de flexion/torsion des ailes correspondant à une cinématique similaire à celle des insectes. L’estimation des phénomènes aéroélastiques en grands déplacements est réalisée à l’aide d’un modèle basé sur les éléments finis et une formulation analytique de l’aérodynamique. Une validation expérimentale est ensuite proposée

Redirecting splicing with bifunctional oligonucleotides

Abstract: Ectopic modulators of alternative splicing are important tools to study the function of splice variants and for correcting mis-splicing events that cause human diseases. Such modulators can be bifunctional oligonucleotides made of an antisense portion that determines target specificity, and a nonhybridizing tail that recruits proteins or RNA/protein complexes that affect splice site selection (TOSS and TOES, respectively, for targeted oligonucleotide silencer of splicing and targeted oligonucleotide enhancer of splicing). The use of TOSS and TOES has been restricted to a handful of targets. To generalize the applicability and demonstrate the robustness of TOSS, we have tested this approach on more than 50 alternative splicing events. Moreover, we have developed an algorithm that can design active TOSS with a success rate of 80%. To produce bifunctional oligonucleotides capable of stimulating splicing, we built on the observation that binding sites for TDP-43 can stimulate splicing and improve U1 snRNP binding when inserted downstream from 50 splice sites. A TOES designed to recruit TDP-43 improved exon 7 inclusion in SMN2. Overall, our study shows that bifunctional oligonucleotides can redirect splicing on a variety of genes, justifying their inclusion in the molecular arsenal that aims to alter the production of splice variants

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (N = 25) and two (N = 25) and four (N = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (Kglc) declined by 6%–12% mainly in the temporo-parietal lobes and cingulate gyri (p ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions (p ≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. Kglc in the caudate was directly related to performance on several cognitive tests (r = +0.41 to +0.43, allp ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to Kglc in the thalamus (r = −0.44, p = 0.04) and in the caudate (r = −0.43, p = 0.05), and also inversely related to executive function, attention and processing speed (r = −0.45 to −0.53, all p ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in Kglc is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac

Initial results from a hydroacoustic network to monitor submarine lava flows near Mayotte Island

In 2019, a new underwater volcano was discovered at 3500 m below sea level (b.s.l.), 50 km east of Mayotte Island in the northern part of the Mozambique Channel. In January 2021, the submarine eruption was still going on and the volcanic activity, along with the intense seismicity that accompanies this crisis, was monitored by the recently created REVOSIMA (MAyotte VOlcano and Seismic Monitoring) network. In this framework, four hydrophones were moored in the SOFAR channel in October 2020. Surrounding the volcano, they monitor sounds generated by the volcanic activity and the lava flows. The first year of hydroacoustic data evidenced many earthquakes, underwater landslides, large marine mammal calls, along with anthropogenic noise. Of particular interest are impulsive signals that we relate to steam bursts during lava flow emplacement. A preliminary analysis of these impulsive signals (ten days in a year, and only one day in full detail) reveals that lava emplacement was active when our monitoring started, but faded out during the first year of the experiment. A systematic and robust detection of these specific signals would hence contribute to monitor active submarine eruptions in the absence of seafloor deep-tow imaging or swath-bathymetry surveys of the active area

Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

International audienceABSTRACT: BACKGROUND: Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. METHODS: Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. RESULTS: Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT29 and SW620 express higher levels of a splice variant of DR3 that has no trans-membrane domain and no death domain. CONCLUSION: Colon cancer cells acquire an increased capacity to survive via the activation of the PI3K/NFκB pathway following the stimulation of DR3 by E-selectin. Generation of a DR3 splice variant devoid of death domain can further contribute to protect against apoptosis

La révolution Internet et la résistance virtuelle : Le cas zapatiste

Au milieu des années 1990, alors qu’internet commençait à peine à être connu du plus grand nombre, le sous-commandant Marcos entreprenait de diffuser, par le biais de listes électroniques et de sites Web, des communiqués relatifs à la résistance zapatiste. Lentement mais sûrement, le premier mouvement global de résistance virtuelle prenait racine. En replaçant les revendications autochtones dans le cadre plus général de la critique du néolibéralisme et de l’affirmation des principes universels de la démocratie, de la liberté et de la justice, les zapatistes ont élaboré un discours de portée globale qui leur a permis de rejoindre la sensibilité d’un nombre impressionnant d’internautes provenant de tous les coins de la planète. Toutefois, en jouant simultanément sur les registres local et global, les zapatistes risquent de s’éloigner de la réalité autochtone et de voir leurs actions et leur projet politique de plus en plus figés. Finalement, l’ampleur de la solidarité virtuellement exprimée permet d’avancer l’hypothèse de l’émergence d’un nouveau contrat social global par l’entremise du Web.With the rise of the Internet’s popularity in the mid-1990s, Subcommandant Marcos, using electronic mailing lists and websites, began to disseminate information about the Zapatista resistance movement. Slowly but surely, the first virtual global resistance movement began to take root. By resituating native rights claims within the general framework of neoliberal criticism and affirmations of universal principles of democracy, liberty and justice, the Zapatistas have developed a global discourse which has enabled them to reach an impressive number of Internet users ail over the world. However, by playing both the local and global angles, Zapatistas are in danger of distancing themselves from native reality, and losing the original focus of their movement. Finally, the breadth of virtual solidarity for this movement makes it possible to advance the theory of the emergence of a new global social contract through the Internet