Modulation of I����/I�� by cellular metabolites : implication in the arrhythmogenesis during myocardial ischemia

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

Fatty acid metabolism and modulation of human breast cancer cell survival

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

Neuroprotection and regeneration of adult lesioned retinal ganglion cells by the modulation of fibroblast growth factor-2 and receptor tyrosine phosphatase-sigma

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

Modulation of the actin cytoskeleton in the folliculo-stellate cell line TtT/GF by serum factors

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

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.

Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene

Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -ε isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -ε activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process.

Mucosal modulation of contractility in bladder strips from normal and overactive rat models and the effect of botulinum toxin A on overactive bladder strips

AIMS: To investigate the local, regulatory role of the mucosa on bladder strip contractility from normal and overactive bladders and to examine the effect of botulinum toxin A (BoNT-A).

METHODS: Bladder strips from spontaneously hyperactive rat (SHR) or normal rats (Sprague Dawley, SD) were dissected for myography as intact or mucosa-free preparations. Spontaneous, neurogenic and agonist-evoked contractions were investigated. SHR strips were incubated in BoNT-A (3 h) to assess effects on contractility.

RESULTS: Spontaneous contraction amplitude, force-integral or frequency were not significantly different in SHR mucosa-free strips compared with intacts. In contrast, spontaneous contraction amplitude and force-integral were smaller in SD mucosa-free strips than in intacts; frequency was not affected by the mucosa. Frequency of spontaneous contractions in SHR strips was significantly greater than in SD strips. Neurogenic contractions in mucosa-free SHR and SD strips at higher frequencies were smaller than in intact strips. The mucosa did not affect carbachol-evoked contractions in intact versus mucosa-free strips from SHR or SD bladders. BoNT-A reduced spontaneous contractions in SHR intact strips; this trend was also observed in mucosa-free strips but was not significant. Neurogenic and carbachol-evoked contractions were reduced by BoNT-A in mucosa-free but not intact strips. Depolarisation-induced contractions were smaller in BoNT-A-treated mucosa-free strips.

CONCLUSIONS: The mucosal layer positively modulates spontaneous contractions in strips from normal SD but not overactive SHR bladder strips. The novel finding of BoNT-A reduction of contractions in SHR mucosa-free strips indicates actions on the detrusor, independent of its classical action on neuronal SNARE complexes.

Role and modulation of maternal transcripts during the first cleavage divisions in bovine embryos

Ce travail porte sur l’identification, la fonction et la régulation des molécules maternelles d’ARNm qui dirigent la compétence développementale juste après la fécondation chez les bovins. Tout d’abord, en utilisant le modèle du temps écoulé jusqu’au premier clivage zygotique et à travers l’évaluation du transcriptome des embryons à 2-cellules, il fut possible de déterminer la signature moléculaire des niveaux extrêmes de compétence au développement et sélectionner des molécules candidates pour des études postérieures. Les résultats ont montré que les embryons de capacité développementale variable diffèrent dans certaines fonctions comme la réparation de l’ADN, le traitement de l’ARN, la synthèse de protéines et l’expression génique définies par des ARNm synthétisés par l’ovocyte. Pour obtenir une confirmation fonctionnelle, une paire de transcrits maternels (l’un détecté dans notre sondage précédent et l’autre étant une molécule reliée) ont été inhibés par « knock-down » dans des ovocytes. Les effets du knock-down de ces facteurs de transcription sont apparus avant la formation des blastocystes dû à une diminution de la capacité au clivage et celle à progresser après le stage de 8-cellules. L’analyse moléculaire des embryons knock-down survivants suggère qu’un de ces facteurs de transcription est un contrôleur crucial de l’activation du génome embryonnaire, qui représente une fenêtre développementale dans l’embryogenèse précoce. Dans la dernièr étude, nous avons testé si les facteurs de transcription d’intérêt sont modulés au niveau traductionnel. Des ARNm rapporteurs couplés à la GFP (Protéine fluorescente) contenant soit la version courte ou la version longue de la séquence 3’-UTR des deux molécules furent injectées dans des zygotes pour évaluer leur dynamique traductionnelle. Les résultats ont montré que les éléments cis-régulateurs localisés dans les 3’-UTRs contrôlent leur synchronisation traductionnelle et suggèrent une association entre la compétence développementale et la capacité de synthèse de ces protéines. Ceci conduit à l’idée que ces facteurs de transcription cruciaux sont aussi contrôlés au niveau traductionnel chez les embryons précoces. Les connaissances acquises ont joué un rôle essentiel pour définir le contrôle potentiel des molécules maternelles sur les embryons au début de leur développement. Cette étude nous montre aussi une utilisation potentielle de cette information ainsi que les nouveaux défis présents dans le secteur des technologies reproductives.

Safer and more efficient terminals: the role of movement, behaviour and evacuation simulation in design

Abstract not available

Athletic groin pain (part 2): a prospective cohort study on the biomechanical evaluation of change of direction identifies three clusters of movement patterns

Background: Athletic groin pain (AGP) is prevalent in sports involving repeated accelerations, decelerations, kicking and change-of-direction movements. Clinical and radiological examinations lack the ability to assess pathomechanics of AGP, but three-dimensional biomechanical movement analysis may be an important innovation. Aim: The primary aim was to describe and analyse movements used by patients with AGP during a maximum effort change-of-direction task. The secondary aim was to determine if specific anatomical diagnoses were related to a distinct movement strategy. Methods: 322 athletes with a current symptom of chronic AGP participated. Structured and standardised clinical assessments and radiological examinations were performed on all participants. Additionally, each participant performed multiple repetitions of a planned maximum effort change-of-direction task during which whole body kinematics were recorded. Kinematic and kinetic data were examined using continuous waveform analysis techniques in combination with a subgroup design that used gap statistic and hierarchical clustering. Results: Three subgroups (clusters) were identified. Kinematic and kinetic measures of the clusters differed strongly in patterns observed in thorax, pelvis, hip, knee and ankle. Cluster 1 (40%) was characterised by increased ankle eversion, external rotation and knee internal rotation and greater knee work. Cluster 2 (15%) was characterised by increased hip flexion, pelvis contralateral drop, thorax tilt and increased hip work. Cluster 3 (45%) was characterised by high ankle dorsiflexion, thorax contralateral drop, ankle work and prolonged ground contact time. No correlation was observed between movement clusters and clinically palpated location of the participant's pain. Conclusions: We identified three distinct movement strategies among athletes with long-standing groin pain during a maximum effort change-of-direction task. These movement strategies were not related to clinical assessment findings but highlighted targets for rehabilitation in response to possible propagative mechanisms. Trial registration number NCT02437942, pre results.

Thalamic modulation of the cortisal slow oscillation

Il est bien établi que le thalamus joue un rôle crucial dans la génération de l’oscillation lente synchrone dans le cortex pendant le sommeil lent. La puissance des ondes lente / delta (0.2-4 Hz) est un indicateur quantifiable de la qualité du sommeil. La contribution des différents noyaux thalamiques dans la génération de l’activité à ondes lentes et dans sa synchronisation n’est pas connue. Nous émettons l’hypothèse que les noyaux thalamiques de premier ordre (spécifiques) influencent localement l’activité à ondes lentes dans les zones corticales primaires, tandis que les noyaux thalamiques d’ordre supérieur (non spécifiques) synchronisent globalement les activités à ondes lentes à travers de larges régions corticales. Nous avons analysé les potentiels de champ locaux et les activités de décharges de différentes régions corticales et thalamiques de souris anesthésiées alors qu’un noyau thalamique était inactivé par du muscimol, un agoniste des récepteurs GABA. Les enregistrements extracellulaires multi-unitaires dans les noyaux thalamiques de premier ordre (VPM) et d’ordre supérieur (CL) montrent des activités de décharges considérablement diminuées et les décharges par bouffées de potentiels d’action sont fortement réduites après inactivation. Nous concluons que l’injection de muscimol réduit fortement les activités de décharges et ne potentialise pas la génération de bouffées de potentiel d’action à seuil bas. L’inactivation des noyaux thalamiques spécifiques avec du muscimol a diminué la puissance lente / delta dans la zone corticale primaire correspondante. L’inactivation d’un noyau non spécifique avec le muscimol a significativement réduit la puissance delta dans l’ensemble du cortex étudié. Nos expériences démontrent que le thalamus a un rôle crucial dans la génération de l’oscillation lente corticale.

Acousto-optic modulation of optical reflection properties in fiber Bragg gratings and the application in fiber lasers

This thesis aims to investigate the interaction of acoustic waves and fiber Bragg gratings (FBGs) in standard and suspended-core fibers (SCFs), to evaluate the influence of the fiber, grating and modulator design on the increase of the modulation efficiency, bandwidth and frequency. Initially, the frequency response and the resonant acoustic modes of a low frequency acousto-optic modulator (f < 1.2 MHz) are numerically investigated by using the finite element method. Later, the interaction of longitudinal acoustic waves and FBGs in SCFs is also numerically investigated. The fiber geometric parameters are varied and the strain and grating properties are simulated by means of the finite element method and the transfer matrix method. The study indicates that the air holes composing the SCF cause a significant reduction of the amount of silica in the fiber cross section increasing acousto-optic interaction in the core. Experimental modulation of the reflectivity of FBGs inscribed in two distinct SCFs indicates evidences of this increased interaction. Besides, a method to acoustically induce a dynamic phase-shift in a chirped FBG employing an optimized design of modulator is shown. Afterwards, a combination of this modulator and a FBG inscribed in a three air holes SCF is applied to mode-lock an ytterbium doped fiber laser. To improve the modulator design for future applications, two other distinct devices are investigated to increase the acousto-optic interaction, bandwidth and frequency (f > 10 MHz). A high reflectivity modulation has been achieved for a modulator based on a tapered fiber. Moreover, an increased modulated bandwidth (320 pm) has been obtained for a modulator based on interaction of a radial long period grating (RLPG) and a FBG inscribed in a standard fiber. In summary, the results show a considerable reduction of the grating/fiber length and the modulator size, indicating possibilities for compact and faster acousto-optic fiber devices. Additionally, the increased interaction efficiency, modulated bandwidth and frequency can be useful to shorten the pulse width of future all-fiber mode-locked fiber lasers, as well, to other photonic devices which require the control of the light in optical fibers by electrically tunable acoustic waves.

The insect repellent N,N-diethyl-m-toluamide (DEET) induces angiogenesis via allosteric modulation of the M3 muscarinic receptor in endothelial cells

International audience

Modulation of sea surface temperature warming in the Bay of Biscay by Loire and Gironde Rivers

The influence of Loire and Gironde River discharges over the sea surface temperature (SST) in the eastern Bay of Biscay (0.6º–36.6ºW, 44.2º–47.8ºW) was analyzed by means of two complementary databases (MODIS and OISST1/4). The area influenced by river plume showed a different SST when compared with the adjacent oceanic area for the months when the plume attains its highest extension (December, January, and February). Ocean was observed to warm at a rate of approximately 0.3ºC dec−1 while temperature at the area influenced by the rivers cooled at a rate of −0.15ºC dec−1 over the period 1982–2014. The mere presence of a freshwater layer is able to modulate the warming observed at adjacent ocean locations since the coastal area is isolated from the rest of the Bay. This nearshore strip is the only part of the Bay where changes in SST depend on North Atlantic Oscillation (NAO) but not on North Atlantic SST represented by the Atlantic Multidecadal Oscillation (AMO). These different cooling-warming trends are even more patent over the last years (2002–2014) under atmospheric favorable conditions for plume enhancement. River runoff increased at a rate on the order of 120 m3s−1dec−1 over that period and southwesterly winds, which favor the confinement of the plume, showed a positive and significant trend both in duration and intensity. Thus, the coastal strip has been observed to cool at a rate of −0.5°C dec−1.

The Pierre Auger Observatory scaler mode for the study of solar activity modulation of galactic cosmic rays

Since data-taking began in January 2004, the Pierre Auger Observatory has been recording the count rates of low energy secondary cosmic ray particles for the self-calibration of the ground detectors of its surface detector array. After correcting for atmospheric effects, modulations of galactic cosmic rays due to solar activity and transient events are observed. Temporal variations related with the activity of the heliosphere can be determined with high accuracy due to the high total count rates. In this study, the available data are presented together with an analysis focused on the observation of Forbush decreases, where a strong correlation with neutron monitor data is found.