Influence des agonistes dopaminergiques et des facteurs de transcriptions sur la réponse cellulaire face au stress oxydant

[Facteur de transcription nucléaire orphelin Nur77 ; MPP+ (Ion 1-methyl-4-phenylpyridinium)]

Comparative Analysis of the Frequency and Distribution of Stem and Progenitor Cells in the Adult Mouse Brain

cells (NSCs) and progenitor cells, but it cannot discriminate between these two populations. Given two assays have purported to overcome this shortfall, we performed a comparative analysis of the distribution and frequency of NSCs and progenitor cells detected in 400 m coronal segments along the ventricular neuraxis of the adult mouse brain using the neurosphere assay, the neural colony forming cell assay (N-CFCA), and label-retaining cell (LRC) approach. We observed a large variation in the number of progenitor/stem cells detected in serial sections along the neuraxis, with the number of neurosphereforming cells detected in individual 400 m sections varying from a minimum of eight to a maximum of 891 depending upon the rostral-caudal coordinate assayed. Moreover, the greatest variability occurred in the rostral portion of the lateral ventricles, thereby explaining the large variation in neurosphere frequency previously reported. Whereas the overall number of neurospheres (3730 276) or colonies (4275 124) we detected along the neuraxis did not differ significantly, LRC numbers were significantly reduced (1186 188, 7 month chase) in comparison to both total colonies and neurospheres. Moreover, approximately two orders of magnitude fewer NSC-derived colonies (50 10) were detected using the N-CFCA as compared to LRCs. Given only 5% of the LRCs are cycling (BrdU/Ki-67) or competent to divide (BrdU/Mcm-2), and proliferate upon transfer to culture, it is unclear whether this technique selectively detects endogenous NSCs. Overall, caution should be taken with the interpretation and employment of all these techniques

HIV Prevention Via Mobile Messaging for Men Who Have Sex With Men (M-Cubed): Protocol for a Randomized Controlled Trial

Background: Men who have sex with men (MSM) continue to be the predominately impacted risk group in the United States HIV epidemic and are a priority group for risk reduction in national strategic goals for HIV prevention. Modeling studies have demonstrated that a comprehensive package of status-tailored HIV prevention and care interventions have the potential to substantially reduce new infections among MSM. However, uptake of basic prevention services, including HIV testing, sexually transmitted infection (STI) testing, condom distribution, condom-compatible lubricant distribution, and preexposure prophylaxis (PrEP), is suboptimal. Further, stronger public health strategies are needed to promote engagement in HIV care and viral load suppression among MSM living with HIV. Mobile health (mHealth) tools can help inform and encourage MSM regarding HIV prevention, care, and treatment, especially among men who lack access to conventional medical services. This protocol details the design and procedures of a randomized controlled trial (RCT) of a novel mHealth intervention that comprises a comprehensive HIV prevention app and brief, tailored text- and video-based messages that are systematically presented to participants based on the participants’ HIV status and level of HIV acquisition risk. Objective: The objective of the RCT was to test the efficacy of the Mobile Messaging for Men (M-Cubed, or M3) app among at least 1200 MSM in Atlanta, Detroit, and New York. The goal was to determine its ability to increase HIV testing (HIV-negative men), STI testing (all men), condom use for anal sex (all men), evaluation for PrEP eligibility, uptake of PrEP (higher risk HIV-negative men), engagement in HIV care (men living with HIV), and uptake of and adherence to antiretroviral medications (men living with HIV). A unique benefit of this approach is the HIV serostatus-inclusiveness of the intervention, which includes both HIV-negative and HIV-positive MSM. Methods: MSM were recruited through online and venue-based approaches in Atlanta, Detroit, and New York City. Men who were eligible and consented were randomized to the intervention (immediate access to the M3 app for a period of three months) or to the waitlist-control (delayed access) group. Outcomes were evaluated immediately post intervention or control period, and again three and six months after the intervention period. Main outcomes will be reported as period prevalence ratios or hazards,depending on the outcome. Where appropriate, serostatus/risk-specific outcomes will be evaluated in relevant subgroups. Men randomized to the control condition were offered the opportunity to use (and evaluate) the M3 app for a three-month period after the final RCT outcome assessment. Results: M3 enrollment began in January 2018 and concluded in November 2018. A total of 1229 MSM were enrolled. Datacollection was completed in September 2019.Conclusions: This RCT of the M3 mobile app seeks to determine the effects of an HIV serostatus–inclusive intervention on the use of multiple HIV prevention and care-related outcomes among MSM. A strength of the design is that it incorporates a large sample and broad range of MSM with differing prevention needs in three cities with high prevalence of HIV among MSM

Mathematics and Computers in Simulation xxx (2003) xxx-xxx Real-time computer control of a multilevel converter using the mathematical theory of resultants

Abstract The mathematical theory of resultants is used to compute the switching angles in a multilevel converter so that it produces the required fundamental voltage while at the same time cancels out unwanted order harmonics. Experimental results are given for the three dc source case. It is shown that for a range of the modulation index the switching angles can be chosen to produce the desired fundamental while at the same time the fifth and seventh harmonics are identically zero

KEITH CHIASSON

Influence des agonistes dopaminergiques et des facteurs de transcriptions sur la réponse cellulaire face au stress oxydant Thèse présentée à la Faculté des études supérieures de l'Université Laval dans le cadre du programme de doctorat en Neurobiologie pour l'obtention du grade de Philosophiae Doctor (Ph. D.

17β-estradiol delays 6-OHDA-induced apoptosis by acting on Nur77 translocation from the nucleus to the cytoplasm

Nuclear receptors (Nurs) represent a large family of gene expression regulating proteins. Gathering evidence indicates an important role for Nurs as transcription factors in dopamine neurotransmission. Nur77, a member of the Nur superfamily, plays a role in mediating the effects of antiparkinsonian and neuroleptic drugs. Besides, Nur77 survival and apoptotic roles depend largely on its subcellular localization. Estrogens are known for their neuroprotective properties, as demonstrated in animal and clinical studies. However, their action on Nur77 translocation pertaining to neuroprotection has not been investigated yet. The aim of our study was to perform a kinetic study on the effect of neurotoxic 6-hydroxydopamine (6-OHDA) and 17β-estradiol (E2) on the subcellular localization of Nur77 with reference to the modulation of apoptosis in PC12 cells. Our results demonstrate that E2 administration alone does not affect Nur77 cytoplasmic/nuclear ratio, mRNA levels, or apoptosis in PC12 cells. The neurotoxin 6-OHDA significantly enhances cytoplasmic localization of Nur77 after merely 3 h, while precipitating apoptosis. 6-OHDA also increases Nur77 transcription, which could partly explain the rise in cytoplasmic localization of the protein. Finally, treatment with both E2 and 6-OHDA delays Nur77 accumulation in the cytoplasm and delays cell death for a few hours in our cellular paradigm. Pre-treatment with E2 does not alter the increase in levels of Nur77 mRNA produced by 6-OHDA, suggesting that a raise in nuclear translocation is likely responsible for the stabilization of the cytoplasmic/nuclear ratio until 6 h. These results suggest an intriguing cooperation between E2 and Nur77 toward cellular fate guidance

Stimulant Use and Study Protocol Completion: Assessing the Ability of Men Who Have Sex with Men to Collect Dried Blood Spots for Laboratory Measurement of HIV Viral Load

Stimulant use is associated with higher HIV viral load (VL) and sexual HIV transmission risk among men who have sex with men (MSM) living with HIV. There is little research on willingness of drug users living with HIV to fully participate in studies, especially those involving self-collection of biomarker data. This study presents findings from an at-home dried blood spot collection study measuring laboratory-quantified VL among U.S. HIV-positive MSM who reported high-risk sexual behavior and/or suboptimal antiretroviral therapy (ART) adherence to assess the association between drug-use behavior and (1) ability to complete a study protocol and (2) VL outcomes. Among recruited participants (n = 766), 35% reported stimulant drug use (amphetamines, cocaine, crack, crystal meth, ecstasy, or a combination of stimulant drugs), 39% reported using other drugs (heroin, marijuana, prescription opioids, and others), and 27% reported no drug use in the past 3 months. In all, 61% of enrolled participants completed the study protocol. Stimulant drug users were less likely (ARR 0.84; 95% CI 0.72-0.98) to complete the protocol than other drug users. Furthermore, other drug users were significantly less likely than non-drug users (ARR 0.52; 95% CI 0.28-0.97) to have an HIV VL result ≥ 1500 copies/mL. This study provides important estimates regarding the likelihood of participation in biomedical research activities among HIV-positive MSM with varying drug-use behaviors, showing that it is feasible to conduct such biomedical studies with drug-using MSM who report high-risk sexual behavior and struggle with their ART adherence