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Marie-Soleil R. Smith

Other affiliations: Centre for Blood Research
Bio: Marie-Soleil R. Smith is an academic researcher from University of British Columbia. The author has contributed to research in topics: Medicine & Cotinine. The author has an hindex of 1, co-authored 2 publications receiving 2 citations. Previous affiliations of Marie-Soleil R. Smith include Centre for Blood Research.

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Journal ArticleDOI
TL;DR: The observation of oxidative damage in the form of 7,8-dihydro-8-oxo-deoxyguanosine (8-OxodG) DNA oxidative lesions accumulating with age has been a cornerstone of the free radical theory of aging.
Abstract: The free radical theory of aging, one of the nine suggested hallmarks of aging (López-Otín et al., 2016), implicates the gradual accumulation of oxidative cellular damage as a fundamental driver of cellular aging (Harman, 1956; Miquel et al., 1980). This theory has evolved over time to emphasize the role of free radical induced mitochondrial DNA (mtDNA) mutations and the accumulation of mtDNA deletions (Miquel et al., 1980; Cortopassi et al., 1992; Michikawa et al., 1999). Given the proximity of mtDNA to the electron transport chain, a primary producer of free radicals, it postulates that the mutations would promote mitochondrial dysfunction and concomitantly increase free radical production in a positive feedback loop. The observation of oxidative damage in the form of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) DNA oxidative lesions accumulating with age has been a cornerstone of the free radical theory of aging (Fraga et al., 1990).

31 citations

Journal ArticleDOI
TL;DR: Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to further elucidate the effect of In STIs on embryonic development, as well as their long-term safety following in utero exposure.
Abstract: BACKGROUND Each year, approximately 1.1 million children are exposed in utero to HIV antiretrovirals, yet their safety is often not well characterized during pregnancy. The Tsepamo study reported a neural tube defect signal in infants exposed to the integrase inhibitor (InSTI) dolutegravir from conception, suggesting that exposure during early fetal development may be detrimental. METHODS The effects of InSTIs on two human embryonic stem cell (hESC) lines were characterized with respect to markers of pluripotency, early differentiation, and cellular health. Additionally, fetal resorptions following exposure to InSTIs from conception were analyzed in pregnant mice. RESULTS At sub-therapeutic concentrations, second-generation InSTIs bictegravir, cabotegravir, and dolutegravir decreased hESC counts, pluripotency, and induced dysregulation of genes involved in early differentiation. At therapeutic concentrations, bictegravir induced substantial hESC death and fetal resorptions. Notably, first-generation InSTI raltegravir did not induce any hESC toxicity or differentiation, at any concentration tested. CONCLUSIONS Exposure to some InSTIs, even at sub-therapeutic concentrations, can induce adverse effects in hESCs and pregnant mice. Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to further elucidate the effect of InSTIs on embryonic development, as well as their long-term safety following in utero exposure.

3 citations

Journal ArticleDOI
23 Aug 2022-AIDS
TL;DR: In this paper , the authors evaluated the effect of DTG-containing antiretroviral therapy (cART) on cellular and mitochondrial health following exposure to current cART regimens at pharmacological concentrations.
Abstract: Objectives: Given the success of combination antiretroviral therapy (cART) in treating HIV viremia, drug toxicity remains an area of interest in HIV research. Despite newer integrase strand transfer inhibitors (InSTIs), such as dolutegravir (DTG) and raltegravir (RAL), having excellent clinical tolerance, there is emerging evidence of off-target effects and toxicities. Although limited in number, recent reports have highlighted the vulnerability of mitochondria to these toxicities. The aim of the present study is to quantify changes in cellular and mitochondrial health following exposure to current cART regimens at pharmacological concentrations. A secondary objective is to determine whether any cART-associated toxicities would be modulated by human telomerase reverse transcriptase (hTERT). Methods: We longitudinally evaluated markers of cellular (cell count, apoptosis), and mitochondrial health [mitochondrial reactive oxygen species (mtROS), membrane potential (MMP) and mass (mtMass)] by flow cytometry in WI-38 human fibroblast with differing hTERT expression/localization and peripheral blood mononuclear cells. This was done after 9 days of exposure to, and 6 days following the removal of, seven current cART regimens, including three that contained DTG. Mitochondrial morphology was assessed by florescence microscopy and quantified using a recently developed deep learning-based pipeline. Results: Exposure to DTG-containing regimens increased apoptosis, mtROS, mtMass, induced fragmented mitochondrial networks compared with non-DTG-containing regimens, including a RAL-based combination. These effects were unmodulated by telomerase expression. All effects were fully reversible following removal of drug pressure. Conclusion: Taken together, our observations indicate that DTG-containing regimens negatively impact cellular and mitochondrial health and may be more toxic to mitochondria, even among the generally well tolerated InSTI-based cART.

2 citations

Posted ContentDOI
12 Sep 2020-bioRxiv
TL;DR: The concordance between self-reported smoking and plasma cotinine concentration among participants enrolled in two related cohorts of vulnerable individuals shows that participant surveying in a non-judgemental context can lead to accurate and robust self-report data.
Abstract: Background: Stigma associated with tobacco smoking, especially during pregnancy, may lead to underreporting and possible bias in studies relying on self-reported smoking data. Cotinine, a nicotine metabolite with a ~20h half-life in blood, is often used as a biomarker of smoking. The objective of this study was to examine the concordance between self-reported smoking and plasma cotinine concentration among participants enrolled in two related cohorts of vulnerable individuals: human immunodeficiency virus (HIV)-positive and HIV-negative pregnant women enrolled in the CARMA-PREG cohort and HIV-positive and HIV-negative non-pregnant women and men enrolled in the CARMA-CORE cohort. Methods: For HIV-positive (n=76) and negative (n=24) pregnant women, plasma cotinine was measured by ELISA in specimens collected during the third trimester, between 28 and 38 weeks of gestation. Plasma cotinine was also measured in HIV-positive (n=43) and negative (n=57) women and men enrolled in the CARMA-CORE cohort. Results: Self-reported smokers were more likely to have low income (p<0.001) in both cohorts, and to deliver preterm (p=0.007) in CARMA-PREG. In the CARMA-PREG cohort, concordance between plasma cotinine was 95% for self-reported smoking, and 89% for self-reported non-smoking. In the CARMA-CORE cohort we observed similarly high concordances of 96% and 92% for self-reported smoking and non-smoking, respectively. In this sample, the odds of discordance between self-reported smoking status and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others. Taken together, the overall concordance between plasma cotinine and self-reported data was 94% with a Cohen9s kappa coefficient of 0.860 among all participants. Conclusions: Given the high proportion of vulnerable people in the CARMA-PREG and CARMA-CORE cohorts, our results may not be fully generalizable to the general population. However, they demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report data. Implications: Reliable self-reported smoking data is necessary to account for smoking status in subsequent studies. Our results suggest that future studies should ensure that study participants feel sale to speak candidly to non-judgemental research staff to obtain reliable self-report data.

1 citations

Journal ArticleDOI
TL;DR: In this paper , the authors evaluated concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts.
Abstract: Understanding the true burden of tobacco smoking on adverse pregnancy outcomes is critical in generating appropriate interventions to improve outcomes. Self-reporting of human behaviour that is associated with stigma is associated with underreporting in general and may bias the impact of smoking in studies; however, self-reporting is frequently the most practical method of gleaning this information. The objective of this study was to evaluate concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts. A total of 100 pregnant women (76 living with HIV [LWH] and 24 negative controls) in their third trimester, and 100 men and non-pregnant women (43 LWH and 57 negative controls) were included. Among all participants, 43 pregnant women (49% LWH and 25% negative controls) and 50 men and non-pregnant women (58% LWH and 44% negative controls) were self-reported smokers. The odds of discordance between self-reported smoking and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others, but were significantly increased, regardless of self-reported status, among people LWH compared to negative controls. The overall concordance between plasma cotinine and self-reported data among all participants was 94% with a sensitivity and specificity of 90% and 96%, respectively. Taken together, these data demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report smoking data among both persons LWH and not, including in the context of pregnancy.

Cited by
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Journal ArticleDOI
TL;DR: Folate Siatus in Pregnancy confirms previous findings that 300 "g.
Abstract: Folate Siatus in Pregnancy: Report confirms previous findings that 300 \"g. folic acid daily is a suitable supplement (p. 356). Myocardial Infarction: Oxygen therapy probably worth while since tissue oxygenation appears to be improved by it, despite reduction it causes in cardiac output (p. 360). Ventricular Dysrhythmias: Occurred after recovery from infarction in 11 out of 142 patients, and proved fatal in seven (p. 364).

83 citations

Journal ArticleDOI
TL;DR: In this paper , a review highlights various miniaturized surface engineered biosensors for the detection of reactive oxygen species (ROS) and highlights the developed sensors for detection through the help of various illustrative schemes.

5 citations

Journal ArticleDOI
TL;DR: In this paper , the authors investigated the anti-aging properties of Rhododendron nivale Hook (RNEA) and found that it possesses antiaging properties and the interaction of gut microbiota with RNEA is responsible for its antiaging effects.

5 citations

Posted ContentDOI
19 Feb 2022-bioRxiv
TL;DR: The results suggest that under normal in vivo conditions methionine oxidation is a biologically regulated process rather than a result of stochastic chemical damage.
Abstract: The oxidation of methionine side chains has emerged as an important posttranslational modification of proteins. A diverse array of low-throughput and targeted studies have suggested that the oxidation of methionine residues in select proteins can have diverse impacts on cell physiology, ranging from detrimental effects on protein structure and stability to functional roles in cell signaling. Despite its importance, the large-scale investigation of methionine oxidation in a complex matrix, such as the cellular proteome, has been historically hampered by technical limitations. Herein we report a methodology, Methionine Oxidation by Blocking (MobB), that allows for accurate and precise quantification of low levels of methionine oxidation typically observed in vivo. To demonstrate the utility of this methodology, we applied MobB to the brain tissues of young (6 m.o.) and old (20 m.o.) mice and identified over 280 novel sites for in vivo methionine oxidation. We further demonstrated that oxidation stoichiometries for specific methionine residues are highly consistent between individual animals and methionine sulfoxides are enriched in clusters of functionally related gene products including membrane and extracellular proteins. However, we did not detect significant changes in methionine oxidation in brains of old mice. Our results suggest that under normal in vivo conditions methionine oxidation is a biologically regulated process rather than a result of stochastic chemical damage.

4 citations

Journal ArticleDOI
TL;DR: In this article , a methodology called methionine oxidation by blocking (MobB) was proposed for quantifying low levels of methionines typically observed in vivo, which can have diverse impacts on cell physiology, ranging from detrimental effects on protein stability to functional roles in cell signaling.
Abstract: The oxidation of methionine has emerged as an important post-translational modification of proteins. A number of studies have suggested that the oxidation of methionines in select proteins can have diverse impacts on cell physiology, ranging from detrimental effects on protein stability to functional roles in cell signaling. Despite its importance, the large-scale investigation of methionine oxidation in a complex matrix, such as the cellular proteome, has been hampered by technical limitations. We report a methodology, methionine oxidation by blocking (MobB), that allows for accurate and precise quantification of low levels of methionine oxidation typically observed in vivo. To demonstrate the utility of this methodology, we analyzed the brain tissues of young (6 m.o.) and old (20 m.o.) mice and identified over 280 novel sites for in vivo methionine oxidation. We further demonstrated that oxidation stoichiometries for specific methionine residues are highly consistent between individual animals and methionine sulfoxides are enriched in clusters of functionally related gene products including membrane and extracellular proteins. However, we did not detect significant changes in methionine oxidation in brains of old mice. Our results suggest that under normal conditions, methionine oxidation may be a biologically regulated process rather than a result of stochastic chemical damage.

4 citations