No description available.

In recent times, endocrine disrupting chemicals (EDCs) have been associated with the rise in neurodevelopmental disorders such as autism, attention deficit hyperactivity disorder (ADHD) and decreased intelligence quotient (IQ) in children. This effect is suspected to be induced at pre-/peri-natal development, via an alteration in hormonal signaling, thus interfering with neuronal differentiation, with subsequent effect on normal brain development and function in exposed children. This issue increases the need for chemical screening for potential developmental neurotoxicity (DNT) effect. The current available EDC induced DNT test guideline is based on in-vivo testing that requires animal use. Here, a multipotent neural progenitor cell line, the C17.2 cell-line, generated from neural stem cells of the external germinal layer of mouse cerebellum, with potential to differentiate to neurons or astrocytes, is introduced for in-vitro EDC induced DNT testing. This project focused on optimizing the C17.2 cell-line for the detection of EDC-induced DNT with emphasis on the disruption of the oestrogen, androgen, and thyroid hormone systems. It aimed at validating the involvement of oestrogen, androgen, and thyroid hormone on molecular and cellular endpoints relevant for the differentiation of the C17.2 cells.  Herein, the cells were exposed to the hormonal agonist and antagonist at a range of concentrations for a 10-day differentiation period. After exposure, LDH, viability assay and morphological changes (percentage of neurons in culture and neurite outgrowth) were evaluated. The results showed no morphological changes induced by androgen receptor (AR) agonist/antagonist at relevant physiological concentrations. The thyroid receptor (TR) agonist and antagonist on the other hand showed a response in the form of increased neurite outgrowth in relation to the negative control at a concentration range of 40-200 nM and 40 nM respectively. The oestrogen receptor (ER) antagonist at 100 nM also increased percentage neuron in culture. Additionally, in-silico analysis of microarray and RNA sequencing data were used to map out target genes regulated by ER, AR and TR and involved in neurodevelopment. With this approach, 29 marker genes were identified. Validation of the marker genes by means of gene expression (qPCR) was carried out, ER and TR agonist/antagonist were observed to modulate the expression of examined genes. In summary, the model could not be established for detecting EDC induced DNT via androgenic and oestrogenic pathway, while it is a promising model for identifying DNT induced by thyroid hormone signalling disruption.

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebocontrolled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment.

No description available.

Syftet med studien är att undersöka huruvida den kontorsarbetande kvinnan blir påverkad av menscykelns hormonella skiftningar i arbetslivet, i termer av arbetsprestation och arbetsmiljö. Därtill undersöks huruvida kvinnan ställer sig till arbetsrelaterade anpassningar med hänsyn till påverkan av de hormonella skiftningarna. Datan är insamlad genom kvantitativ metod i form av enkäter på både svenska och engelska. Enkäterna distribuerades på de sociala plattformarna LinkedIn och Facebook tillsammans med en infografisk bild som innehöll fakta om könshormoners påverkan av kroppen. Resultatet indikerar att de kontorsarbetande kvinnorna är måttligt eller starkt påverkade av menscykelns hormonella skiftningar i arbetet. Dessutom framkommer det att en majoritet av respondenterna är positiva till att implementera arbetsrelaterade anpassningar avseende dessa hormonella förändringar. Baserat på datainsamlingen och de valda teoretiska ramverken kan det konstateras att arbetslivet inte alltid är anpassat utefter kvinnors biologiska förutsättningar, och att kvinnors arbetsmiljö och arbetsprestation skulle förbättras såvida arbetsrelaterade anpassningar genomfördes. Vidare är det möjligt att konstatera att ett arbetsklimat anpassat för båda könen skulle ge en ömsesidig vinning för både kvinnorna och företagen. / The purpose of the study is to examine whether the female office worker is affected by the menstrual cycle’s hormonal fluctuations in the workplace, in terms of work performance and work environment. Additionally, it investigates whether women are receptive to workplace adjustments considering the impact of hormonal fluctuations. The data was collected through a quantitative method using surveys in both Swedish and English. The surveys were distributed on the social platforms LinkedIn and Facebook along with an infographic containing facts about the influence of sex hormones on the body. The results indicate that female office workers are moderately or strongly affected by hormonal fluctuations during the menstrual cycle at work. Furthermore, the results show that the majority of respondents are positive towards workplace adjustments regarding hormonal fluctuations during the menstrual cycle. Based on the data collection and the selected theoretical frameworks, it can be concluded that the workplace is not always tailored to women's biological conditions, and that women's work environment and performance would improve if work-related adaptations were implemented. Furthermore, it can be concluded that a work environment adapted for both genders would provide mutual benefits for both the women and the companies.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Thesis (Ph. D.)--University of Virginia, 2008. / Includes bibliographical references. Also available online through Digital Dissertations.

Objectif : Étudier l'association entre l’utilisation de contraceptifs hormonaux et le risque d'acquisition du VIH-1 chez les femmes au Malawi, en Afrique du Sud, en Zambie et au Zimbabwe. Devis : Analyses secondaires de 2887 femmes âgées de 17-55 ans ayant participé à l’étude HPTN 035, une étude de phase II/IIb sur l’efficacité de deux gels microbicides pour prévenir la transmission du VIH chez les femmes à risque. Méthodes : L'association entre l'utilisation de contraceptifs hormonaux et le risque d'acquisition du VIH-1 a été évaluée en utilisant des modèles de Cox. Des risques relatifs sont estimés où le groupe de référence est celui des femmes qui n’utilisent pas de contraceptifs hormonaux. De plus, un modèle multivarié de Cox est utilisé afin de contrôler pour les facteurs potentiellement confondants. Résultats : Les contraceptifs injectables ont été utilisés par 52,1% des femmes, alors que les contraceptifs oraux ont été utilisés par 20,7% de celles-ci. Pendant l'étude, il y a eu 192 séroconversions. L'incidence observée du VIH était de 2,28; 4,19 et 4,69 pour 100 personne-années pour les contraceptifs oraux, injectables et non hormonaux, respectivement. Lors de l’analyse multivariée, nous n'avons trouvé aucune association significative entre l’usage des contraceptifs hormonaux et l’acquisition du VIH-1. Le risque relatif ajusté (RRa) pour les contraceptifs oraux est de 0,573 (IC de 95% : [0,31-1,06]) et 0,981 (IC de 95% : [0,69 ; 1,39]) pour les contraceptifs injectables. Conclusions : Bien que cette étude ne démontre pas d’association entre l’usage des contraceptifs hormonaux et le VIH-1, nous concluons toutefois que ces méthodes de contraception ne protègent pas contre le VIH-1, et il est ainsi recommandé aux femmes utilisant des hormones contraceptives de toujours utiliser le condom pour prévenir l'infection au VIH-1. / Objective: To investigate the association between the use of hormonal contraceptive and the risk of acquiring HIV-1 infection in women from Malawi, South Africa, Zambia and Zimbabwe. Design: Secondary analyses of 2887 women aged 17-55 years who participated in the HPTN 035 trial, a Phase II/IIb trial on the efficacy of two microbicide gels to prevent HIV transmission in women at risk in Africa. Methods: The association between the use of hormonal contraceptive and the risk of acquiring HIV-1 was evaluated using Cox proportionnal models. Relative risks of exposed women were estimated using as a reference group the women who do not use hormonal contraceptives. In addition, a multivariate Cox model was used to control for potentially confounding factors. Results: Injectable contraceptives were used by 52.1 % of women, while oral contraceptives were used by 20.7% of them. During the study, there were 192 seroconversions. The observed HIV-1 incidence was 2.28, 4.19 and 4.69 per 100 woman-years for oral, injectable and non-hormonal contraceptive users, respectively. In multivariate analysis, we found no significant association between the use of hormonal contraceptives and HIV-1 acquisition. The adjusted relative risk (aRR) for oral contraceptives was 0.573 (95% CI: [0.31 to 1.06]) and 0.981 (95% CI: [0.69, 1.39]) for injectable contraceptives. Conclusions: Although this study did not demonstrate an association between hormonal contraceptive use and the risk of HIV-1 infection, we conclude, however, that these methods of contraception do not protect against HIV-1, and it is thus recommended that women using contraceptive hormones always use condoms to prevent HIV-1.

A acidez do solo é um dos principais fatores limitantes à produção vegetal. A toxicidade por alumínio, que ocorre apenas a pH baixo, tem sido extensamente investigada, enquanto o estresse causado pelo pH baixo tem recebido pouca atenção. Os estudos nesta área quase sempre presumem efeitos aditivos, e portanto independentes, da toxicidade por Al3+ e H+. Este provavelmente não é o caso, sendo que o pH baixo pode ser um fator de predisposição das células ao Al3+. As evidências indicam que o pH baixo causa desarranjos na parede de células em crescimento, gerando estresse que pode comprometer a sua funcionalidade e integridade. É provável que a susceptibilidade a este estresse deve ser dependente da pressão de turgor. Por sua vez, o metabolismo oxidativo e a geração de espécies reativas de oxigênio (ROS) na parede celular podem modular a sua extensibilidade por romper ou criar ligações dentro ou entre cadeias de polissacarídeo. Há grande interesse em se conhecer se, à semelhança do que ocorre em leveduras, as células vegetais possuem um sistema de percepção e resposta a estresse da parede. Os pêlos radiculares em crescimento são sensíveis a pH baixo e estresse hipo-osmótico e constituem um bom modelo experimental para estes estudos. Os objetivos deste trabalho foram: a) Otimizar um sistema experimental para o estudo de pêlos radiculares de tomateiro (Solanum lycopersicum L. cv Micro-Tom); b) Avaliar as respostas dos pêlos radiculares ao estresse por pH baixo e hipo-osmolaridade; c) Examinar o papel da modulação oxidativa da parede celular nestas respostas; e d) Avaliar a resposta de diferentes mutantes hormonais de Micro-Tom a estes fatores de estresse. Os principais parâmetros avaliados foram a taxa de alongamento (µm.min-1) e a freqüência de rompimento dos pêlos. Tanto o estresse por pH baixo quanto choques hipo-osmóticos resultaram em taxas de alongamento significativamente diminuídos e o rompimento de pêlos radiculares, mas os efeitos dos tratamentos hipo-osmóticos foram mais marcantes. Uma curva de resposta frente à osmolaridade da solução externa revelou que a taxa de alongamento aumentou com a diminuição da osmolaridade até alcançar um limiar em que houve redução drástica da taxa de alongamento e começou-se a observar o rompimento de pêlos. Também se observou uma interação entre hipo-osmolaridade e pH baixo. O emprego do inibidor difenileno iodônio não forneceu evidências do envolvimento de NADPH oxidases da membrana plasmática na resposta de pêlos radiculares a choque hipo-osmótico ou pH baixo. Já no caso do inibidor ácido salicilhidroxâmico, encontrou-se evidências do envolvimento de peroxidases da parede. Nos mutantes hormonais dgt (pouco sensível a auxina) e epi (super produtor de etileno), mas não em not (deficiente em ácido abscísico), os pêlos radiculares apresentaram uma melhor resposta de ajustamento a choque hipo-osmótico do que Micro-Tom, reduzindo o alongamento e o rompimento dos pêlos. Este trabalho fornece fortes evidências de que os pêlos radiculares possuem um mecanismo de percepção e resposta a estresse da parede visando à manutenção de sua integridade e que apresentam bom potencial como sistema modelo nesta linha de pesquisa / Soil acidity is a major factor limiting plant growth worldwide. Aluminum toxicity, which occurs only at low pH, has been extensively studied, whereas low pH stress has received much less attention. Studies on Al3+ and H+ toxicity make the underlying assumption that the effects of these stress factors are additive, and, therefore independent of each other. However, this is most likely not the case and low pH may be a factor which increases susceptibility to further injury by Al3+. There is evidence that low pH causes disruption in cell wall structure of growing cells, which might jeopardize cell wall functionality and integrity. It is likely that turgor pressure plays an important role in cell wall stress caused by low pH. The apoplastic metabolism of reactive oxygen species (ROS) can modulate cell wall extensibility by making or breaking bonds within and between cell wall polysaccharides. A major question is whether, similarly to yeast, plant cells have a cell wall integrity signaling and response system. Growing root hairs are sensitive to low pH and hypo-osmotic stress and are potentially good experimental systems for such investigations. The objectives of this study were: a) Optimize an experimental system to examine tomato (Solanum lycopersicum L. cv Micro-Tom) root hairs; b) Examine the response of root hairs to low pH and hypo-osmotic stress; c) Examine the role of oxidative modulation of the cell wall in these responses; and d) Evaluate the response of different hormonal mutants of Micro-Tom to these stress factors. Root hair elongation rates (µm.min-1) and the frequency of cell bursting were the major experimental parameters which were evaluated. Both low pH and, more markedly, hypo-osmotic stress caused significant reductions in elongation rates and the bursting of root hair tips. In a response curve to varying osmolarities of the external medium, root hair elongation rates increased with decreasing osmolarities until a threshold was reached and elongation rates decreased drastically and the bursting of root hairs began to be observed. Interactions between low pH and hypo-osmolarity were observed. The use of the inhibitor diphenylene iodonium (DPI) did not provide evidence for the involvement of plasma membrane NADPH in the response of root hairs to low pH and hypo-osmotic shock. However, a role for cell wall peroxidases was provided by use of the inhibitor salicylhydroxamic acid (SHAM). Root hairs of the hormonal mutants dgt (low sensitivity to auxin) and epi (ethylene super producer), but not not (deficient in abscisic acid), displayed a more effective response to hypo-osmotic shock than Micro-Tom, by decreasing elongation rates and cell bursting to a greater degree. This study provides strong evidence to suggest that root hairs have a cell wall integrity response system and that root hairs are potentially good cell model systems for such research