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No description available.

Following decades of research on stress and its impact on behaviour, it is now widely accepted that selective psycho-pathologies, in particular clinical depression are more prevalent in humans with prior history of life-stress events. Interest in stress has led to questions about how it might affect the physiology and behaviour of animals exposed indirectly during gestational development. Not unexpectedly gestational stress has been shown to affect the offspring in several ways: endocrine responses to stress are elevated, fear, arousal and affective disturbances are all subject to vary if the pregnant animal is subjected to periods of aversive stimulation. Beginning in 1997, Michael Meaney of McGill University produced a series of publications suggesting that peri-natal events influence offspring and infant development, not via physical discomfort or physiological disturbance, but does so through modifications of maternal behaviour. Highly nurturant mothers (those who engage in active arched-back nursing (ABN), and spend more time licking and grooming (L/G) their pups), programme their offspring with improved cognitive abilities, decreased anxiety and fear, and reduced HPA axis hormone secretion. Low-nurturant mothers, who engage in less ABN and less L/G, tend to programme the opposite responses in their offspring. Our initial foray into this field was to investigate if gestational stress might also produce responses in the offspring via changes in maternal behaviour, and indeed ABN and L/G were reduced in dams which were subjected to gestational stress. We queried why stressed Dams would be less maternal towards their infants, and tested gestationally-stressed Dams in the Porsolt test for depressive-like behaviour. Our results suggested that these stressed Dams were actually depressed and this resulted in less maternal behaviour. Human mothers with depression are also less maternal and have been shown to divest themselves of infant care much like our prenatally-stressed Dams. On this basis we have proposed that gestational stress induced decrements in maternal behaviour represent a novel rat model for postnatal depression with face and construct validities. In the present work we have attempted to replicate the findings of Smythe¿s group (Smith et al., 2004), and have investigated the potential for antidepressants to alter the influence of gestational stress on maternal behaviours and depressive-like response, and whether or not the offspring¿ are modified by maternal treatment with ant-depressants. Approximately 140 time-mated, lister hooded rats were generated in house, and subjected to gestational stress on days 10-20 (1hr restraint/day) or remained undisturbed in their home cages. Following birth, cohorts of control and stressed Dams were administered vehicle or an antidepressant (imipramine 15mg/kg; or sertraline 10mg/kg) once daily until postnatal day 10. We assessed maternal Porsolt activity, nurturance (ABN, L/G, nest building) and anxiety-like behaviour in the elevated plus maze (EPM). Representative offspring of each Dam¿s treatment conditions were maintained post weaning and assessed in the Porsolt and EPM to determine if any changes in maternal behaviour elicited by the antidepressants altered their behavioural programming. Our findings confirm that Dams show depressive-like symptoms following gestational stress, and that administration of antidepressants to the Dams reduces depressive-like behaviour and increased maternal care. We propose that rat gestational stress is a putative model for human postnatal depression. Prenatal stress effects on maternal behaviour in the rat Dam represent a novel, and innovative model for human postnatal depression. / Ministry of Defence, Prince Sultan Military College of Health Sciences and the Saudi Culture Bureau

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No description available.

Approximately 10% of pregnant women take antidepressants. Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, has been shown to alter serotonergic signaling in the brain. However, the effects of SSRIs on peripheral serotonin (5HT) synthesis and/or signaling have largely been ignored. Serotonin in the gut is critical for intestinal function and dysregulation of this pathway is associated with intestinal disease. Therefore, the goal of this study was to determine the effects of perinatal exposure to the SSRI fluoxetine (Prozac®) on intestinal health in the offspring. Dams were given vehicle or fluoxetine hydrochloride (FLX 10 mg/kg/d; N=15) for 2 weeks prior to mating until weaning. We assessed markers of serotonergic signaling, inflammation, and composition of the gut microbiota in the offspring. Male offspring of fluoxetine-treated dams had significantly elevated serum levels of 5-HT and decreased expression of the 5HT2A receptor and MAO. In female offspring there was no effect of SSRI exposure to alter any components of serotonergic signaling. Although we did not find any evidence of increased inflammation following fluoxetine exposure, there were significant alterations in the composition of the gut microbiota in the exposed offspring. Male offspring of SSRIs-exposed mothers had changes in key components of the gut serotonergic system in association with elevated levels of serum 5-HT and alterations in the gut microbiota in adulthood. The impact of these changes on intestinal health and the reasons for the sex specific effects remain to be determined. / Thesis / Master of Science in Medical Sciences (MSMS)

In aquatic turtles, females select nest sites that have a high degree of solar exposure, and exploit recently tilled agricultural fields for nesting, presumably because of increased solar exposure and/or easier nest excavation, and the importance of incubation temperature on survival and offspring phenotype. These same disturbed sites are often contaminated by pollutants and turtles can incorporate high levels of pollutants into their eggs which negatively impact hatch success. For my M.S. research, I investigated turtle nest site selection in a system dominated by agricultural and industrial land use, the impact of crop growth on the thermal and hydric dynamics of turtle nests, and I used paired field and laboratory experiments to examine the individual and interactive impacts of agricultural land use and Hg contamination on hatch success and offspring phenotype in Chelydra serpentina. Of the 150 turtle nests found during this research, 84% were located in human-disturbed soils. Nest site characteristics were similar among nests found in Hg contaminated and reference areas. Agriculture and control nests did not differ in temperature at the time of nesting, but temperatures diverged as crops grew, with temperatures in nests in agricultural fields averaging 2.5 °C lower than control nests over the course of incubation. Similarly, despite no initial difference, nest moisture levels diverged throughout incubation and moisture averaged 107 kPa lower in agricultural than control soils throughout incubation. In my field and laboratory experiments, I found that in comparison to turtles from control incubation conditions (i.e., warmer), turtles incubated under agricultural thermal regimens (i.e., colder) took longer to hatch, hatched at smaller structural body sizes, lost more mass after hatching, had lower post-hatching structural growth rates, and were more likely to be male. Additionally, thermal conditions associated with agricultural land use interacted with high levels of mercury to impact hatching success and offspring sex ratios. My thesis research provides one of the first documentations of negative interactive effects of mercury pollution and habitat quality on early vertebrate development and highlights the importance of examining the combined influence of multiple global changes on biological systems. / Master of Science

In this work, we investigate the role of offspring hashtags on the semantic polarization of online discourse between the protest and counter-protest communities over time through the lens of the 2021 farmers' protest in India. Offspring hashtags are those that first appear alongside their more widely known "parent" hashtag (e.g., #WhyIDidntReport and #YesAllWomen are offspring hashtags that first co-appeared alongside their more famous and mainstream parent hashtag, #MeToo). The prominence of parent hashtags and their visible role in facilitating modern day protests have dominated scholarly efforts in understanding the socio-technical influence of social movement hashtags. By contrast, scholarship on the impact of the lesser-known offspring hashtags is rare and if any, typically examined through the lens of its primary parent tag. Our work aims to address this gap. In this research, we examine how the protest and counter-protest communities use offspring hashtags in their tweets to discuss and frame farmers - the key social group at the center of the farmers' protest (RQ1). Our findings reveal that both protests and counter-protests use offspring hashtags in a manner that further polarizes rather than bridges perspectives on core issues - focusing on themes that malign the other side (RQ2). We then measure and track how the semantic polarization in the use of the term "farmer" by the protest vs. counter-protest communities who use offspring hashtags evolves over time in relation to key protest events (RQ3). Finally, to empirically test and demonstrate whether and how the volume of offspring hashtags throughout the protest period influences semantic polarization trends between the protest and counter-protest discussion of farmers, we create a series of time-series models for causal inference. We use Granger-causality to test whether and how fluctuations in the volume of offspring hashtags significantly predict how the protest and counter-protest communities semantically diverge in how they discuss farmers over time (RQ4). By analyzing offspring hashtags, this work provides a detailed understanding of the nuanced themes and narratives that may be lost under parent hashtags, but significantly influence online discourse between the protest and counter-protest communities. / Master of Science / In this study, we explore how offspring hashtags, impact online conversations between people supporting and opposing the 2021 farmers' protest in India. Offspring hashtags are less popular hashtags that first appear with a more famous "parent" hashtag (for example, #WhyIDidntReport and #YesAllWomen alongside #MeToo). While researchers have extensively studied parent hashtags, the influence of offspring hashtags remains less explored. Our research looks at how protests and counter-protests use offspring hashtags to talk about farmers, who are at the center of the Indian farmers' protest. We found that both groups use offspring hashtags in a way that increases polarization rather than fostering understanding between opposing sides. This often leads to discussions that focus on attacking the other group. We also analyzed how the polarization in conversations about farmers evolved over time, in relation to key protest events and the use of offspring hashtags. To see if the number of offspring hashtags used during the protest affected polarization trends, we used statistical models and a method called Granger-causality. Our findings show that fluctuations in offspring hashtag volume significantly predict how protesters and counter-protesters diverge in their discussions about farmers over time. By examining offspring hashtags, we gain a deeper understanding of the subtle themes and stories that may be overlooked when focusing only on parent hashtags but play a crucial role in shaping online conversations between opposing groups.

Mitochondrial DNA (mtDNA) mutations have been widely observed to cause a variety of human diseases, especially late-onset neurodegenerative disorders. The prevalence of mitochondrial diseases caused by mtDNA mutation is approximately 1 in 5,000 of the population. There is no effective way to treat patients carrying pathogenic mtDNA mutation; therefore preventing transmission of mutant mtDNA became an important strategy. However, transmission of human mtDNA mutation is complicated by a large intergenerational random shift in heteroplasmy level causing uncertainty for genetic counseling. The aim of this dissertation is to gain insight into how human mtDNA heteroplasmy is inherited. By working closely with our experimental collaborators, the computational simulation of mouse embryogenesis has been developed in our lab using their measurements of mouse mtDNA copy number. This experimental-computational interplay shows that the variation of offspring heteroplasmy level has been largely generated by random partition of mtDNA molecules during pre- and early postimplantation development. By adapting a set of probability functions developed to describe the segregation of allele frequencies under a pure random drift process, we now can model mtDNA heteroplasmy distribution using parameters estimated from experimental data. The absence of an estimate of sampling error of mtDNA heteroplasmy variance may largely affect the biological interpretation drawn from this high-order statistic, thereby we have developed three different methods to estimate sampling error values for mtDNA heteroplasmy variance. Applying this error estimation to the comparison of mouse to human mtDNA heteroplasmy variance reveals the difference of the mitochondrial genetic bottleneck between these organisms. In humans, the mothers who carry a high proportion of m.3243A>G mutation tend to have fewer daughters than sons. This offspring gender bias has been revealed by applying basic statistical tests on the human clinical pedigrees carrying this mtDNA mutation. This gender bias may partially determine the mtDNA mutation level among female family members. In conclusion, the application of population genetic theory, statistical analysis, and computational simulation help us gain understanding of human mtDNA heteroplasmy inheritance. The results of these studies would be of benefit to both scientific research and clinical application. / Ph. D.

A redução no desenvolvimento muscular de filhotes cujas mães foram submetidas ao consumo de dietas baseadas no padrão ocidental pode ser, ao menos em parte, explicada pela resistência periférica à insulina, condição na qual a atividade de proteínas relacionadas à via de sinalização intracelular sensível a esse hormônio encontra-se reduzida. A regulação positiva dessa via resulta no aumento da atividade do Alvo da Rapamicina em Mamíferos (mTOR) que atua como efetor positivo da taxa de tradução de RNAm e, consequentemente, da síntese proteica. Estudos que avaliam a atividade dessa proteína frente ao consumo crônico de dietas hiperlipídicas são escassos e controversos e, até o momento, não são conhecidos trabalhos que avaliaram esses marcadores em animais neonatos ou desmamados, provenientes de mães alimentadas com dieta hiperlipídica gestacional e pós-gestacional. O presente estudo objetiva avaliar o efeito do consumo de uma dieta hiperlipídica por ratas adultas sobre a morfologia e sobre a expressão e a fosforilação das proteínas que compõem a via de sinalização intracelular do mTOR no músculo esquelético da prole em dois momentos: nascimento e desmame. Para isso, inicialmente, 39 ratas foram distribuídas em dois grupos, de acordo com a dieta oferecida: controle (n=19) e hiperlipídica (n=20). Após o nascimento, cerca de seis filhotes por mãe foram eutanasiados para coleta de amostras e análise dos marcadores investigados. Os filhotes selecionados para dar continuidade ao experimento foram dispostos junto às mães que, por sua vez, foram distribuídas em outros quatro grupos, segundo a dieta gestacional e pós-gestacional: CON/CON (n=8); CON/HL (n=9); HL/HL (n=8); HL/CON (n=7). Ao final da lactação, os filhotes foram eutanasiados e amostras foram coletadas para análise. Os resultados obtidos indicam que, em relação aos animais neonatos, há redução das concentrações séricas de leptina e de IGF-I e aumento da fosforilação da Akt e do mTOR musculares, em resposta ao consumo materno da dieta hiperlipídica. Por sua vez, nos animais lactentes, observamos influência da dieta hiperlipídica materna pós-gestacional sobre a promoção de fenótipo obesogênico, com concomitante redução do desenvolvimento muscular e da fosforilação de proteínas alvo do mTOR em estado pós-prandial. Com base nos resultados obtidos, concluímos que a dieta hiperlipídica materna afeta a atividade do mTOR, sendo, esse efeito, dependente da idade e da condição fisiológica dos animais. / The decrease in muscle development of offspring whose mothers consume a typical Western diet can be partly explained by the progression of peripheral insulin resistance, a condition in which the activity of proteins related to the intracellular signaling pathway sensitive to this hormone is reduced. The positive regulation of this pathway results in increased activity of the Mammalian Target of Rapamycin (mTOR) that acts as a positive regulator of the rate of mRNA translation and protein synthesis. Studies that assess the activity of this protein in response to chronic consumption of high fat diets are scarce and controversial and, to date, studies that evaluated these markers in the offspring of mothers fed a high fat diet during gestational and lactation are not known. This study aims to evaluate the effect of consuming a high fat diet for female adult rats in morphology and expression and phosphorylation of proteins that comprise the intracellular signaling pathway of mTOR in skeletal muscle of offspring in two stages: birth and weaning. Therefore, initially, 39 rats were divided into two groups, according to the available diet: control (n = 19) and diet (n = 20). After birth, around six pups per mother were killed for sample collection and analysis of the markers investigated. The pups selected to continue the experiment were placed with the mothers who, in turn, were divided into four groups according to gestational and post-gestational diets: CON/CON (n = 8), CON/HL (n = 9), HL/HL (n = 8), HL/CON (n = 7). At the end of lactation, the pups were euthanized and samples were collected for analysis. The results indicate that, for the newborn animals, there is a reduction of serum leptin and IGF-I concentrations and increased phosphorylation of Akt and mTOR in muscle in response to maternal consumption of high fat diet. In turn, we found that maternal high-fat diet during lactation promoted an obese phenotype in weaned animals, with concomitant reduction of muscle development and mTOR target proteins phosphorylation in the postprandial state. Based on these results, we conclude that maternal high-fat diet affects the activity of mTOR, depending on age and physiological condition of the animals.