Aesthetics and Tourism

The aim of this few comments is to link tourism to the desire for beauty that seems to be side by side with humankind since the very beginnings. Reflections are grounded on Benjamin ́s interpretation of Baudelaire, on Boorstin, MacCannel and Urry, as well as on my own field experience and intend to stimulate more research on the role played by aesthetics in tourism experience

Assessing the Influence of Health Policy and Population Mobility on COVID-19 Spread in Arkansas

The outbreak of COVID-19 has created a major crisis across the world since its start in 2019, and its influence on every realm of society is undeniable. Globally, more than 500 million cases have been recorded since March 2020, with almost 6 million deaths. In the wake of this crisis, many governments and health organizations have taken steps and precautions to mitigate its spread. These steps involve public mandates of information, reducing frequency of personal contact, and use of masks to minimize the risk of transmission. Current access to mobility data released from Google detailing population movements has provided a great opportunity to quantify the correlation between COVID-19 mandates and health policies on community traveling and COVID spread. The aim of this study is to examine the relationship between population mobility and the COVID pandemic, specifically focusing on the state of Arkansas. Three main types of mobility changes and various indicators of COVID spread were examined from available data ranging from March of 2020 to March of 2022. We employed various statistical methods including discontinued regression, causality tests, and mixed regression models to better understand how implemented COVID safety polices relate to a population’s aggregate mobility, and to estimate the subsequent correlation between population mobility and COVID-19 spread within counties in Arkansas

\u3cem\u3eRacism in Metropolitan Areas.\u3c/em\u3e Rik Pinxten and Ellen Preckler.

Book note for Rik Pinxten and Ellen Preckler, Racism in Metropolitan Areas. New York: Berghahn Books, 2006. $70.00 hardcover,$22.50 papercover

\u3cem\u3eNot Working: Latina Immigrants, Low-wage Jobs and the Failure of Welfare Reform.\u3cem\u3e Alejandra Marchevsky and Jeanne Theorharis.

Book note for Rik Pinxten and Ellen Preckler, Racism in Metropolitan Areas. New York: Berghahn Books, 2006. $70.00 hardcover,$22.50 papercover

Comparative analysis of hypothalamic damage caused by pediatric craniopharyngioma versus pediatric low grade gliomas

Numerous studies have suggested rapid weight gain following diagnosis and initial treatment of childhood craniopharyngioma (CP) due to the damage sustained by the hypothalamus. Hypothalamic lesions formed by the treatment of the tumor and/or by invasiveness of the tumor itself are known to cause intractable weight gain, known as hypothalamic obesity. In contrast, hypothalamic obesity manifested in pediatric low-grade glioma (PLGG) patients is not as prominently addressed in literature; likely due to the expansive set of histological tumor subtypes that makes generalization challenging. Specifically, there is a lack of analysis that examines the difference in treatment, endocrinopathies, and weight gain between CP and PLGG patients. The purpose of this study was to compare hypothalamic damage in subjects diagnosed with pediatric hypothalamic low-grade glioma versus subjects diagnosed with childhood craniopharyngioma. We hypothesized that CP patients will have a more rapid post diagnosis weight gain and a greater degree of obesity compared with PLGG patients due to the more invasive nature of the tumor and the aggressive surgical treatments involved. We performed a retrospective review of the clinical records of patients who received a diagnosis of childhood craniopharyngioma or pediatric low-grade glioma at Dana-Farber Cancer Institute between 1980 and 2009. We identified 45 patients, who met criteria for evaluation, 28 were previously diagnosed with childhood craniopharyngioma and 17 were diagnosed with hypothalamic pediatric low-grade glioma. We analyzed the impact of treatment, the presence of endocrinopathies, and weight gain after diagnosis. We concluded that there was no statistically significant difference in the rate or magnitude of post diagnosis weight gain, disproving our initial hypotheses

Etude des interactions bidirectionnelles entre le microbiote intestinal et les récepteurs aux xénobiotiques CAR et PXR

Le pregnane X receptor (PXR, NR1I2) et le récepteur constitutif aux androstanes (CAR, NR1I3) sont deux récepteurs nucléaires hépatiques et intestinaux qui régulent la transcription d'enzymes de détoxification des xénobiotiques. Des travaux antérieurs ont montré que l'expression des gènes cibles de CAR et PXR est significativement réduite dans le foie des souris axéniques. Dans ce projet de thèse, nous avions pour objectif de mieux comprendre les interactions bidirectionnelles entre le microbiote intestinal et ces xénosenseurs. Nous avons d'abord utilisé une approche pharmacologique chez les souris mâles WT vs Pxr-/- et comparé la signature transcriptomique des gènes régulés par PXR dans le foie lors de l'activation via le PCN. L'activation de PXR a augmenté l'accumulation de triglycérides hépatiques. Nous avons observé un chevauchement significatif entre les gènes régulés négativement lors de l'activation de PXR et une liste de gènes cibles de PPARδ induits par le jeûne. Parmi ceux-ci, nous avons identifié le facteur de croissance de fibroblastes 21 (Fgf21) comme un nouveau gène régulé par PXR. L'activation de PXR a aboli les taux plasmatiques de FGF21. Ces premiers résultats ont fourni une signature complète de l'activation de PXR dans le foie et ont identifié de nouveaux gènes cibles potentiellement impliqués dans les effets stéatogènes et pléiotropes de PXR. Ensuite, nous avons comparé la signature hépatique à la signature intestinale de l'activation pharmacologique de PXR, ce qui nous a permis d'identifier les gènes cibles communs de PXR dans ces 2 organes. Enfin, nous avons utilisé des souris Pxr+/+ et Pxr-/- littermate et supprimé le microbiote intestinal au moyen d'antibiotiques (ATB). En utilisant les gènes cibles de PXR identifiés précédemment, nous avons confirmé que les ATB réduisaient de manière significative l'activité de PXR dans le foie et l'iléon. Des analyses transcriptomiques hépatiques ont montré que les ATB diminuaient un nombre beaucoup plus élevé de gènes PXR-dépendants dans le foie des souris mâles que chez les femelles. Chez les mâles, l'axe microbiote intestinal-PXR contrôlait le métabolisme des xénobiotiques et le remodelage des lipides hépatiques. À l'inverse, le séquençage 16S et la métabolomique par RMN du contenu caecal ont révélé des différences subtiles mais significatives dans la composition du microbiote intestinal des souris Pxr-/- par rapport aux souris Pxr+/+, uniquement chez les mâles. Nos résultats démontrent donc que, dans le foie, PXR est un senseur majeur du microbiote intestinal qui contrôle les capacités de détoxication de l'hôte et le métabolisme des lipides de manière sexuellement dimorphique. Dans le dernier chapitre, nous avons étudié les interactions microbiote-CAR. Chez les souris Car+/+ et Car-/- littermates, la suppression du microbiote par les antibiotiques a diminué l'activité de CAR dans le foie et l'iléon des mâles, mais uniquement dans le foie des femelles. Dans le contenu caecal, le séquençage 16S et la metabolomique ont montré une différence significative dans la composition et l'activité métabolique du microbiote intestinal chez les souris Car+/+ vs Car-/- mâles, mais pas chez les femelles. Nous avons cherché les conséquences potentielles de cette dysbiose CAR dépendante et avons observé que la délétion de CAR augmentait l'accumulation de tissu adipeux chez les souris mâles à 37 semaines. Cependant, l'implication du microbiote CAR-dépendant dans ce phénotype reste à vérifier. Ainsi, nos résultats montrent pour la première fois que l'interaction CAR-microbiote est sexuellement dimorphique et pourrait contrôler le dépôt adipeux chez les souris mâles. Dans l'ensemble, nos résultats montrent que le dialogue entre le microbiote intestinal et les récepteurs aux xénobiotiques CAR et PXR est impliqué de façon sexuellement dimorphique dans le contrôle des capacités de détoxification de l'hôte, et joue un rôle dans l'homéostasie lipidique.The pregnane X receptor (PXR, NR1I2) and the constitutive androstane receptor (CAR, NR1I3) are two liver and intestine-enriched nuclear receptors that act as transcriptional regulators of enzymes critical for the detoxification of xenobiotics and endogenous metabolites. Previous works have shown that the expression of CAR and PXR target genes is significantly reduced in the liver of germ-free mice. In this PhD project, we aimed to gain insights into the bidirectional interactions between the gut microbiota and these xenosensors. We first used a pharmacological approach in WT vs Pxr-/- male mice and performed a transcriptomic comparison of the PXR-regulated genes in the liver upon activation via the rodent activator PCN. We confirmed that PXR activation increased liver triglycerideaccumulation and significantly regulated the expression of genes, mostly involved inxenobiotic metabolism. We also highlighted a significant overlap between the genes downregulated upon PXR activation and a list of fasting-induced PPARδ target genes. Among these, we identified the well-described PPARδ target fibroblast growth factor 21 (Fgf21) as a new PXR-regulated gene. PXR activation abolished plasmatic levels of FGF21. This first set of results provided a comprehensive signature of PXR activation in the liver and identified new PXR target genes that might be involved in the steatogenic and pleiotropic effects of PXR. Next, we compared the hepatic vs. intestinal signature of the pharmacological activation of PXR. This allowed us to unravel the strongest PXR target genes in both organs. Finally, we used Pxr+/+ and Pxr-/- littermate mice and suppressed the gut microbiota using antibiotics (ATB). Using the previously identified PXR targets, we confirmed that ATB significantly decreased Pxr activity in the liver and ileum. Liver transcriptomic analyses showed that ATB decreased a much higher number of PXR-dependent genes in the liver of male mice than in females. In males, this gut microbiota-PXR axis controlled xenobiotic metabolism and lipid remodelling. Conversely, 16S sequencing and 1H-NMR-based metabolic profiling of caecal content revealed subtle but significant differences in the gut microbiota composition of male Pxr-/- vs. Pxr+/+ mice, while no difference was observed in females. Our results therefore demonstrate that hepatic PXR is a major sensor of the gut microbiota that controls the host detoxifying capacities and lipid metabolism in a sexually dimorphic way. In the final chapter, we investigated the microbiota-CAR interactions. In Car+/+ and Car-/- littermate mice. Microbiota suppression by antibiotics decreased CAR activity in the liver and ileum of males but only in the liver of females. In caecal content, male-specific and CAR-dependant metabolites were also detected through 1H-NMR-based metabolomics. Furthermore, 16S sequencing confirmed a significant difference in gut microbiota composition of Car-/- vs Car+/+ male mice but not in females. We investigated the potential consequences of this sexually dimorphic CAR-dependent dysbiosis and observed that long-term Car deletion increased adipose tissue accumulation in male mice (at 37 weeks old). Whether the Car-dependent dysbiosis is responsible for this phenotype remains to be determined. In 37-week-old females, Car deletion induced a significant increase in spleen weight and a decrease in colon length, therefore suggesting a role for Car in systemic and intestinal inflammation. Thus, our result show for the first time that the CAR-gut microbiota interaction is sexually dimorphic and might control adipose deposition in male mice. Overall, our results shed new light into the crosstalk between the gut microbiota and the host's xenobiotic receptors CAR and PXR, demonstrating that this cross-talk might be involved in the control the host's hepatic lipid and xenobiotic metabolism