Regulation of Intestinal Lipid Storage and Mobilization

Dietary fat is an energy dense nutrient that also provides essential fatty acids and aids in the absorption of fat soluble vitamins. The process of dietary fat absorption regulates the amount and rate at which dietary fat enters circulation, and can therefore contribute to diseases such as obesity, diabetes and cardiovascular disease when it becomes dysregulated. Triacylglycerol (TAG), the major form of dietary fat, is efficiently absorbed (\u3e95%) even when high amounts of fat are consumed. The digestive products of dietary fat are taken up by enterocytes, the absorptive cells of the small intestine, and rapidly re-synthesized into TAG. This re-synthesized TAG can either be packed onto chylomicrons and secreted into circulation for delivery to peripheral tissues, or temporarily stored within cytoplasmic lipid droplets (CLDs). The objective of this dissertation is to investigate the regulation of enterocyte lipid stores and their contribution to dietary fat absorption. First, we determined differences in enterocyte CLD-associated proteins in genetic models with alterations in intestinal TAG synthesis. Acyl-CoA: diacylglycerol acyltransferase 1 (Dgat1) and Dgat2 catalyze the final, committed step of TAG synthesis. Mouse models with intestine-specific overexpression of Dgat1 (Dgat1Int) or Dgat2 (Dgat2Int), or a whole body Dgat1 deficiency (Dgat1-/-), have previously been shown to exhibit alterations in intestinal TAG storage and secretion. We isolated CLDs from enterocytes of these models after an acute dietary fat challenge and identified proteins present in the enterocyte CLD-enriched fraction using LC-MS/MS. We identified a total of 158 proteins, 53 of which were common to all four models (Dgat1Int, WT, Dgat2Int, and Dgat1-/- mice). In addition, 13% of the proteins identified are associated with lipid metabolism, and several of these lipid metabolism related proteins were differentially present among the models. This analysis has identified novel potential regulators of intestinal lipid storage and mobilization. We also assessed differences in enterocyte CLD morphology and protein composition in models resistant compared to susceptible to high fat diet-induced obesity (DIO). Whole body Dgat1-/- mice exhibit alterations in intestinal lipid metabolism that are thought to contribute to their resistance to DIO and insulin resistance. In the current study we found that in response to chronic high fat feeding Dgat1-/- enterocytes contain a greater number of larger sized CLDs compared to enterocytes from WT, diet-induced obese mice. In addition, we identified a total of 125 proteins in the enterocyte CLD-enriched fractions from these models, 52 of which were only identified in the Dgat1-/- model. Furthermore, a greater number of proteins associated with the mitochondria and fatty acid oxidation were identified in the enterocyte CLD fraction from Dgat1-/- mice, and this was accompanied by more alterations in enterocyte mitochondrial morphology in this model. Overall, this study increases knowledge about alterations in enterocyte CLD metabolism in Dgat1-/- mice that may be contributing to their beneficial DIO-resistant phenotype. Finally, we investigated the effects of oral nutrient exposure and ingestion on intestinal lipid stores in both humans and mice. Glucose ingestion was shown to mobilize lipid stored in the intestine from a previous high fat meal in humans. We observed a decrease in enterocyte CLD number and a greater number of smaller sized CLDs in response to glucose compared to water ingestion. In addition, we identified a total of 2919 proteins present within human duodenal biopsy tissues in response to this dietary challenge, 134 of which were differentially present in response to glucose compared to water ingestion. Consistent with these human studies, we found that glucose compared to water ingestion (but not oral exposure) also decreases intestinal lipid stores in mice. Previous studies in humans have shown that sham feeding of fat and oral glucose ingestion induce a peak in plasma CM-TAG levels, however no detectable differences in plasma TAG levels were observed in mice in response to an oral fatty acid or glucose exposure, or to glucose ingestion in the present studies. This work confirms and expands upon previous work in humans by identifying the specific enterocyte lipid pools mobilized by glucose ingestion, as well as identifying glucose regulated proteins in the small intestine that have the potential to contribute to the observed glucose stimulated lipid mobilization. Taken together, this work identifies novel potential regulators of intestinal lipid storage and mobilization. Further investigation into their contributions to dietary fat absorption will help to provide novel dietary and therapeutic strategies for the management of obesity, hypertriglyceridemia, and related metabolic diseases

Consumers\u27 Cooperation in the Early Twentieth Century: An Analysis of Race, Class and Consumption

Consumers’ cooperatives are commonly associated with members of the middle class who use their buying power to support local economies and encourage the equitable production, distribution and consumption of food. However, consumers’ cooperation was initially introduced to the United States in the mid-nineteenth century via labor organizations. Consumers’ cooperation continued to develop as a form of consumer activism during the Progressive Era as the consumer became a more influential figure in American society. One faction of the consumers’ cooperative movement, which sought to transfer power to the working class, was unique compared to consumer movements of the time which were typically led by middle-class reformers who professed to be advocating on behalf of the poor and working class. This movement was also unique in the sense that it was a largely a white working-class movement that did not define class and class conflict in the relations of production, but instead in the relations of distribution/consumption (a definition of class that did not gain meaningful traction in the United States until the post-industrial era). Contemporaneously, another faction of the consumers’ cooperative movement was characterized by black American membership and an explicit and implicit promotion of black self-segregation. The existence of a black consumers’ cooperative movement has largely been ignored or, when acknowledged, treated as part of a single consumers’ cooperative movement. My dissertation treats consumers’ cooperation in the early twentieth century as two distinct movements - one class-based, one race-based - and specifically analyzes both as radical economic development strategies, not as consumer activist reform campaigns more common to the era. The lack of attention paid to segregated black consumers’ cooperation in scholarly literature has had the unintended consequence of limiting sociologists’ analyses of W.E.B. Du Bois. Du Bois, an early and enthusiastic advocate of black consumers’ cooperation, was a leader of the movement and wrote extensively and consistently on black consumers’ cooperation as a foundation for economic development and salvation for black Americans. His advocacy of consumers’ cooperation played a central role in his eventual promotion of black self-segregation. My findings: challenge the dominant narrative of class transformation in the United States and contribute to a refined understanding of historical and contemporary conceptions and locations of class; complicate the common analysis of black consumer movements as integrationist and expand the literature on black self-segregationist movements; and add significantly to the resurgence in the study of W.E.B. Du Bois, a central figure in the history of sociology, as both a scholar and activist

The evolution of representation in architecture

This paper proposes an overview on the relation between representation, technology and architecture methodologies. Focusing on disposable digital tools, it reaches the new tools of virtual immersive 3D architectural environments. It also addresses the concepts of operative 3D, augmented reality and robotic manufacturing, thus introducing a system of digital tools that enables users to step inside a 3D virtual reality environment, built as a virtual building prototype, and to use all data instructions directly with the construction industry. This paper questions therefore the traditional processes and perceptions in architecture and draw present and future advanced state-of-the-arts methodologies. As a result, future and tradition in architectural design methods are challenged. Recognizing the permanent tensions between traditional and innovative processes, possible methodological changes are put in perspective, namely the fields of technical representation, building construction and design processes.info:eu-repo/semantics/publishedVersio

Árgon-plasma no tratamento de leiomioma benigno metastizante pulmonar: um caso clínico

AbstractBenign metastasizing leiomyomas of the lung are rare smooth muscle cells tumours. We report the case of a 48 year-old female who was evaluated due to persistent cough, progressive dyspnoea and constitutional symptoms. Chest computed tomography revealed a left endobronchial mass, multiple parenchyma nodules and a pleural effusion. Bronchial biopsy histological features were consistent with benign metastasizing leiomyoma. The patient was successfully treated with argon-plasma and mechanical debulking. There was no disease relapse in the last four years

Five-membered iminocyclitol a-glucosidase inhibitors: Synthetic,biological screening and in silico studies

The design and synthesis of a small library of pyrrolidine iminocyclitol inhibitors with a structural similarity to 1,4-dideoxy-1,4-imino-D-arabitol (DAB-1) is reported. This library was specifically designed to gain a better insight into the mechanism of inhibition of glycosidases by polyhydroxylated pyrrolidines or iminocyclitols. Pyrrolidine-3,4-diol 15a and pyrrolidine-3,4-diol diacetate 15b had emerged as the most potent a-glucosidase inhibitors in the series. Docking studies performed with an homology model of a-glucosidase disclosed binding poses for compounds 15a, 15b, 16a, and 16a0 occupying the same region as the NH group of the terminal ring of acarbose and suggest a closer and stronger binding of compound 15a and 15b with the enzyme active site residues. Our studies indicate that 2 or 5-hydroxyl substituents appear to be vital for high inhibitory activity

Admission for Imported Malaria in Children, in Two Hospitals of Lisbon Urban Area

Introdução: Apesar de em Portugal não haver malária endógena,a crescente mobilidade das populações e os laços históricos com África possibilitam a importação de casos para o nosso país. O presente estudo pretende contribuir para melhorar o conhecimento epidemiológico e clínico da malária importada na região de Lisboa. Métodos: Realizou-se um estudo descritivo das crianças com malária, internadas em dois hospitais da Grande Lisboa, durante um período de seis anos (1999-2004). Resultados: Foram identificados 134 casos, sendo a mediana das idades de sete anos. A maioria (93,3%) era de origem africana e referia estadia em região endémica (90%). O Plasmodium falciparum foi o agente etiológico mais frequente (73%). A febre foi a manifestação clínica mais frequente, seguida de manifestações gastrointestinais e cefaleias. Ocorreram complicações em 42% dos doentes, sendo a trombocitopenia (19,4%) e a anemia grave (9%) as mais frequentes. A halofantrina e o quinino foram os anti-maláricos mais usados. Conclusões: A malária importada é uma patologia relativamente comum na Grande Lisboa e, dada a inespecificidade do quadro clínico, todas as crianças febris ou doentes com estadia recente num país endémico devem ser rastreadas para esta entidade

Strengthening governance arrangements for small city and town sanitation in Sumatra, Indonesia – a selection of key themes for local governments and policy makers. A Briefing Paper.

This project brief summarises key themes from research that investigated local government governance and institutional arrangements for sanitation (wastewater) planning, budgeting and implementation in small cities and towns in Sumatra, Indonesia

Translation and cross-cultural adaption of the motor behavior checklist (MBC) into Brazilian Portuguese

Introduction:There are only a few instruments available to assess behavioral problems in school-age children based on reports of physical education teachers. The Motor Behavior Checklist (MBC; Efstratopoulou, Janssen, Simons, 2012) was designed to be completed by this professional in free play-situations or during physical education classes to rate students’ motor-related behavior using 5-point Likert scales. The MBC comprises 59 items distributed into two broadband factors (externalizing and internalizing) and seven behavior problem scales: rule breaking, hyperactivity/impulsivity, lack of attention, low energy, stereotyped behaviors, lack of social interaction, and lack of self-regulation. The objective of this study was to describe the translation and cross-cultural adaptation processes of the MBC into Brazilian Portuguese. Method: The following procedures were conducted: forward translation of the original instrument, production of a synthesized version, back-translation, literal and semantic comparison, back-translator’s evaluation of divergent items, synthesized version with back-translator’s suggestions, clarity assessment of the synthesized version by professionals (physical education teachers), focus group to assess clarity indicators of the instrument, evaluation of adjustments by the author of the instrument, and production of the final version. Results: The results indicated a satisfactory level of agreement between the original and the back-translated versions, with 68% of exact equivalence between the translated items and 16% of terms requiring minor adjustments. In the draft version, 84% of the items were evaluated as clear by physical education teachers. Conclusion:Future studies should be conducted to assess the psychometric properties of the Brazilian Portuguese version of the MBC

Issue 2 - “Update on adverse respiratory effects of indoor air pollution” Part 1): Indoor air pollution and respiratory diseases: A general update and a Portuguese perspective

Objective To quantify the impact of different air pollutants on respiratory health based on robust estimates based on international data and to summarise the evidence of associations between indoor exposure to those pollutants and respiratory morbidity in the Portuguese population. Results Several systematic reviews and meta-analyses (MA) at the world level demonstrate the impact of indoor air quality on respiratory health, with indoor particulate matter and gasses exerting a significant effect on the airways. Volatile organic compounds (VOC) have been related to asthma and lung cancer. However, only meta-analyses on biomass use allowed documentation of long-term respiratory effects. While early publications concerning Portuguese-based populations mainly focused on indoor exposure to environmental tobacco smoke, later studies relocated the attention to relevant exposure environments, such as day care buildings, schools, residences and nursing homes. Looking at the pooled effects from the reviewed studies, high levels of carbon dioxide and particulate matter in Portuguese buildings were significantly associated with asthma and wheezing, with VOC and fungi showing a similar effect in some instances. Conclusions Despite the significant reduction of indoor air pollution effects after the 2008 indoor smoking prohibition in public buildings, studies show that several indoor air parameters are still significantly associated with respiratory health in Portugal. The country shares the worldwide necessity of standardisation of methods and contextual data to increase the reach of epidemiological studies on household air pollution, allowing a weighted evaluation of interventions and policies focused on reducing the associated respiratory morbidity