Examining the Regulation of Cell Division by the Spindle Assembly Checkpoint

Accurate chromosome segregation during cell division is essential for the maintenance of a cell’s genomic stability. The molecular surveillance mechanism called the spindle assembly checkpoint (SAC) inhibits chromosome segregation before all chromosomes are correctly attached (bi-oriented) on the microtubule spindle to prevent segregation errors that may lead to chromosomal instability and cell death. In this thesis, I have developed and used tools to examine the roles of different checkpoint proteins in the mechanism of SAC signaling. In the first part of the thesis, I manipulate the localization of the checkpoint protein Mad1 and show that its constitutive presence at the kinetochore is sufficient to induce checkpoint arrest. Being able to uncouple checkpoint signaling from chromosome biorientation, I use the system as a tool to examine the roles of checkpoint kinases in SAC signaling downstream of kinetochore recruitment of Mad1. I show that the kinases Mps1 and Aurora B are necessary for the maintenance of checkpoint arrest, independently of their other upstream checkpoint functions. I also show that localization of Mad1 at other chromosomal locations is not per se sufficient to induce checkpoint arrest. In the second part of the thesis, I collaborate in the development of a tool for the study of the protein dynein, a microtubule-associated motor with mitotic regulatory roles in spindle assembly, kinetochore-microtubule interactions and SAC silencing, as well as a variety of cargo-translocation roles in interphase. I examine the effects of the small molecule ciliobrevin in mitotic cells and help validate it as the first specific dynein inhibitor. Although I determine that its effects on the microtubule spindle will preclude its use in checkpoint silencing studies, ciliobrevin will still be a powerful tool for other biochemical, structural and cellular investigations of dynein function

Medicalitzar i mercantilitzar l’obesitat

A la nostra societat cos i salut han esdevingut una preocupació fonamental.El valor atorgat a la primesa i la consideració de l’obesitat com a patologia constitueixenuna poderosa motivació contra l’excés de pes. La insistència des de la biomedicinaen la necessitat de controlar el pes corporal per motius de salut legitima la ideade salut en relació amb la pèrdua de pes. Un ampli sector econòmic s’estructura alvoltant del binomi bellesa-salut i, sota l’aparença de vida saludable, promou el culteal cos per raons d’estètica. Aquest article planteja el paper que la medicalització i lamercantilització de l’obesitat tenen en la problematització del pes corporal

"In vitro" evaluation of some properties in spore former bacteria isolated from calves faeces

Aims: To isolate and evaluate spore-former bacteria for being used as probiotic additives in animal nutrition by their technological features. Study Design: The study was experimental, by using calves’ faeces for spore-forming identification and further evaluation of their “in vitro” probiotic-related properties. Place and Duration of Study: Laboratory of Preventive Microbiology, Centro de Referencia para Lactobacilos (CERELA-CONICET), between June 2013 and November 2013. Methodology: In this work, some Bacillus strains were isolated from calves’ faeces and evaluated for their “in vitro” beneficial characteristics: Surface properties, biosurfactant and emulsification production, and inhibition of pathogens. The antibiotic sensibility was also assayed. Results: Two Bacillus strains were selected, identified by phenotypic and molecular techniques as Bacillus subtilis strains M14 and M12. Spores resulted to be more hydrophobic than vegetative cells. The M14 strain showed biosurfactant and emulsifying properties. Inhibition assays against pathogenic bacteria indicated they inhibit gram-positive microorganisms. The antibiotic susceptibility showed that the two strains were sensitive to the antibiotics assayed, except Bacillus M12 that was resistant to Kanamycin. Conclusion: The results indicate these strains can be further studied for their inclusion in the design of a probiotic product for newborn calves.Fil: Maldonado, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Silva de Ruíz, Clara. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Nader, Maria Elena Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

A Student\u27s Experiences and Observations in Public Health Nutrition with the Florida State Board of Health

This report is based upon student\u27s experiences and observations during a 7 weeks\u27 period of field training in Public Health Nutrition with the Florida State Board of Health. Six weeks were spent with the Regional Nutrition Consultant in Saint Petersburg, and one week was spent with the local nutritionist in the Hillsborough County Health Department in Tampa. Because it was impossible to grasp the scope of a state, district, and local program in a 7 weeks\u27 period, the information given in this report is necessarily limited. The main objectives of the field training were: (1) to give the student an understanding of the organization, functions, and programs of an official health agency; (2) to learn how nutrition is integrated into the total public health program; (3) to become aware of the problems and needs in public health; (4) to gain an understanding of the work of a nutrition consultant in conducting the nutrition program as related to public health needs; and (5) to help the student realize or become aware of the challenges in the field of Public Health Nutrition. The over-all goal of the field experiences was to implement the student\u27s academic training and to broaden her concept of Public Health Nutrition. To help the student accomplish these objectives, the state and district nutritionists planned a program of varied experiences. Several activities were planned with the Pinellas County Health Department in Saint Petersburg. These activities were necessarily limited because the office of the regional nutritionist is located in the Mound Park Hospital. The student had opportunity to work with some of the local health personnel while working on a special assigned project. Other experiences included field visits to small health departments, voluntary agencies, and school lunchrooms. The student had conferences with the Director of Nutrition Services and observed the local and regional nutritionists teaching nutrition classes

Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells

Atherosclerosis is a widespread disease that often leads to serious conditions such as myocardial infarction and stroke. Chronic inflammation plays an overarching role in its pathophysiology, driving initiation and progression of atherosclerosis in humans and animal models. IL-1β is a potent inflammatory cytokine implicated in atherogenesis and other vascular diseases. However, control of its activation and release has been predominantly studied in macrophages, with scant data on whether vascular smooth muscle cells (VSMCs) can release IL-1β. I investigated the expression, activation and release of IL-1β from primary human VSMCs. VSMCs expressed caspase-1, -4, and -8 under basal conditions, but not caspase-5. Stimulation of VSMCs with IL-1α and/or LPS caused rapid processing of IL-1β to the mature form, which could be detected by Western and with a mature IL-1β-specific ELISA. Although IL-1β production and cleavage was dependent on NF-κβ activation, neither caspase or NLRP3 inflammasome inhibitors prevented generation of mature IL-1β, suggesting caspase- and NLRP3-independent processing. Instead, production of mature IL-1β was blocked by the serin protease inhibitor dichloroisocoumarin, with cathepsin G the most likely enzyme responsible for pro-IL-1β activation. Interestingly, mature IL-1β was never detected in the conditioned media and instead accumulated to high levels inside VSMCs. VSMCs expressed the pore-forming protein Gasdermin D, and the active form of Gasdermin D permeabilised VSMCs, yet mature IL-1β was still not released. Finally, mature IL-1β extracted from VSMCs has 13-fold lower activity than equal amounts of mature IL-1β from Thp1 cells, however the existence of a binding partner or inhibitor of IL-1β is unlikely the cause of this phenomenon. In conclusion, the work presented in this thesis suggests that VSMCs have a novel mechanism that specifically prevents the release of active IL-1β, and that perturbation of this could potentially contribute to vascular inflammation and atherogenesis.My PhD was generously funded by Darwin College and the Venezuelan National Academy of Medicine (Darwin College - Vargas Scholarship)

ICT-related transformations in Latin American metropolises

The use and application of ICT within and between cities is resulting in significant urban transformations, making cities more connected as well as more complex. A sub-discipline of urban studies - urban ICT studies - has recently emerged to explore, analyse and theorise how the technological advances are transforming urban forms, urban processes and the perceptions of urban life. ICT-related transformations in cities of the developing world, however, have not received enough academic attention until now. This book makes a contribution to the field of urban ICT studies in cities of the South, by exploring the ICT-related transformations in the Latin American urban scene. Based on Gabriel Dupuy’s notion of ‘urbanism of networks’, this explorative research identifies and analyses the recent transformations at three levels: the ICT infrastructure networks, the networks of production and consumption of ICTs in the local urban economy, and the diffusion of digital connectivity in everyday life. The book also presents the situation of digital connectivity in Buenos Aires and Lima, selected as case-studies because singular ICT-related processes are occurring in these two large metropolises. Besides from identifying the urban main trends at the different levels, the results have been also useful to spell out the main trends regarding urban functioning and the urban form, as well as the new problems and new opportunities that the introduction and development of ICTs bring to Latin American cities. The main findings point out that Latin American metropolises have great assets at the infrastructural level as main nodes of the ICT backbones infrastructures. However, there is a profound contradiction between the ICT-related developments occurring in the urban economies, and the social and cultural life of the cities. The low performance of the Latin American metropolises regarding their integration in the global economy and the production of science and technology are in stark contrast with the eagerness of Latin Americans to be connected and to be able to participate as citizens in the network society. These contradiction constitute the largest problem of the future of the metropolises

Trace-metaldynamics in response of increase CO₂ and iron availability in a coastal mesocosm experiment

A mesocosm experiment was performed in the Raunefjord (Norway) to study changes in dissolved Cu (dCu) and Fe (dFe), and in the elemental composition of particles during an Emiliania huxleyi dominated bloom. The CO2 treatments consisted of present (LC; 390 ppmV) and predicted levels (HC; 900 ppmV) and iron conditions were created with the addition of the siderophore desferoxamine B (DFB). Our results showed the DFB addition enhanced the solubility of Fe in this fjord environment. Initially, dFe was comparable among treatments but after the addition, the HC and/or +DFB treatments presented higher levels and finally, the only ones maintaining high dFe were the +DFB treatments. Unlike dCu presented indistinguishable levels in all mesocosms over time. Particulate metals were normalised to P and Al to evaluate the relative influence of biotic and abiotic sources. The Fe:P ratios decreased with time and compared to published phytoplankton ratios suggest Fe storage. On the other hand, Fe:Al ratios were relatively closer to the crustal ratios suggesting that the abiotic source was more important for this metal. Trends for other metals will be discussed.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The Judiciary in Political Transitions: The Critical Role of U.S. Constitutionalism in Latin America

This paper proposes a theory that explains how political transitions deal with incumbent judiciaries. We argue that a new political regime compares the benefit of reshaping the judiciary with loyal appointees against the political and economic costs of directly interfering, including the cost of international reputation. There are several forms of interventionism including court packing, court purging, and violence against the judiciary. We discuss political transitions in Europe and Latin American civil law jurisdictions through the lens of our theory. We argue that American constitutional influence plays a critical role. In addition, we provide a detailed analysis of the recent case of Venezuela, a process that began in 1999. The Venezuelan case verifies two conditions identified by our model: weaker forms of formalism and an institution\u27s lack of prestige, and, in particular, the justices of the Supreme Court of Justice. These factors explain the strategic choices of Venezuela\u27s current President, Hugo Chavez

The Judiciary in Political Transitions: The Critical Role of U.S. Constitutionalism in Latin America

This paper proposes a theory that explains how political transitions deal with incumbent judiciaries. We argue that a new political regime compares the benefit of reshaping the judiciary with loyal appointees against the political and economic costs of directly interfering, including the cost of international reputation. There are several forms of interventionism including court packing, court purging, and violence against the judiciary. We discuss political transitions in Europe and Latin American civil law jurisdictions through the lens of our theory. We argue that American constitutional influence plays a critical role. In addition, we provide a detailed analysis of the recent case of Venezuela, a process that began in 1999. The Venezuelan case verifies two conditions identified by our model: weaker forms of formalism and an institution\u27s lack of prestige, and, in particular, the justices of the Supreme Court of Justice. These factors explain the strategic choices of Venezuela\u27s current President, Hugo Chavez