Novel functions of the cohesin accessory factor dPDS5 uncover a new meiotic checkpoint

Dissertation presented to obtain the Ph.D degree in Biology.

Multivariate analysis applied to clinical analysis data

Dissertação para obtenção do Grau de Mestre em Engenharia e Gestão Industrial

Preliminary study into the landing behaviour on the human body of morning-biting mosquitoes in Atlantic forest in the State of Santa Catarina (Diptera: Culicidae)

Mosquitoes (22 species) (0.5%) and Runchomyia reversa (5%) biting humans in the morning in Florianópolis, State of Santa Catarina, were significantly more common below than above waist and all Wyeomyia incaudata were collected below the waist. Short trousers are not recommended, unless using repellents.

Coordinating development: uncovering the mechanisms that coordinate organ growth and patterning with the development of the whole body

Organisms produce correctly patterned structures across a wide range of organ and body sizes. Despite considerable work revealing the mechanisms that regulate the growth and patterning of organs, those responsible for coordinating organ development with whole-body development are still largely unknown.(...)

Development and efficiency optimizing of the human body energy converters

Nowadays it is known that the human body is continuous source of many types of energy and the devices used for collecting energy taken from the environment also have the required capabilities for the collection of the energy produced by the Human body (HB), but very limited and with very low efficiency. Low power and high yield converters are particularly needed in these cases of collecting energy from human activity and its movements due to the small amount of energy generated this way. But this situation can be improved. Enhancing or focusing the human movements by using mechanical amplifiers applied to the piezoelectric element. By doing so the input of energy in the element increases. As such increasing its output, therefore producing more energy.

Hematopoiesis in the Drosophila larva: beyond the lymph gland

All coelomate animals possess a population of cells that do not make part of an organ and instead freely flow inside the body cavity. These cells, termed hemocytes (in invertebrates) or blood cells (in vertebrates), are involved in varied functions including immune response, clearance of apoptotic cells and distribution of nutrient and gases (Grigorian & Hartenstein 2013).(...)

A cor como abrigo: a arquitectura como cuidado

A presente tese intitulada “A cor como abrigo: a arquitectura como cuidado” tem por objectivo fortalecer a ligação entre a “Teoria das Cores” de Goethe e a arquitectura. Para isso a nossa estratégia foi recuperar os conceitos de espaço e corpo. Ambos começam por ser tomados como realidades físicas mas pouco a pouco vai-se mostrando que tal coisa como uma abordagem ‘puramente física’ do espaço e do corpo não é possível - talvez porque não exista. Mesmo a medicina (ao contrario do que possamos pensar primeiro) é uma ciência que não só reconhece o carácter diáfano do corpo como diariamente luta para ir além de uma concepção do corpo enquanto coisa física por perceber que o corpo é determinado por formas e funções mas sobretudo como tomado por forças. Um exemplo extremo desta interacção entre espaço e corpo (ligados através da arquitectura), onde o carácter diáfano de ambos ganha evidência, é na arquitectura de hospitais, que abordamos por último: “o que é um espaço vivido que tem por principal função restaurar o corpo do seu estado de doença?” As referencias principais são J.W. Goethe, Ludwig Wittgenstein, Edmund Husserl, Gilles Deleuze, Christian Norberg- Schulz, Frank Lloyd Wright and Tadao Ando. *********************************************************************This PhD research thesis titled: "Colour as shelter: architecture as care" has as its main goal to strengthen an existing relation between Goethe's Theory of Colours and Architecture. In order to do that our strategy was to use space and body as guiding concepts. Both start as being considered from a pure physical point of view but as our theme develops we see that a “pure physical point of view” concerning space and body it is not possible – perhaps because it does not exist. Medicine (unlike we may think at first) it is a science that not only acknowledges the diaphanous character of the body as daily, tries to go beyond the conception of body as physical thing understanding that the body is determined by forms and functions but mostly taken by forces. An extreme example of the interaction between space and body (linked through architecture), where the diaphanous character of both is evident, is Healthcare architecture: "what is a lived space that has as main function to restore the body of its illness"? Main references are: J.W. Goethe, Ludwig Wittgenstein, Edmund Husserl, Gilles Deleuze, Christian Norberg-Schulz, Frank Lloyd Wright and Tadao Ando.

Is an increased body mass index associated with a risk of cutaneous leishmaniasis?

All adults (n = 334) living in Brejo do Mutambal, an endemic area for cutaneous leishmaniasis, were included in this study. Contrary to our initial hypothesis, it was observed that men (23.7 ± 3.2 vs. 22.1 ± 2.6 kg/m²) and women (24.1 ± 4.7 vs. 22.5 ± 3.4 kg/m²) with cutaneous leishmaniasis presented higher body mass index than the controls.

Untitled: Figurations of memory

The next pages will describe my experience and results of making connections between cognitive sciences and art; the transformations of my memories being the object of study and motivation for this process of self-discovery. The human body reacts according to innumerable neural functions and external stimuli. Neurons respond to the evocation of experienced events, building virtual images, map-like constellations sometimes fulfilled by imagination, desires or knowledge promoting in this way their constant reshaping. This document offers an insight into my recollections as matter. As matter these recollections take on different states and I hope to give you a better sense of my personal voice using my experience with glass to explore this transformation and accompanying my journey with lectures and scientific readings about the mind functions.

Manipulation of host cell functions by Salmonella: the role of the bacterial effector protein SteA

Salmonella enterica serovars are Gram-negative facultative intracellular bacterial pathogens that infect a wide variety of animals. Salmonella infections are common in humans, causing usually typhoid fever and gastrointestinal diseases. Salmonella enterica serovar Typhimurium (S. Typhimurium), which is a leading cause of human gastroenteritis, has been extensively used to study the molecular pathogenesis of Salmonella, because of the availability of sophisticated genetic tools, and of suitable animal and tissue culture models mimicking different aspects of Salmonella infections.(...)

L'Oreal acquisition policy: The Body Shop case study

The Work Project I present focuses on the analysis of L’Oréal acquisition policy, trying to outline if the M&A deals it has led over the last 14 years have succeeded in creating value. By replicating the model proposed by Todd Hazelkorn, Marc Zenner and Anil Shivdasani in their paper “Creating Value with Mergers and Acquisitions”, I analyzed the 29 M&A deals that L’Oréal has led worldwide, understanding the common factors able to explain the success of such transactions. Further, I focused on The Body Shop case study, a highly criticized and controversial acquisition that has proved to be profitable and able to create value.

Modulation of electrical stimulation applied to human physiology and clinical diagnostic

The use, manipulation and application of electrical currents, as a controlled interference mechanism in the human body system, is currently a strong source of motivation to researchers in areas such as clinical, sports, neuroscience, amongst others. In electrical stimulation (ES), the current applied to tissue is traditionally controlled concerning stimulation amplitude, frequency and pulse-width. The main drawbacks of the transcutaneous ES are the rapid fatigue induction and the high discomfort induced by the non-selective activation of nervous fibers. There are, however, electrophysiological parameters whose response, like the response to different stimulation waveforms, polarity or a personalized charge control, is still unknown. The study of the following questions is of great importance: What is the physiological effect of the electric pulse parametrization concerning charge, waveform and polarity? Does the effect change with the clinical condition of the subjects? The parametrization influence on muscle recruitment can retard fatigue onset? Can parametrization enable fiber selectivity, optimizing the motor fibers recruitment rather than the nervous fibers, reducing contraction discomfort? Current hardware solutions lack flexibility at the level of stimulation control and physiological response assessment. To answer these questions, a miniaturized, portable and wireless controlled device with ES functions and full integration with a generic biosignals acquisition platform has been created. Hardware was also developed to provide complete freedom for controlling the applied current with respect to the waveform, polarity, frequency, amplitude, pulse-width and duration. The impact of the methodologies developed is successfully applied and evaluated in the contexts of fundamental electrophysiology, psycho-motor rehabilitation and neuromuscular disorders diagnosis. This PhD project was carried out in the Physics Department of Faculty of Sciences and Technology (FCT-UNL), in straight collaboration with PLUX - Wireless Biosignals S.A. company and co-funded by the Foundation for Science and Technology.

Involvement and interactions of different immune cells and their cytokines in human visceral leishmaniasis

Visceral leishmaniasis (VL) or kala-azar, a disseminated infection of the lymphoreticular system of the body, is marked by severe defect in immune system of the host. Successful cure of VL depends on the immune status of the host in combination with the effects of the antileishmanial drugs. The rationale approach towards eradication of this disease would be to potentiate the immune functioning of the host in addition to parasite killing. This review deals with different aspects of adaptive and innate immune responses and explores their role in protection or pathogenesis of VL. IL-10 has emerged as the principal cytokine responsible for disease pathogenesis, although evidences regarding its source during active VL remain inconclusive. On the other hand, IFNγ, under the influence of IL-12, is mostly correlated with healing of the disease. Chemokines are important in mounting cell-mediated immune response as they can prevent parasite invasion in association with cytokines. Different types of T cells like CD4, CD8 and NK T cells also contribute to the immunology of this disease. In spite of conflicting reports, the role of regulatory T cells in VL pathogenesis is important. Recently discovered Th17 subset and its different members have been reported to perform diverse functions in the course of VL and leishmaniasis as a whole. Innate immune responses, depending on the cell types, are essential in early parasite detection and subsequent development of an efficient NK cell response. Immunotherapy targeting IL-10 could be looked upon as an interesting option for the treatment of VL.

Knowledge management framework based on brain models and human physiology

The life of humans and most living beings depend on sensation and perception for the best assessment of the surrounding world. Sensorial organs acquire a variety of stimuli that are interpreted and integrated in our brain for immediate use or stored in memory for later recall. Among the reasoning aspects, a person has to decide what to do with available information. Emotions are classifiers of collected information, assigning a personal meaning to objects, events and individuals, making part of our own identity. Emotions play a decisive role in cognitive processes as reasoning, decision and memory by assigning relevance to collected information. The access to pervasive computing devices, empowered by the ability to sense and perceive the world, provides new forms of acquiring and integrating information. But prior to data assessment on its usefulness, systems must capture and ensure that data is properly managed for diverse possible goals. Portable and wearable devices are now able to gather and store information, from the environment and from our body, using cloud based services and Internet connections. Systems limitations in handling sensorial data, compared with our sensorial capabilities constitute an identified problem. Another problem is the lack of interoperability between humans and devices, as they do not properly understand human’s emotional states and human needs. Addressing those problems is a motivation for the present research work. The mission hereby assumed is to include sensorial and physiological data into a Framework that will be able to manage collected data towards human cognitive functions, supported by a new data model. By learning from selected human functional and behavioural models and reasoning over collected data, the Framework aims at providing evaluation on a person’s emotional state, for empowering human centric applications, along with the capability of storing episodic information on a person’s life with physiologic indicators on emotional states to be used by new generation applications.

Unravelling the role of alpha 2,6 sialic acid on mouse dentritic cells functions

RESUMO: As células dendríticas (CDs) são fundamentais na imunomodulação e iniciação de respostas imunes adaptativas, enquanto os ácidos siálicos (Sias) são potenciais imunomoduladores. Estas células expressam níveis elevados da sialiltransferase ST6Gal-1, que transfere Sias para a posição terminal de oligossacáridos. De facto, a maturação de CDs está associada a uma diminuição da sialilação na sua superfície celular. Apesar de ter função biológica desconhecida, a forma solúvel, extracelular de ST6Gal-1 aumenta em cancros e inflamação. Ainda assim, esta foi recentemente identificada como moduladora da hematopoiese. Considerando o importante papel das CDs na iniciação de respostas anticancerígenas, uma ligação entre a sialilação extrínseca induzida por ST6Gal-1 extracelular e o seu papel na modulação de CDs deve ser identificada. Neste trabalho hipotetizou-se que a sialilação α2,6 extrínseca de CDs diminui o seu perfil de maturação mediante ativação por lipopolissacarídeo (LPS). O objetivo principal foi sialilar extrinsecamente em α2,6 CDs da medula óssea de murganhos, avaliando os seus perfis de maturação e de libertação de citocinas, após estimulação com LPS (por Citometria de Fluxo e ELISA, respetivamente). Ao contrário da hipótese, o perfil celular não foi modulado, usando várias abordagens. Por outro lado, a consequência da falta de α2,6 Sias na maturação de CDs foi avaliada analisando: 1) CDs da medula óssea de murganhos tratadas com sialidase, 2) CDs da medula óssea e 3) CDs das vias aéreas, ambas de murganhos deficientes em ST6Gal-1, comparando com a estirpe selvagem. Estes resultados sugerem que a perta total de α2,6 Sias se relaciona com o aumento da expressão do complexo de histocompatibilidade principal de classe II. Apesar de controverso, é provável existirem mecanismos inerentes à ativação por LPS, reduzindo a eficácia de ST6Gal-1 extracelular. Por outro lado, a modificação no perfil de CDs de murganhos deficientes em ST6Gal-1 poderá relacionar-se com uma predisposição para um estado inflamatório severo. Com isto, o trabalho desenvolvido abriu futuras linhas de investigação, nomeadamente explorar outros fatores envolvidos na (de)sialilação α2,6 de CDs, podendo ter impacto em imunoterapia com uso de CDs.--------------------------ABSTRACT: Dendritic cells (DCs) are vital for immunomodulation and the initiation of adaptive immune responses, whereas sialic acids (Sias) are potential immunomodulators. These cells express high levels of sialyltransferase ST6Gal-1, responsible for transferring Sias to the terminal position of oligosaccharide chains. Indeed, DCs’ maturation is associated with decreased cell surface sialylation. Although its biological significance is unknown, the soluble, extracellular form of ST6Gal-1 increases in cancers and inflammation. However, extracellular ST6Gal-1 was recently identified as modulator of hematopoiesis. Considering that DCs play a crucial role in the initiation of a productive anti-cancer immune response, a link between extrinsic sialylation by the extracellular ST6Gal-1 on DC function needs to be investigated. We hypothesize that extrinsic α2,6 sialylation of DCs diminishes their maturation features upon lipopolysaccharide (LPS) stimulation. The main goal was to extrinsically α2,6 sialylate mice bone marrow derived DCs (BMDCs) and to evaluate their maturation and cytokine profiles upon LPS stimulation (by Flow Cytometry and ELISA, respectively). Unlike the hypothesis, we observed that BMDCs’ profile is not modulated, even using several approaches. In contrast, the consequence of lacking cell surface α2,6 Sias in DC maturation was assessed by analysing: 1) sialidase treated BMDCs, 2) BMDCs from mice lacking ST6Gal-1 and 3) DCs from mice airways, comparing wild type with ST6Gal-1 knockout mice. These results suggest that overall lack in α2,6 Sias is related with increased expression of major histocompatibility class II (MHC-II). Although appearing to be controversial findings, other intracellular mechanisms might be occurring upon LPS-induced BMDC activation, probably reducing extracellular ST6Gal-1 effect. In opposite, the modification observed in DC profile of ST6Gal-1 knockout mice might be related to its predisposition to a more severe inflammatory status. With this, the developed work opened future lines of investigation, namely exploring other factors involved in α2,6 (de)sialylation of DC, which might have influence in immunotherapy using DCs.