RCAAP Repository

Background and Aims It is accepted that contemporary allopolyploid species have originated recurrently, but very few cases have been documented using multiple natural formations of the same species. To extend our knowledge, we have investigated the multiple origins, genetic variation and structure of the allotetraploid grass Brachypodium hybridum with respect to its progenitor diploid species B. distachyon (D genome) and B. stacei (S genome). For this, our primary focus is the Iberian Peninsula, an evolutionary hotspot for the genus Brachypodium. Methods We analysed 342 B. hybridum individuals from 36 populations using ten nuclear SSR loci and two plastid loci. The B. hybridum genetic profiles were compared with those previously reported for B. stacei and B. distachyon. In addition, phylogenetic analysis of the plastid data was performed for a reduced subset of individuals. Key Results The nuclear simple sequence repeat (SSR) genetic analysis detected medium to high genetic diversity, with a strong south-to-north genetic structure cline, and a high selfing rate in B. hybridum. Comparative genetic analysis showed a close relatedness of current B. hybridum D allelic profiles with those of B. distachyon, but a lack of similarity with those of B. stacei, suggesting another B. stacei source for the B. hybridum S alleles. Plastid analysis detected three different bidirectional allopolyploidization events: two involved distinct B. distachyon-like ancestors and one involved a B. stacei-like ancestor. The south-eastern Iberian Peninsula B. hybridum populations were more genetically diverse and could have originated from at least two hybridization events whereas north-eastern/north-western Iberian Peninsula B. hybridum populations were less diverse and may have derived from at least one hybridization event. Conclusions The genetic and evolutionary evidence supports the plausible in situ origin of the south-eastern and northern Iberian Peninsula B. hybridum allopolyploids from their respective local B. distachyon and unknown B. stacei ancestors. The untapped multiple origins and genetic variation detected in these B. hybridum populations opens the way to future evolutionary analysis of allopolyploid formation and genomic dominance and expression in the B. hybridum–B. distachyon–B. stacei grass model complex.

Identity and discrepancies between the teachings of the University of Coimbra and those of the University of Évora, and their integration in the Commentary to Aristotle produced by Portuguese Jesuits known as Cursus Aristotelicus Conimbricensis.

Next-generation sequencing has revolutionized clinical diagnostic testing. Yet, for a substantial proportion of patients, sequence information restricted to exons and exon-intron boundaries fails to identify the genetic cause of the disease. Here we review evidence from mRNA analysis and entire genomic sequencing indicating that pathogenic mutations can occur deep within the introns of over 75 disease-associated genes. Deleterious DNA variants located more than 100 base pairs away from exon-intron junctions most commonly lead to pseudo-exon inclusion due to activation of non-canonical splice sites or changes in splicing regulatory elements. Additionally, deep intronic mutations can disrupt transcription regulatory motifs and non-coding RNA genes. This review aims to highlight the importance of studying variation in deep intronic sequence as a cause of monogenic disorders as well as hereditary cancer syndromes.

Vitiligo is a dermatological disease characterized by the presence of hypopigmented macules on the skin. Considering that its effects are not limited to the biological dimension of the subject, it is assumed negative impacts on the quality of life of their bearers. Yet, little attention has been giving to this phenomenon in Brazilian studies. This research sought to overcome this gap by verifying the relationship between sociodemographic variables of people with Vitiligo, as well as their perceptions of discrimination and severity of the disease in their qualities of life. It is a quantitative study with a descriptive and exploratory nature, in which 200 Brazilians with Vitiligo participated, most of them female (73%), with white skin colour (50.5%) and predominantly residents of Southeast Brazil (31.02%). For data collection, a sociodemographic questionnaire and the Vitiligo-specific health-related quality of life instrument (VitiQoL) scale were used. Results revealed that female participants, with black skin colour, low income and white patches in areas of easy social perception showed worse rates of quality of life. The findings are discussed with pertinent literature, and it is expected that they contribute to the development of public policies aiming to improve the quality of life of Brazilians with Vitiligo.

The process of spontaneous subduction initiation at passive margins plays a central role in the plate tectonics theory, in particular in the Wilson Cycle paradigmatic concept, which states that oceans form, evolve and finally close. The Wilson Cycle requires that after a certain time of oceanic drifting passive margins are reactivated and subduction initiates. However, the process of transformation of passive continental margins into active continental margins with subduction zones is still far from understood, and spontaneous transition examples between these two types of margins are not known. In addition, recent works based on theoretical calculations and physical modeling showed that it is mechanically unfeasible to form a new subduction system in isolation from an already existing one, i.e. spontaneous subduction initiation. One way to solve this problem is to consider that subduction initiation may generally be induced by the proximity of another subduction zone or by stress transference from a nearby collision belt, i.e. induced subduction initiation. Therefore, passive margins in the proximity of pre-existing subduction zones would represent preferential sites for the formation of new subduction zones. In this work, the Gibraltar Arc and the Southwest Iberia Margin are used as case studies to investigate the role that the orogenic arcs may have in the formation of new subduction systems at passive margins. The Atlantic margins are generally described as the typical case of passive margins, often termed Atlantic type margins. However, there are at least two regions where the Atlantic oceanic lithosphere is being consumed in subduction zones: in the Scotia and in the Lesser Antilles arcs (in the Southwestern and central West Atlantic, respectively). These subduction zones seem to have been transferred from the Eastern Pacific ocean to the Atlantic domain and potentially represent precursors to a system of convergent zones that might ultimately result in the closure of the Atlantic Ocean. However, in these two systems the oceanic lithosphere has been subducted since at least the Early Cenozoic, without lateral propagation of the subduction zones along the adjacent Atlantic passive margins. The Gulf of Cadiz, i.e. the foreland of the Gibraltar orogenic arc, has been proposed as a potential locus for a subduction zone to propagate into the open Atlantic. On the other hand, the proximity of the Gibraltar collision belt to the Southwest Iberia Margin, together with the existing overall convergence between II Africa and Iberia, induces compressive stresses that, in association with the existence of more than 100 km long active thrusts (e.g. Horseshoe Fault and Gorringe Bank), make this margin a strong candidate for the nucleation of a new subduction zone. In order to better evaluate the post-Miocene tectonics and the main tectonic driving mechanism operating in the Gulf of Cadiz an up-to-date tectonic map of this area was produced. This map was based on the coupled analysis of a multi-survey MCS dataset and the recently compiled high resolution bathymetry dataset (the SWIM bathymetry). The mapping revealed the existence of three main systems of tectonic structures: i) the subduction-related Gulf of Cadiz Accretionary Wedge (CGAW); ii) a set of WNW-ESE striking dextral strike-slip faults (the SWIM fault system); and iii) a group of NE-SW striking northwest-directed thrusts located in the Southwest Iberia Margin (the NE-SW thrust system). The subduction-related accretionary wedge (GCAW) is materialized on the seafloor by a west dipping U-shaped surface and consists in an eastward thickening pile of westwards thrusted sediments. There are evidences that this thrust wedge is active and propagating westward. The SWIM fault system is a group of WNW-ESE striking subvertical strike-slip faults extending from the eastern part of the Gulf of Cadiz, i.e. the northwest Moroccan shelf, to the Horseshoe Abyssal Plain. These faults were interpreted in this work as the Present day dextral reactivation of the old Mesozoic Tethyan plate boundary. The NE-SW striking thrust system is a group northwest directed thrusts located along the Southwest Iberia Margin, comprising the Horseshoe fault, the Marquês de Pombal fault, the Tagus Abyssal Plain fault and the Gorringe northern thrust. This NESW thrust system seems to be the result of the migration of the deformation, in the Pliocene-Quaternary, from the realm of the Gibraltar wedge to the west (onto the Horseshoe fault region) and to the north along the West Portuguese Margin. These structures may be the expression of a new compressive deformation front. Besides these three tectonic systems, other important structures were also promptly recognized such as the ENE-WSW to E-W striking system of thrusts (e.g. the Portimão pop-up and the Coral Patch Ridge), related with the overall Cenozoic NubiaIII Iberia N-S convergence, and NE-SW striking Cadiz fault, a dextral strike-slip fault that probably accommodates part the westward movement of the Gibraltar Arc. The analysis of the multibeam bathymetry data from the northwestern part of the Gulf of Cadiz also revealed the existence of several intriguing kilometric crescentic depressions lying at depths between -4300 m and -4700 m, never before reported to occur at such great depths in the scientific literature. These features are located in the Horseshoe Valley between two major tectonic structures: the GCAW and the Horseshoe fault. Morphological parameterization of these features, coupled with detailed analysis of multi-channel and middle resolution seismic profiles, showed that these crescentshaped features were formed due to the existence of specific interaction between: a) regional active thrusts on top of which most crescentic depressions are carved; and b) tectonically induced scouring comprising localized erosion and simultaneous progradational sedimentation, produced by downslope turbiditic currents. The obtained results also suggest a possible contribution of fluid migration and extrusion processes, such as mud volcanism and associated pockmark formation, besides gravity driven landslides and slumping, in the development of the studied crescentic depressions. The active (mainly blind) thrusts in which the crescentic depressions are carved root in the GCAW décollement layer, to the west of the GCAW deformation front. Therefore, the crescentic depressions are interpreted as the morphological expression of the westward propagation of the deformation related with the GCAW, into the Horseshoe Valley domain. Besides the new produced cartography of the Gulf of Cadiz, the present work also benefited from the instrumental use of analog modeling experiments. Three main different modes of tectonic interference between the SWIM strike-slip fault system (related with the overall Nubia-Iberia convergence) and the GCAW (related with the Gibraltar subduction) were tested through analog sand-box modeling, namely: a) An active accretionary wedge on top of a pre-existent inactive basement fault; b) An active strike-slip fault cutting a previously formed, inactive, accretionary wedge; and c) Simultaneous activity of both the accretionary wedge and the strike-slip fault. The results obtained and the comparison with the natural deformation pattern favor a tectonic evolution comprising two main steps: i) the development of the Gulf of Cadiz Accretionary Wedge on top of inactive, Tethyan-related, basement faults (Middle Miocene to ~1.8 Ma); ii) subsequent reactivation of these basement faults with dextral IV strike-slip motion (~1.8 Ma to Present) simultaneously with continued tectonic accretion in the GCAW. These results exclude the possibility of ongoing active SWIM wrench system cross-cutting an inactive GCAW structure. The results also support a new interpretation of the SWIM wrench system as fundamentally resulting from strikeslip reactivation of an old (Tethyan-related) plate boundary. Detail mapping in the Horseshoe Abyssal Plain also revealed the existence of a new morphotectonic pattern near the intersection (corner zone) of the SWIM 1 fault and the Horseshoe fault. Based on combined analog and numerical experiments this pattern was interpreted as resulting from the (wrench-thrust) tectonic interference between two of the main tectonic systems recognized in the Gulf of Cadiz area: the SWIM faults and the NE-SW thrusts. Finally, the results presented in this work favor a hypothetic scenario in which the Gibraltar subduction is active, but decreasing in activity since the Miocene, at the same time that an incipient subduction zone may be nucleating in the Southwest Iberia Margin. The Gulf of Cadiz may be thus seen as a place where the proximity of a preexistent subduction system could be inducing the formation of a new subduction zone in the Atlantic.

The alternative splicing code that controls and coordinates the transcriptome in complex multicellular organisms remains poorly understood. It has long been argued that regulation of alternative splicing relies on combinatorial interactions between multiple proteins, and that tissue-specific splicing decisions most likely result from differences in the concentration and/or activity of these proteins. However, large-scale data to systematically address this issue have just recently started to become available. Here we show that splicing factor gene expression signatures can be identified that reflect cell type and tissue-specific patterns of alternative splicing. We used a computational approach to analyze microarray-based gene expression profiles of splicing factors from mouse, chimpanzee and human tissues. Our results show that brain and testis, the two tissues with highest levels of alternative splicing events, have the largest number of splicing factor genes that are most highly differentially expressed. We further identified SR protein kinases and small nuclear ribonucleoprotein particle (snRNP) proteins among the splicing factor genes that are most highly differentially expressed in a particular tissue. These results indicate the power of generating signature-based predictions as an initial computational approach into a global view of tissue-specific alternative splicing regulation.

T cell activation requires the integration of signals that arise from various types of receptors. Although TCR triggering is a necessary condition, it is often not sufficient to induce full T-cell activation, as reflected in cell proliferation and cytokine secretion. This has been firmly demonstrated for conventional αβ T cells, for which a large panel of costimulatory receptors has been identified. By contrast, the area remains more obscure for unconventional, innate-like γδ T cells, as the literature has been scarce and at times contradictory. Here we review the current state of the art on the costimulatory requirements of γδ T cell activation. We highlight the roles of members of the immunoglobulin (like CD28 or JAML) or tumour necrosis factor receptor (like CD27) superfamilies of coreceptors, but also of more atypical costimulatory molecules, such as NKG2D or CD46. Finally, we identify various areas where our knowledge is still markedly insufficient, hoping to provoke future research on γδ T cell costimulation.

Vasoactive intestinal peptide (VIP), an important modulator of hippocampal synaptic transmission, influences exploration and hippocampal-dependent learning in rodents. Homosynaptic long-term depression (LTD) and depotentiation are two plasticity phenomena implicated in learning of behavior flexibility and spatial novelty detection. In this study, we investigated the influence of endogenous VIP on LTD and depotentiation induced by low-frequency stimulation (1 Hz, 900 pulses) of the hippocampal CA1 area in vitro in juvenile and young adult rats, respectively. LTD and depotentiation were enhanced by the VIP receptor antagonist Ac-Tyr(1) , D-Phe(2) GRF (1-29), and the selective VPAC1 receptor antagonist, PG 97-269, but not the selective VPAC2 receptor antagonist, PG 99-465. This action was mimicked by an anti-VIP antibody, suggesting that VIP, and not pituitary adenylate cyclase-activating polypeptide (PACAP), is the endogenous mediator of these effects. Selective inhibition of PAC1 receptors with PACAP (6-38) enhanced depotentiation, but not LTD. VPAC1 receptor blockade also revealed LTD in young adult rats, an effect abolished by the GABAA antagonist bicuculline, evidencing an involvement of GABAergic transmission. We conclude that inhibition of LTD and depotentiation by endogenous VIP occurs through VPAC1 receptor-mediated mechanisms and suggest that disinhibition of pyramidal cell dendrites is the most likely physiological mechanism underlying this effect. As such, VPAC1 receptor ligands may be considered promising pharmacological targets for treatment of cognitive dysfunction in diseases involving altered GABAergic circuits and pathological saturation of LTP/LTD like Down's syndrome and temporal lobe epilepsy.

Axonal and dendritic outgrowth are fundamental processes in the development of the nervous system. During this period, neurons change their morphology from a simple bipolar shape into a mature complex shape. Neurons develop dendrites and extend long or short axons that travel through a complex path until reaching target cells and form functional and accurate neuronal circuits.

This work intends to develop an investigation within the jazz studies, with particular emphasis on the contribution of five Portuguese guitarists to the dissemination, growth, transformation and popularization of jazz in Portugal. Making use of bibliographical research and fieldwork, this thesis will analyze the work and contribution of Carlos Menezes, José Luís Simões, João Maló, Armindo Neves and Luís Stoffel to the musical community and to the Portuguese jazz scene. A conceptual discussion of Diaspora, Globalization and Scene will foster an analysis of the collected data on these five jazz guitar pioneers and create a reflection on the emergence of new terms and their interrelation. These three concepts will also work as head topics which will allow to analyze, among others, the meanings of syncretism, transnationalism, transculturality, transmigration, translocality, community, glocalization and their impact on the professional path and work of the five featured musicians. These concepts are also related to homogenous or heterogeneous and hybrid musical elements. These elements are sometimes responsible for the emergence of new practices and discourses that culminate in the creation of a new transidiomatic musical language. The practical and artistical component of this work includes Cenas de Uma Vida no Bosque, an original composition written within the scope of this investigation, and the arrangements of “Flor Sem Tempo”, “Portugal, Portugal” and “Lisboa à Noite”, three songs associated with the Portuguese popular music and related to the careers of the five featured musicians throughout this thesis. Both the original composition and the arrangements were performed by a septet led by me and recorded in audio and video. Cenas de Uma Vida no Bosque will be released as an album after the presentation of this PhD thesis.

Migration infrastructures have usually been identified with stable sociomaterial arrangements controlling migration (e.g. airports and detention camps), stressing highly stratified power geometries and hierarchies. Recent debates about arrival infrastructures, however, have highlighted the informal, ephemeral and improvisational character of ‘bottom-up’ infrastructures. Departing from a widened understanding of infrastructure, this paper looks at migrants’ businesses as urban infrastructures assembling various kinds of mobilities. In particular, we address small businesses established by Senegalese migrants in Brazil, and Brazilianowned cafés in Portugal. We approach these businesses as urban infrastructures where different forms of mobilities overlap and interact, exposing various trajectories and scales of circulation. While the businesses in Brazil cater mainly for Senegalese and other migrants’ needs (money transfer, ICTs, and job offers), the Brazilian-owned coffee shops in Portugal function as sites of co-working and sociality of tourists, digital nomads, and other urban creatives. Building on ethnographic fieldwork in the cities of São Paulo and Caxias do Sul (Brazil) and in Lisbon (Portugal), this paper makes innovative connections between migration research, mobility studies and urban theory. We discuss the infrastructural production of transnational and local mobilities and how these businesses both result from and facilitate the existence of mobile lifestyles.

This project results from the process of carrying out the inventory of the epigraphic heritage existing in the former Convento de S. Francisco de Lisboa and which today houses the a Faculdade de Belas Artes da Universidade de Lisboa (FBAUL), Faculty of Fine Arts of Lisbon. If we consider that the convent originated in the thirteenth century, it implies an interval of almost eight centuries of history. In these 800 years of history the building has, of course, gone through many situations that changed its structure, from fires to earthquakes. However, there are inscriptions that go from the Medieval Era to our Contemporary Era. In fact we studied and invented a total of 47 inscriptions. The focus of this investigation is on the inventory process, in other words, the main interest lies in the application of a working methodology that can achieve this goal effectively. To establish the field of work with some rigor we put, on the one hand, the historical information and, on the other, our own search and identification of the inscriptions. One can say objective and subjective aspects respectively. However, both necessary aspects, a moment devoted to searching, identifying, reading and their proper photographic record are then confronted with historical documents to objectively clarify our observation on the ground, thus reducing the possibility of error. Crossing aspects that allowed the completion and completion of inventory sheets. Our big goal. The journey through the building motivated another aspect that was also present in this project, although in a secondary way, perhaps the subject of another investigation. The description of a whole typography that we have been observing, information by text, by letters, by numbers that did not fit directly with our research, but which we also considered necessary to expose. We conclude with proposals for the exposure of this existing heritage in the building of FBAUL, since we verify in situ their complete ignorance on the part of the people who usually walk through the building. We believe that inventory can be a factor that changes this situation and allows its valuation and consequent preservation.

Currently a paradigm change is happening in the collaboration between design and social sciences, it’s a change from a user centered design process to participative experiences. This recent approach requires new ways of thinking, feeling and developing the process. The participative experience isn’t simply a method or a set of methodologies but a new attitude towards people. The inclusion of people, from different backgrounds, is changing the landscape around the design practice, creating new collective creativity domains towards more sustainable ways of living in the future. This dissertation explores some meanings and practices associated with participative experience, clarifying the importance of the organization and prioritization of data during the process, having the assertive choice of the methods and activities as the final objective. From this point of view, the present investigation lead to the creation of a Toolkit. In this Toolkit are shown some of the key factors to consider when planning and evaluating a process that involves different people and experiences. More than translating the process through stages, this toolkit leads designers and design teams to take more conscious decisions when comes to developing a project.

Effective CD8(+) T-cell responses against tumor or microbial antigens that are not directly expressed in antigen-presenting cells (APCs) depend on the cross-presentation of these antigens on MHC class I in APCs. To identify signaling molecules that regulate cross-presentation, we used lentiviral-based RNA interference to test the roles of hundreds of kinases and phosphatases in this process. Our study uncovered eight previously unknown genes, consisting of one positive and seven negative regulators of antigen cross-presentation. Depletion of Acvr1c, a type I receptor for TGF-β family of signaling molecules, led to an increase in CD80 and CD86 co-stimulator surface expression and secreted IL-12 in mouse bone marrow-derived DCs, as well as antigen-specific T-cell proliferation.

A common consequence of sticking to a research topic for a fair amount of time is that it starts colonising your everyday life to a point where you may find yourself asking questions to every new acquaintance as if they were participants in your project. Your friends may become tired of your constant interrogations, but unknown people might simply take you as someone with a peculiar sense of curiosity. I believe this is what recently happened to me when coming back from a conference and decided to call an Uber driver at Lisbon airport. This chapter explores some of the functionalities mental maps offer to migration research. Mental maps (or cognitive maps) have long helped understanding how individuals use and perceive local space. Yet, as a visual method, mental maps may be produced and analysed in distinct ways. This chapter navigates through existing research employing mental maps and argues for an interactive approach to mental map analysis, in which the researcher-participant engagement becomes as fundamental as the actual visualisation produced. Based on fieldwork with migrants in Lisbon, Portugal, the chapter illustrates the methodological potential of mental maps for yielding information about the ways migrants actively mobilise urban resources.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation that is not fully reversible even under bronchodilators effect, caused by a mixture of small airway disease – obstructive bronchiolitis – and parenchymal destruction – emphysema. At the present time, COPD is the fourth leading cause of death and its prevalence and mortality are expected to continue increasing in next decade. Spirometry is the most reproducible way to measure lung function and is nowadays the best tool to diagnose airflow limitation and, consequently, diagnose COPD itself. Biomarkers for diagnosis and/or prognosis as well as novel targets for the development of more effective therapies for COPD are still needed. Proteomics has the capacity to provide large-scale information and consequently it has the potential to expand previous knowledge on COPD. Surprisingly, given the need for new biomarkers in COPD and the power of proteomics, proteomics have been quite neglected so far. Up to date only 50 reports (14 are reviews) match the search at Pubmed (http://www.ncbi.nlm.nih.gov/pubmed, accessed June 23, 2011) for COPD proteomics. Hence, there is a clear need to engage clinically valuable proteomics studies in order to match the need for new biomarkers in COPD. In last decade, the shotgun proteomics approach has become the method of choice for identifying and quantifying proteins in most large-scale studies. Compared with 2DE, shotgun proteomics allows higher data throughput and better protein detection sensitivity. This strategy is based on trypsin digestion of proteins into peptides. This produces a complex peptide mixture that is then separated by one- or multiple dimensional liquid chromatography (LC) and subjected to peptide sequencing using tandem mass spectrometry (MS/MS) before automated database searching. In the present work we have employed different methodologies within shotgun proteomics to generate solid and comprehensive data in COPD. There are quite a lot biological materials that can be used to investigate biomarkers for this disease. Although COPD is now known to possess a systemic inflammation xii component which is responsible for affecting other organs, it is in the lung that the events that lead to breathless take place. Investigating to the lung directly is therefore an optimal strategy to be able to identify proteins that may not be detectable elsewhere either because they are not present or diluted into undetectable concentrations. But this means that lung tissue has to be collected by biopsy which is an extremely invasive technique. But besides tissue biospecimens, other sources of biological materials used to study COPD is biofluids which includes sputum, bronchoalveolar and nasal lavage fluid, exhaled breath condensate, and blood. It had been observed before by means of microscopy that red blood cells (RBCs) from COPD patients showed deformations in their shape. RBCs are crucial to the uptake of oxygen from the lungs to the cells and this transport is dependent on their ability to change shapes rapidly while navigating through blood vessels. In addition, RBCs play a crucial role in antioxidant defense when fighting against oxidative stress, which has long been recognized as feature of COPD. In this work we made use of a RBC membrane fractionation procedure, stable isotope labeling and bidimensional liquid chromatography (strong cation exchange / reverse phase) before sample acquisition using a high-resolution fourier transform - ion cyclotron resonance (FT-ICR) mass spectrometer (Chapter III). A total of 4697 peptides were quantified as present in both COPD and control spectra corresponding to 1083 proteins. Three-hundred and fourteen proteins possessing at least two peptides were identified, 46% of which were annotated as membrane proteins. Golgin-245/p230 (GOLGA4), was identified as overexpressed in COPD, a protein which is reported to be essential for intracellular trafficking and cell surface delivery of tumor necrosis factor-α (TNF), the main proinflammatory cytokine made and secreted by inflammatory macrophages enhancing activation and recruitment of T-cells and ensuring robust innate and acquired immune responses. Chorein or Vacuolar protein sorting-associated protein 13A (VPS13A) is reported to play a role in the cytoskeleton organization has been associated with thorny deformations of circulating erythrocytes, possibly due to red cell membranes deformation. This protein was found to be underexpressed in COPD patients when compared to controls by MS and this underexpression was confirmed by WB. Consequently, underexpression of chorein may play an important role in the deformation of COPD RBCs. Many other interesting proteins were identified in the xiii context of COPD and, additionally, there were a considerable number of proteins described in RBC for the first time (Chapter III). To overcome the difficulty of acquiring fresh biopsies of well characterized patients, we have established in our laboratory a procedure to collect human fresh nasal epithelial cells. We have shown previously that these cells presented similar proteome of epithelial cells presented in the lower airway. Here, two different types of studies were presented using these cells: a study performed on the effects of cigarette smoke, which is the main risk factor for developing COPD (Chapter IV) and a comparative proteomic study between COPD patients and healthy individuals (Chapter V). Both were pioneer studies by investigating the proteome of fresh nasal epithelial cells from cigarette smoker subjects (Chapter IV) or COPD patients (Chapter V). In both studies a high-resolution mass analyzer, the orbitrap, was employed increasing the number of confident peptide/protein identifications. In Chapter IV, ninety-six proteins were found to be differentially expressed between the proteomes of healthy smokers and nonsmokers. These proteins were related to processes of antigen presentation, cell-to-cell signaling and interaction, cell morphology, drug metabolism, DNA repair, energy production or mitochondrial dysfunction. Although requiring further orthogonal validation, our data was consistent with previous evidences showing CD44, MUC5AC or SOD2 differential modulation in smokers due to inflammatory response pathways. In Chapter V, 89968 peptides and 1475 proteins were identified in total, of which 1173 proteins were identified by at least two peptides. We were able to confirm previous evidences that UPR is activated in COPD patients since we were able to observe overexpression in a considerable number of proteins involved in different protein complexes involved in UPR. This includes overexpression of VCP, both components of the Hsp10/Hsp60 chaperone complex (HSPD1 and HSPE1), CALR and two members of a large ER-localized multiprotein complex of at least 11 proteins, PPIB and ERP29. We also observed an increase in expression of proteins related to Nrf2-mediated oxidative stress response such as GSTP1, TXNRD1 and GSR. Additionally, we also report an increase in drug metabolism, as all significantly differentially expressed proteins related to this biofunction were overexpressed in COPD: GSTP1, GSR, AKR1C3 and ANXA2. Further validation by orthogonal methods is needed so that the activation of xiv UPR and Nrf2-mediated oxidative stress response and the increase in drug metabolism on the nasal epithelial cells of COPD patients is fully confirmed. In Chapter VI, serum collected from COPD patients was divided into 4 different groups in all different combinations of presence/absence of the two main features of COPD, chronic bronchitis and emphysema, to study their impact in the serum proteome. Due to its complex protein mixture, serum was first immunodepleted from its most abundant proteins, comprising about 94% of total protein content, before being analyzed by 1D-PAGE – LC-MS/MS (GeLC-MS/MS) in a linear ion trap mass spectrometer. This powerful strategy was able to identify as many as 2856 proteins, of which 929 were identified by two or more peptides. Plasminogen was found to be underexpressed in COPD patients that suffer simultaneously from emphysema and chronic bronchitis, while it maintained about the same expression level over the three other groups of COPD patients and this differential expression was successfully validated by ELISA. It was possible to identify other interesting proteins as TRAF3IP2, which is associated with innate immunity in response to pathogens, inflammatory signals and stress and has also been implicated in airway hyperresponsiveness or Isoform 1 of phosphatidylinositol-glycan-specific phospholipase D (GPLD1), which is GPI degrading enzyme that was described to be responsible for secretion of prostasin, which was the first of several membrane serine peptidases found to activate the epithelium-sodium channel (ENaC). Prostasin was also reported to have a critical role in regulating epithelial sodium transport in normal and pathological conditions in the lung. The work herein presented confirmed a few findings that had already been reported and more important revealed new insights into COPD disease mechanisms as well as provided new candidate biomarkers for these diseases. Further validation and integration of all data obtained into a systems biology approach will certainly contribute to increase knowledge of COPD and ultimately bringing the well being of patients.

In this chapter, I present the making of an ethnographic film, which I filmed during a research project in geography carried out from 2013 to 2017 and entitled Victory Day. The chapter provides a reflection on the use of film to capture political actions, specifically the ones targeting immigrant groups. It also shows the extent to which filmmaking relates to experiences of the participants involved, and to the sensorial experience of a place. With this, it builds on previous works that have highlighted the potential of moving images to represent the sensory, experiences and intersubjectivities. Finally, it tackles the ethics of working in conflict cities, and even more specifically, when participants take a hawkish stand in that conflict.

To effectively plan and manage the use of agricultural land, it is crucial to identify and evaluate the multiple human and environmental factors that influence it. In this study, we propose a model framework to identify the factors potentially explaining the use of agricultural land for wheat, maize, and olive grove plantations at the regional level. By developing a machine-learning model coupled with a model-agnostic approach, we provide global and local interpretations of the most influential factors. We collected nearly 140 variables related to biophysical, bioclimatic, and agricultural socioeconomic conditions. Overall, the results indicated that biophysical and bioclimatic conditions were more influential than socioeconomic conditions. At the global interpretation level, the proposed model identified a strong contribution of conditions related to drainage density, slope, and soil type. In contrast, the local interpretation level indicated that socioeconomic conditions such as the degree of mechanisation could be influential in specific parcels of wheat. As demonstrated, the proposed analytical approach has the potential to serve as a decision-making tool instrument to better plan and control the use of agricultural land.

The connection between tourism and nature justifies the environmental concerns from tourism agents, namely global hotel chains. This paper explores the differences between smaller hotel chains and their larger global counterparts regarding environmentally sustainable practices. The research approach is qualitative, based on the analysis of 40 company websites and in-depth interviews with 18 entrepreneurs and executives. Results suggest that environmental issues are, for most companies, not a response to societal challenges (‘doing the right thing’), but a response to owners’ concerns (‘doing things right’). Hotel chains develop environmental sustainability practices, mainly for cost-reduction purposes, accommodating the owners’ demands for efficiency. Notwithstanding, there are differences according to the chain’s size. Smaller companies are less prone to adopt environmental practices and to invest in communicating them than global chains. Concerning sustainability in the hotel industry, most studies focus on specific topics and discussions. A more holistic approach to sustainability to establish a deeper understanding of sustainable business decisions in the hotel sector is scarce in the literature. This paper addresses this gap by exploring the strategic reasons behind the sustainable practices of hotel companies, namely smaller ones. Managerial implications of the results are also derived in this paper.

Smart specialization strategies are a new EU approach to cohesion policy, meant to deliver growth and development at EU national and regional level. Bearing in mind its focus on place-based development strategies, this paper intends to shed some light on its appropriateness to tackle uneven development and regional growth divergence. The paper showcases Spanish Extremadura growth trajectory. Extremadura is a poor region in the European context that between 2008 and 2014 diverged from the EU average, despite being eligible for EU funding as a convergence region by cohesion policy. In the 2014–2020 programming period, there was a positive dynamic at the beginning, but from 2017 onwards convergence stopped, which indicates that thematic and regional programmes have not delivered results or have not compensated for higher growth level of other Spanish regions. Moreover, research and innovation strategies for smart specialization (RIS3) seem to have limited impacts on place-based economic transformation in less developed regions. From this example, the suitability of the smart specialisation strategy as the core of cohesion policy in the programming period is discussed. It concludes that this strategy is interesting for intermediate development regions with some industrial base but does not seem appropriate as a convergence driver for poorer regions.