Structural features of the intracellular domains of the cystic fibrosis transmembrane conductance regulator

Cystic fibrosis (CF) is the most common human genetic disease, occurring prevalently in the Caucasian population at a rate of 1 to 2500 newborns. It is an autosomal recessive disease caused by mutations in the cystic fibrosis trans-membrane conductance regulator (CFTR) gene, which encodes a chloride channel expressed mainly in epithelial cells, but which is also involved in the bicarbonate–chloride exchange. The most common CF symptoms include progressive lung disease and chronic problems of the digestive apparatus (Riordan et al., 1989), whose degree of severity depends on other genetic and/or environmental factors. CF pathogenesis is characterised by the build-up of thick, sticky mucus in multiple mucin-producing organs, such as lungs, sinuses, intestine, pancreas and reproductive organs. For this reason, CF is also denominated mucoviscidosis, implying that mucins - polymeric, gel-forming O-linked glycoproteins responsible for the viscoelastic properties of the mucus - play a critical role in the disease (Kreda et al., 2012). The aim of the present Ph. D. work was to investigate the structural features of two CFTR domains: the nucleotide binding domains (NBDs) - responsible for the gating mechanisms of the channel, and which have been proposed to serve as drug targets - and the regulatory domain (RD), directly involved in the activation of the channel. Knowledge of these aspects could likely improve understanding of the aberrant functionality of defective CFTR, and also help designing therapeutic strategies to either correct the defective protein in situ, and/or to potentiate its physiologic channel activity. The present thesis refers essentially to the four published papers containing most of the results obtained during the 3 year-doctorate course. The first one reports on some biochemical and structural features of NBDs, which were investigated using biochemical assays and measures of small angle x ray scattering (SAXS), while the second paper dealt with the interaction of NBDs with a potentiator (2-pyrimidin-7,8-benzoflavone, PBF) of CFTR activity. Instead, the third and the fourth papers considered RD under non-phosphorylated and phosphorylated conditions, and the influence of phosphorylation on the conformation of the domain as followed by circular dichroism (CD) and SAXS experiments. Briefly, the obtained results allowed us to draw the following principal conclusions. NBDs When in an equimolar mixture and in the presence of ATP, NBDs form a dimer, whose conformation can be significantly changed by PBF. In addition, data could be exploited to reconstruct the ab-initio model of NBDs both as dimer (with or without PBF) and as isolated monomers. RD In this case, obtained results on biochemical, structural and thermodynamic RD aspects allowed us to reconstructing a low-resolution, 3-D model of the native and phosphorylated protein, and to underline how phosphorylation induces the conformational change of the domain and the decreasing of RD stability

The "Hotelera Nacional de Chile" (HONSA): modern tourism in the desert territory in northern Chile

The modern leisure habits result of the right to spare time, increased mobility due to improved transport, education through travel, and enhancement of healthy environments, consolidated in the Chilean desert, a series of modern architectures linked to its context. In November 1933 the Ferrocarriles del Estado began publishing the magazine En Viaje (On Tour), which was the means of disseminating the values and tourism ventures in the country. The magazine precedes the enactment of the law of the annual holiday in January 1934. Since then, the State implemented a territorial politics implementation of tourist services, but takes on greater emphasis from the foundation of the Consorcio Hotelero in 1944, which declares its desire to build hotels in Northern Chile. That entity then joins with the Organización Nacional Hotelera, and together they are called Hotelera Nacional S.A. (HONSA).Peer Reviewe

A Portfolio Model for Teaching Writing and Thinking

The college composition course is increasingly viewed as a pivotal course in fostering in students the skills they will need for meaningful participation in the discourse of the academy. This course is often the students\u27 initiation into an academic environment that emphasizes the significance of the written word. Because of the nature of teaching the abstract and elusive subject of writing, the course presents significant challenges for many composition instructors. This thesis focuses on the development of a student writing portfolio that provides a powerful means of addressing these issues. The work required to complete the portfolio fosters the students\u27 transition from their original diction to the discourse that meets the standards of their academic community. The portfolio process does so by developing the critical thinking dispositions and abilities needed to succeed in the academic environment. Through the work required to complete the portfolio, students develop the dispositions of self-awareness, intrinsic motivation, and the openness to reflect on their writing process and product. The portfolio process shifts the locus of instruction from the teacher to the students and is a concrete means for students to understand the evolution of their thoughts as they make the rhetorical choices that shape their written discourse. The first chapter of this thesis establishes the general context within which this portfolio model was implemented. This is followed by an analysis of recent cognitive theories of writing as related to writing. Through a discussion of the works of Richard Paul and Robert Ennis, the third chapter of this thesis presents the critical thinking framework that informs the curriculum. The fourth chapter describes the portfolio model and discusses the type of in-class instruction required to prepare students to complete the portfolio. The final chapter discusses the impact of the portfolio on students, faculty, and the institution. The portfolio proved to be a powerful tool in creating many benefits to students, faculty, and the institution. Most significantly, the portfolio was important in bringing about a cultural change, one that recognizes the importance of developing student writing through an interdisciplinary approach to establish writing across the curriculum

Social Sciences, Complexity and Sociology of the Present in Edgar Morin

The article intends to revisit the contribution of the french thinker Edgar Morin 1921- to the construction of a plural and open method of research in Social Sciences We will have as theoretical-epistemological basis the sociology of the present an approach of social phenomena developed by the author during three decades from the 1940s to the 1970s constituting the matrix of complex thinking The present work defends the idea that the central categories of the present sociology such as phenomenon crisis and event as well as the so-called living method of empirical research are still fundamental today in the sense of proposing an opening of the social sciences to phenomena increasingly more complex and multidimensional This presupposes the researcher s subjective and objective engagement narrative ability and sensitivity to grasp revealing detai

Geodiversity and the interactions of socio-natural systems in an Anthropocene perspective

Earth Sciences' investigations allow us to know that the planet Earth has an age of 4, 6 billion years. During this elapsed time many processes changed radically some aspects of the planet. In the first four billions of Earth's history, life was in its initial stages and was restricted to the ocean bodies. In the other remaining 500 millions of years, living organisms became more diversified, occupied the continental lands and the human society started to participate in the Earth System at about 12.000 years ago, although our species were already present at the planet for at about 200 million years. This means that human's presence in the planet is just a small fraction of the Earth's history. But, on the other hand, human's modern lifestyle caused critical changes in this system, what led some scientific currents to say that we are responsible for the global warming. Beside this, the International Commission on Stratigraphy - ICS, which is the scientific body that sets the global standard for the time scale that expresses the history of the Earth, has a working group that is nowadays discussing the establishment of a new geological epoch known as Anthropocene. This new geological epoch is marked by substantial changes, in part irreversible, to the Earth System that are comparable to or greater in magnitude to other natural phenomena or processes that occurred previously in the planet, such as glaciers and volcanic activity. Will be discussed here the interactions between human societies and the geodiversity elements, which includes minerals, rocks, soils and reliefs, throughout the human history, focusing on the needs of resources to sustain the modern urban life and the myriad of limits, values and services of natural systems and their abiotic elements. Some examples will be presented, including the reality and conflicts of the geodiversity use in Chapada Diamantina, an ancient diamond mining region in the Northeast of Brazil

GEODIVERSITY AND THE INTERACTIONS OF SOCIO-NATURAL SYSTEMS IN AN ANTHROPOCENE PERSPECTIVE

Earth sciences investigations allow us to know that the planet Earth is 4,6 billion years old. During that time a great number of processes have radically changed some aspects of the planet. In the first four billion years of Earth´s history life was in its initial stages and restricted to the ocean bodies. For the other five hundred million years remaining the living organisms have  become more diverse, they occupied the continental lands and the human society became a part of the Earth System  some  12 thousand years ago, even though our species had already been present on the planet for about 200 million years. That means that human presence on the planet is only a tiny fraction of the Earth´s history. Yet, on the other hand, the modern lifestyle of human beings has caused dramatic changes in this system, which has led some scientific movements to say that we are responsible for global warming. Besides, the International Commission on Stratigraphy - ICS, a scientific body which sets the global standard for time scale that tells the history of the Earth has a working group today that discusses  the advent of a new geological epoch known as the Anthropocene. This new geological epoch is marked by significant, partially irreversible changes in the Earth System comparable or even far greater in magnitude to other phenomena or natural processes that have previously occurred on the planet as glaciers and volcanic activity. It will  discuss the interactions between human societies and the elements of geodiversityincluding minerals, rocks, soils and reliefs, throughout human history, focusing on the resources needs to support modern urban living and the myriad boundaries, values and services of natural systems and their abiotic elements. There are some cases, including the reality and conflicts in the use of geodiversity in Chapada Diamantina,  a former diamond mining region in the Northeast of Brazil. Key-words: Socio-natural Systems. Anthropocene. Geodiversity. Chapada Diamantina.As investigações das Ciências da Terra permitem-nos saber que o planeta Terra tem 4,6 bilhões de anos. Durante esse tempo, muitos processos mudaram radicalmente alguns aspectos do planeta. Nos primeiros quatro bilhões de anos da história da Terra, a vida estava em seus estágios iniciais e se restringia aos corpos oceânicos. Nos outros 500 milhões de anos restantse, os organismos vivos se diversificaram, ocuparam as terras continentais e a sociedade humana passou a partiripar do Sistema Terrestre há cerca de 12 mil anos, embora nossas espécies já estivessem presentes no planeta por cerca de 200 milhões de anos. Isso significa que a presença humana no planeta é apenas uma pequena fração da história da Terra. Mas, por outro lado, o estilo de vida modern do ser humano causou mudanças críticas nesse Sistema, o que levou algumas correntes científicas a dizer que somos os responsáveis pelo aquecimento global. Ao lado disso, a Comissão Internacional de Estratigrafia – ICS, órgão científico que estabelece o padrão global para a escala de tempo que expressa a história da Terra, possui um grupo de traalho que discute hoje o estabelecimento de uma nova época geológica conhecida como Antropoceno. Esta nova época geológica é marcada por mudanças substanciais, em parte irreversíveis, no Sistema Terrestre que são comparáveis ou maiores em magnitude a outros fenômenos ou processos naturais que ocorreram anteriormente no planeta, como geleiras e atividade vulcânica. Serão discutidas as interações entre as sociedades humanas e os elementos da geodiversidade, que inclui minerais, rochas, solos e relevos, ao longo da história da humanidade, enfocando as necessidades de recursos para sustentar a vida urbana moderna e a miríade de limites, valores e serviços de sistemas naturais e seus elementos abióticos. Alguns exemplos são apresentados, incluindo a realidade e os conflitos do uso da geodiversidade na Chapada Diamantina, uma antiga região de mineração de diamantes no Nordeste do Brasil.   Palavras-chave: Sistemas sócio-naturais. Antropoceno. Geodiversidade. Chapada Diamantina

Natural and Cultural Landscapes in Atacama Desert: Between Tradition and Innovation

Climatic conditions modeling the landscape of the Chilean northern region are examined, along with how they could model different strategies to be inhabited by various demographic contingents in time. These experiences have persisted in the different geographic spaces of Atacama Desert, from the Andes at an elevation higher than 2000 m.a.s.l., going through the intermediate depression between 2000 and 500 m.a.s.l., to the coastline panorama. In the various shades of the desert climate and the experiences of several populations, life styles and spatial conceptions were posed in terms of their cosmic dimension from a deterministic view and pragmatic apprehension to a contemplation-like view. These conceptions between man and the landscape have assumed different relations of technology use, natural and energy resources, and a constructive-architectonic design in Atacama Desert, which have remained as monuments in the Chilean southern space

From Ontology to Anthropotechnics: Humanism, Media and Domestication of Being

In this essay we intend to approach how Peter Sloterdijk relates to the thinking of Martin Heidegger when questioning the humanist definition of man and proposing the notion of Anthropotechnics To this end the article begins by exposing Heidegger s conception of Technique and Humanism and Ernst J nger s influence on this issue Then when dealing with the question of being and ontological difference the peculiar treatment that Sloterdijk offers to the ontological question is presented by articulating the history of being with a kind of genealogy of the clearing bringing to the foreground certain intuitions of Friedrich Nietzsche about the beginnings of the human species To conclude Sloterdijk s thinking is developed culminating in what he calls ontoanthropology a notion presented in the work La Domestication de l tre and possible applications to issues related to biotechnology and contemporary media - which allows us to think a machinic history of being under the doubly complex bias of anthropology and ontolog