Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pretreatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

Abstract Background The thymus is a central lymphoid organ, in which bone marrow-derived T cell precursors undergo a complex process of maturation. Developing thymocytes interact with thymic microenvironment in a defined spatial order. A component of thymic microenvironment, the thymic epithelial cells, is crucial for the maturation of T-lymphocytes through cell-cell contact, cell matrix interactions and secretory of cytokines/chemokines. There is evidence that extracellular matrix molecules play a fundamental role in guiding differentiating thymocytes in both cortical and medullary regions of the thymic lobules. The interaction between the integrin α5β1 (CD49e/CD29; VLA-5) and fibronectin is relevant for thymocyte adhesion and migration within the thymic tissue. Our previous results have shown that adhesion of thymocytes to cultured TEC line is enhanced in the presence of fibronectin, and can be blocked with anti-VLA-5 antibody. Results Herein, we studied the role of CD49e expressed by the human thymic epithelium. For this purpose we knocked down the CD49e by means of RNA interference. This procedure resulted in the modulation of more than 100 genes, some of them coding for other proteins also involved in adhesion of thymocytes; others related to signaling pathways triggered after integrin activation, or even involved in the control of F-actin stress fiber formation. Functionally, we demonstrated that disruption of VLA-5 in human TEC by CD49e-siRNA-induced gene knockdown decreased the ability of TEC to promote thymocyte adhesion. Such a decrease comprised all CD4/CD8-defined thymocyte subsets. Conclusion Conceptually, our findings unravel the complexity of gene regulation, as regards key genes involved in the heterocellular cell adhesion between developing thymocytes and the major component of the thymic microenvironment, an interaction that is a mandatory event for proper intrathymic T cell differentiation.

Sustentabilidade nas organizações: a internalização dos gastos com o descarte do produto e/ou embalagem aos custos de produção

Neste estudo, tem-se como objetivo analisar e discutir crenças, valores e aspectos práticos, considerando que a internalização dos gastos decorrentes do descarte do produto e/ou embalagens deve nortear a gestão de custos de produção de uma empresa. Por tratar-se de área do conhecimento ainda carente de estudos e sem solução consensual por parte de agentes do mercado, realizou-se um ensaio teórico em que são apresentados e discutidos posicionamentos, práticas e ações com potencial para mitigar os efeitos da degradação ambiental decorrentes de descartes inapropriados. Para isso são propostas ações por parte de empresas e de iniciativas voluntárias em negociações de títulos financeiros de compensação das externalidades, os quais foram denominados de créditos de internalização de custos privados (CICPs). Considera-se que o desenvolvimento com sustentabilidade é um processo que envolve negociações entre empresas, governos e sociedade civil, pois as políticas e metas não devem ser apenas economicamente viáveis, mas socialmente justas, ambientalmente corretas e culturalmente compartilhadas.

Scienza, Tecnica, Politica: Il Problema del Metodo nel Pensiero di Jacopo Aconcio

The aim of this PhD thesis is to study accurately and in depth the figure and the literary production of the intellectual Jacopo Aconcio. This minor author of the 16th century has long been considered a sort of “enigmatic character”, a profile which results from the work of those who, for many centuries, have left his writing to its fate: a story of constant re-readings and equally incessant oversights. This is why it is necessary to re-read Aconcio’s production in its entirety and to devote to it a monographic study. Previous scholars’ interpretations will obviously be considered, but at the same time an effort will be made to go beyond them through the analysis of both published and manuscript sources, in the attempt to attain a deeper understanding of the figure of this man, who was a Christian, a military and hydraulic engineer and a political philosopher,. The title of the thesis was chosen to emphasise how, throughout the three years of the doctorate, my research concentrated in equal measure and with the same degree of importance on all the reflections and activities of Jacopo Aconcio. My object, in fact, was to establish how and to what extent the methodological thinking of the intellectual found application in, and at the same time guided, his theoretical and practical production. I did not mention in the title the author’s religious thinking, which has always been considered by everyone the most original and interesting element of his production, because religion, from the Reformation onwards, was primarily a political question and thus it was treated by almost all the authors involved in the Protestant movement - Aconcio in the first place. Even the remarks concerning the private, intimate sphere of faith have therefore been analysed in this light: only by acknowledging the centrality of the “problem of politics” in Aconcio’s theories, in fact, is it possible to interpret them correctly. This approach proves the truth of the theoretical premise to my research, that is to say the unity and orderliness of the author’s thought: in every field of knowledge, Aconcio applies the rules of the methodus resolutiva, as a means to achieve knowledge and elaborate models of pacific cohabitation in society. Aconcio’s continuous references to method can make his writing pedant and rather complex, but at the same time they allow for a consistent and valid analysis of different disciplines. I have not considered the fact that most of his reflections appear to our eyes as strongly conditioned by the time in which he lived as a limit. To see in him, as some have done, the forerunner of Descartes’ methodological discourse or, conversely, to judge his religious theories as not very modern, is to force the thought of an author who was first and foremost a Christian man of his own time. Aconcio repeats this himself several times in his writings: he wants to provide individuals with the necessary tools to reach a full-fledged scientific knowledge in the various fields, and also to enable them to seek truth incessantly in the religious domain, which is the duty of every human being. The will to find rules, instruments, effective solutions characterizes the whole of the author’s corpus: Aconcio feels he must look for truth in all the arts, aware as he is that anything can become science as long as it is analysed with method. Nevertheless, he remains a man of his own time, a Christian convinced of the existence of God, creator and governor of the world, to whom people must account for their own actions. To neglect this fact in order to construct a “character”, a generic forerunner, but not participant, of whatever philosophical current, is a dangerous and sidetracking operation. In this study, I have highlighted how Aconcio’s arguments only reveal their full meaning when read in the context in which they were born, without depriving them of their originality but also without charging them with meanings they do not possess. Through a historical-doctrinal approach, I have tried to analyse the complex web of theories and events which constitute the substratum of Aconcio’s reflection, in order to trace the correct relations between texts and contexts. The thesis is therefore organised in six chapters, dedicated respectively to Aconcio’s biography, to the methodological question, to the author’s engineering activity, to his historical knowledge and to his religious thinking, followed by a last section concerning his fortune throughout the centuries. The above-mentioned complexity is determined by the special historical moment in which the author lived. On the one hand, thanks to the new union between science and technique, the 16th century produces discoveries and inventions which make available a previously unthinkable number of notions and lead to a “revolution” in the way of studying and teaching the different subjects, which, by producing a new form of intellectual, involved in politics but also aware of scientific-technological issues, will contribute to the subsequent birth of modern science. On the other, the 16th century is ravaged by religious conflicts, which shatter the unity of the Christian world and generate theological-political disputes which will inform the history of European states for many decades. My aim is to show how Aconcio’s multifarious activity is the conscious fruit of this historical and religious situation, as well as the attempt of an answer to the request of a new kind of engagement on the intellectual’s behalf. Plunged in the discussions around methodus, employed in the most important European courts, involved in the abrupt acceleration of technical-scientific activities, and especially concerned by the radical religious reformation brought on by the Protestant movement, Jacopo Aconcio reflects this complex conjunction in his writings, without lacking in order and consistency, differently from what many scholars assume. The object of this work, therefore, is to highlight the unity of the author’s thought, in which science, technique, faith and politics are woven into a combination which, although it may appear illogical and confused, is actually tidy and methodical, and therefore in agreement with Aconcio’s own intentions and with the specific characters of European culture in the Renaissance. This theory is confirmed by the reading of the Ars muniendorum oppidorum, Aconcio’s only work which had been up till now unavailable. I am persuaded that only a methodical reading of Aconcio’s works, without forgetting nor glorifying any single one, respects the author’s will. From De methodo (1558) onwards, all his writings are summae, guides for the reader who wishes to approach the study of the various disciplines. Undoubtedly, Satan’s Stratagems (1565) is something more, not only because of its length, but because it deals with the author’s main interest: the celebration of doubt and debate as bases on which to build religious tolerance, which is the best method for pacific cohabitation in society. This, however, does not justify the total centrality which the Stratagems have enjoyed for centuries, at the expense of a proper understanding of the author’s will to offer examples of methodological rigour in all sciences. Maybe it is precisely because of the reforming power of Aconcio’s thought that, albeit often forgotten throughout the centuries, he has never ceased to reappear and continues to draw attention, both as a man and as an author. His ideas never stop stimulating the reader’s curiosity and this may ultimately be the best demonstration of their worth, independently from the historical moment in which they come back to the surface.

Geometria e metodo tra Cartesio e Spinoza

Il testo che segue è, in primo luogo, una lettura del Tractatus de intellectus emendatione di Spinoza. Tra i tanti filtri che potevano caratterizzare la lettura di quest'opera, quello che si è adottato ha avuto lo scopo di far emergere nei suoi tratti fondamentali la distanza tra l'approccio spinoziano al problema della conoscenza e del metodo per il suo raggiungimento e l'approccio cartesiano.

Sistemi per la produzione di enzimi industriali finalizzati alla valorizzazione di scarti agroalimentari

La demolizione idrolitica delle pareti cellulari delle piante tramite enzimi lignocellulosici è quindi uno degli approcci più studiati della valorizzazione di scarti agricoli per il recupero di fitochimici di valore come secondary chemical building block per la chimica industriale. White rot fungi come il Pleurotus ostreatus producono una vasta gamma di enzimi extracellulari che degradano substrati lignocellulosici complessi in sostanze solubili per essere utilizzati come nutrienti. In questo lavoro abbiamo studiato la produzione di diversi tipi di enzimi lignocellulosici quali cellulase, xilanase, pectinase, laccase, perossidase e arylesterase (caffeoilesterase e feruloilesterase), indotte dalla crescita di Pleurotus ostreatus in fermentazione allo stato solido (SSF) di sottoprodotti agroalimentari (graspi d’uva, vinaccioli, lolla di riso, paglia di grano e crusca di grano) come substrati. Negli ultimi anni, SSF ha ricevuto sempre più interesse da parte dei ricercatori, dal momento che diversi studi per produzioni di enzimi, aromi, coloranti e altre sostanze di interesse per l' industria alimentare hanno dimostrato che SSF può dare rendimenti più elevati o migliorare le caratteristiche del prodotto rispetto alla fermentazione sommersa. L’utilizzo dei sottoprodotti agroalimentari come substrati nei processi SSF, fornisce una via alternativa e di valore, alternativa a questi residui altrimenti sotto/o non utilizzati. L'efficienza del processo di fermentazione è stato ulteriormente studiato attraverso trattamenti meccanici di estrusione del substrato , in grado di promuovere il recupero dell’enzima e di aumentare l'attività prodotta. Le attività enzimatiche prodotte dalla fermentazione sono strettamente dipendente della rimozione periodica degli enzimi prodotti. Le diverse matrici vegetali utilizzate hanno presentato diversi fenomeni induttivi delle specifiche attività enzimatiche. I processi SSF hanno dimostrato una buona capacità di produrre enzimi extracellulari in grado di essere utilizzati successivamente nei processi idrolitici di bioraffinazione per la valorizzazione dei prodotti agroalimentari.

Plato's Doctrine Of Forms: Modern Misunderstandings

Among the philosophical ideas of Plato, perhaps the most famous is his doctrine of forms. This doctrine has faced harsh criticism due, in large part, to the interpretations of this position by modern philosophers such as René Descartes, John Locke, and Immanuel Kant. For example, Plato has been interpreted as presenting a ¿two-worlds¿ approach to form and thing and as advancing a rationalist approach to epistemology. His forms have often been interpreted as ideas and as perfect copies of the things of the visible world. In this thesis, I argue that these, along with other interpretations of Plato presented by the moderns, are based on misunderstandings of Plato¿s overall philosophy. In so doing, I attempt to show that the doctrine of forms cannot be directly interpreted into the language of Cartesian, Lockean, and Kantian metaphysics and epistemology, and thus should not be prematurely dismissed because of these modern Platonic interpretations. By analyzing the Platonic dialogues beside the writings of the modern philosophers, I conclude that three of the most prominent modern philosophers, as representatives of their respective philosophical frameworks, have fundamentally misunderstood the nature of Plato¿s famous doctrine of forms. This could have significant implications for the future of metaphysics and epistemology by providing an interpretation of Plato which adds to, instead of contradicts, the developments of modern philosophy.

«Von Menschen und Göttern verlassene Leichname». Totenkult im 'Musée des Monuments Français' (1791-1816)?

Das 'Musée des Monuments Français' ging 1793 aus der Revolution hervor. Das ehemalige Kloster, in dem enteignete Kirchengüter gelagert wurden, mutierte unter Alexandre Lenoir zu einer chronologisch geordneten Ruhmesstätte der französischen Geschichte. Grabmäler und Monumente erinnern an verschiedene Personen dieser Geschichte – von Héloïse über viele Könige bis hin zu Descartes. Allerdings war das 'Musée des Monuments Français' weniger ein Ort des royalen Totenkults als vielmehr ein Museum, in dem auch die königlichen Grabmäler als Exponate innerhalb der Präsentation der französischen Geschichte fungierten. Daher führte es unter Zeitgenossen zu einer Polarisierung in Anhänger und Gegner: So waren zum Beispiel Michelet und Wilhelm von Humboldt vom 'Musée des Monuments Français' begeistert, während Chateaubriand es strikt ablehnte. Im 'Musée des Monuments Français’ waren die Grabstätten und Skulpturen permanente Zeugnisse der Niederlage des Königtums. In der Restauration wurde das Museum Ende 1816 geschlossen, die königlichen Grabmäler wurden zurück in die Kirche von Saint Denis überführt.

William Harvey revisited

William Harvey's discovery of the circulation of the blood is often described as a product of the Scientific Revolution of the Seventeenth Century. Modern research has, however, shown thatHarvey followed the Aristotelian research tradition and thus tried to reveal the purpose of the organs through examination of various animals. His publication of 1628 has to be read as an argument of natural philosophy, or, more precisely, as a series of linked observations, experiments and philosophical reasonings from which the existence of circulation has to be deduced as a logical consequence. Harvey did not consider experiments as superior to philosophical reasoning nor intended he to create a new system of medicine. He believed in the vitality of the heart and the blood and rejected Francis Bacon's empirism and the mechanistic rationalism of Descartes. Harvey's contribution and originality lied less in his single observations and experiments but in the manner how he linked them with critical reasoning and how he accepted, presented and defended the ensuing radical findings.

Samaja, Juan. Epistemología y metodología. Elementos para una teoría de la investigación científica. 3ª edición, 6ª reimpresión. Buenos Aires, EUDEBA, 2005, 414 p.

Fil: Fischetti, Natalia.

Luces y sombras de la modernidad en la ciencia política

El presente trabajo se plantea analizar el concepto moderno de ciencia para comprender las luces y sombras que proyecta en el campo de la investigación en ciencias sociales en general y en la ciencia política en particular. En este sentido, nos preguntamos ¿cuál es la concepción de ciencia que impera en el pensamiento de los autores clásicos analizados? ¿Cómo estos autores conciben la conexión entre ciencia y acción política? ¿Cuáles son los principales debates epistemológicos que enfrenta la ciencia política de nuestro tiempo? En virtud de estos interrogantes, se construye la siguiente hipótesis: es necesario replantear algunos elementos del paradigma científico de la modernidad para poder abordar mejor los nuevos problemas de la ciencia política. Esta posición nos lleva a reflexionar sobre los desafíos que enfrentamos los cientistas políticos actuales y las similitudes y/o diferencias que tenemos con nuestros colegas del pasado. La metodología de investigación se funda en el análisis comparado de algunas obras clásicas de Aristóteles, Maquiavelo, Descartes, Hobbes, Kant, Tocqueville, Weber y Arendt.

Geometría analítica : para ciencias e ingenierías

Durante siglos, la geometría y el álgebra se fueron desarrollando como disciplinas matemáticas diferentes. El filósofo y matemático francés René Descartes, publicó en el año 1637 su tratado La Géométrie en el que introdujo un método para unir esas dos ramas de la matemática, llamado Geometría Analítica, basado en el uso de sistemas coordenados, por medio de los cuales, los procesos algebraicos se pueden aplicar al estudio de la geometría. La Geometría Analítica permite hallar y estudiar los lugares geométricos de forma sistemática y general. Provee de métodos para transformar los problemas geométricos en problemas algebraicos, resolverlos analíticamente e interpretar geométricamente los resultados. Geometría Analítica para Ciencias e Ingenierías, es un texto cuyo principal objetivo es acompañar el proceso de enseñanza y aprendizaje de un curso de Geometría analítica de nivel universitario de grado, promoviendo en el estudiante el desarrollo de habilidades de observación, comparación, análisis, síntesis e integración de conceptos tanto de la Geometría Analítica plana como de la espacial. Los contenidos que se estudian en este texto tienen gran variedad de aplicaciones en investigaciones matemáticas, en astronomía, física, química, biología, ingeniería, economía, entre otros. El texto se encuentra dividido en 5 capítulos, cada uno de los cuales cuenta con el desarrollo de contenidos teóricos, ejercicios y problemas de aplicación.