The Regulation of AMD Pathobiology by Complement Factor H

Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/- and Cfh-/- mice fed a high fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (RPE) deposit formation, specifically basal laminar deposits, following high fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/- and Cfh-/- mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/- mice. We demonstrate that such pathology is a function of excess complement activation and C5a production, associated with monocyte recruitment, in Cfh+/- mice versus complement deficiency in Cfh-/- animals. Due to the CFH dependent increase in sub-RPE deposit height we interrogated the potential of CFH as a novel regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Interestingly, although the CFH H402 variant shows altered binding to BrM, this does not affect its ability to remove endogenous lipoproteins. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD.

Fatores críticos de sucesso das empresas familiares: uma abordagem competitiva

The present objective study to inside identify the critical factors of success of the local family companies of a competitive boarding. For in such a way the same it understands the culture and the management of the family companies of success, identifies the essential areas of performance, it establishes the restrictive factors of the success, and analyzes the level of influence of the critical factors of success in the competitiveness of this type of company. In function of the subject little to be explored, and of this study to provide a general vision concerning the factors that take the family companies to get success, this research is explorer. On the other hand, for describing characteristic of the familiar companies in prominence in the local scene and for being worried about the practical performance, the same one also is descriptive. The sample in turn is the not-probabilist one of the intentional type, for accessibility. For operacionalization of the collection of data, the direct contact was used, being the composed instrument of research for variable as management, culture, critical factors of success and competitiveness. The study it evidences that in regards to the management and the culture of the family companies of success, some variable are turned aside from the standard of the conventional family companies cited by literature. Of general form in the familiar companies of success it has a bigger level of professionalization of the management. As for the value given to the knowledge, the study sample that the conventional family companies give little importance to it, in contrast of the family companies in prominence, who value of significant form the search for the knowledge. He is demonstrated despite the family companies of success, even so total are not professionalized, possess a bigger level of professionalization of the management, ratifying of certain forms the reason for which the majority develops the Strategical Planning formal periodically. In short, the results point 17 critical factors of success with respect to the family companies, in special factors as the product quality and services, and the use of the technology

Globale Entwikclung als Lernbereich in den Naturwissenschaften

Mit dem Orientierungsrahmen für den Lernbereich Globale Entwicklung wurden Anregungen gegeben, die Themen nachhaltige Entwicklung und globale Entwicklung im Unterricht in allen Schulfächern aufzugreifen. Die drei naturwissenschaftlichen Schulfächer Biologie, Chemie und Physik haben sich bislang sehr unterschiedlich auf das Thema eingelassen. In der Biologiedidaktik finden sich sowohl Forschungsarbeiten als auch Unterrichtsvorschläge; für Chemie und insbesondere Physik existieren hingegen nur sehr wenige Ansätze. Im Rahmen der zu erwerbenden Bewertungskompetenz, wie sie durch die Bildungsstandards in den Fächern Biologie, Chemie und Physik beschrieben wird, ist nachhaltige Entwicklung als ein mögliches Thema, ein Kontext anzusehen. Vor diesem größeren Hintergrund wird die gängige unterrichtspraktische Literatur in allen drei Fächern exemplarisch zusammengefasst. (DIPF/Orig.)

Fatores críticos de sucesso das empresas familiares: uma abordagem competitiva

The present objective study to inside identify the critical factors of success of the local family companies of a competitive boarding. For in such a way the same it understands the culture and the management of the family companies of success, identifies the essential areas of performance, it establishes the restrictive factors of the success, and analyzes the level of influence of the critical factors of success in the competitiveness of this type of company. In function of the subject little to be explored, and of this study to provide a general vision concerning the factors that take the family companies to get success, this research is explorer. On the other hand, for describing characteristic of the familiar companies in prominence in the local scene and for being worried about the practical performance, the same one also is descriptive. The sample in turn is the not-probabilist one of the intentional type, for accessibility. For operacionalization of the collection of data, the direct contact was used, being the composed instrument of research for variable as management, culture, critical factors of success and competitiveness. The study it evidences that in regards to the management and the culture of the family companies of success, some variable are turned aside from the standard of the conventional family companies cited by literature. Of general form in the familiar companies of success it has a bigger level of professionalization of the management. As for the value given to the knowledge, the study sample that the conventional family companies give little importance to it, in contrast of the family companies in prominence, who value of significant form the search for the knowledge. He is demonstrated despite the family companies of success, even so total are not professionalized, possess a bigger level of professionalization of the management, ratifying of certain forms the reason for which the majority develops the Strategical Planning formal periodically. In short, the results point 17 critical factors of success with respect to the family companies, in special factors as the product quality and services, and the use of the technology

Melhoramento genético florestal e o desafio imposto pela doença da murchidão do pinheiro

Mestrado em Engenharia Florestal e dos Recursos Naturais - Instituto Superior de Agronomia - UL

Coartación aórtica

Las teorías propuestas en la fisiopatología de la CA incluyen: 1) En el periodo prenatal el flujo eyectado por el ventrículo izquierdo continua por las ramas del cayado aórtico y el del ventrículo derecho pasa a la aorta descendente a través del conducto arteriovenoso, con disminución de irrigación del istmo y alteración secundaria del calibre. 2) Patrones de migración anormales del desarrollo del arco, que ocasionan una hipoplasia tubular del istmo.