Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.

Características Biológicas de la Recuperación Hematopoyética en Pacientes sometidos a Trasplante de Sangre de Cordón Umbilical

En la medul.la òssia (MO) de pacients sotmesos a trasplantament de sang de cordó umbilical (TSCU) es veu, en ocasions, un augment de precursors limfoides B que poden semblar blasts, plantejant-se el diagnòstic diferencial amb una recidiva leucèmica. L´objectiu d´aquest estudi ha sigut estudiar la incidència del augment de cèl•lules blàstiques no leucèmiques en MO després del TSCU. La incidència acumulada a 1 any del augment de blasts no leucèmics va ser del 26.1% i aquest augment es va relacionar amb una baixa tassa de malaltia d'empelt contra hoste aguda i crònica.

Desenvolupament d'hidrogels superficials que contenen motius d'adhesió cel·lular

Projecte de recerca elaborat a partir d’una estada al Departament d’Enginyeria Química del Massachusetts Institute of Technology entre abril i octubre del 2006. S’ha dissenyat i sintetitzat uns nous films polimèrics, amb aplicacions en l’àmbit de l’enginyeria de teixits, utilitzant la tècnica anomenada iCVD (initiated Chemical Vapor Deposition), prèviament desenvolupada pel grup receptor. Es tracta d’uns hidrogels superficials de gruix controlable, que incorporen un monòmer fluorat, el qual s’havia estudiat extensament en el grup d’origen. Aquest monòmer es caracteritza per reaccionar molt fàcilment amb pèptids, de manera que aquests queden units covalentment a la superfície. Diferents estratègies pel desenvolupament d’aquests copolímers han estat avaluades, tant des del punt de vista purament sintètic com de la pròpia aplicació. Les condicions de polimerització han estat optimitzades i els hidrogels s’han caracteritzat químicament per tècniques espectroscòpiques (FTIR, XPS), i físicament per angle de contacte i el·lipsometria. D’aquesta manera, s’ha estudiat la capacitat dels hidrogels d’absorbir aigua i alhora augmentar el seu gruix, depenent de la quantitat d’agent reticulant introduït i de la incorporació del nou monòmer. A continuació, s’han optimitzat les condicions de reacció d’aquestes superfícies amb pèptids que incorporen una molècula fluorescent, la qual permet detectar fàcilment per microscòpia de fluorescència si la reacció ha tingut lloc. Una vegada la plataforma ha estat posada a punt, s’han iniciat assajos cel·lulars tant amb fibroblasts embriònics de ratolí com amb cèl·lules humanes umbilicals. Els resultats preliminars suggereixen una morfologia diferent de les cèl·lules segons si es cultiven sobre films modificats amb pèptids que promouen l’adhesió cel·lular o sobre les seves seqüències permutades no actives. Però, el més interessant és que també s’han observat certes diferències depenent si els films contenen el component hidrogel o no, fet que suggeriria un paper actiu d’aquests noves superfícies en el comportament cel·lular.

Research and teaching: a holy or an unholy alliance?

Much of the self-image of the Western university hangs on the idea that research and teaching are intimately connected. The central axiom here is that research and teaching are mutually supportive of each other. An institution lacking such a set of relationships between research and teaching falls short of what it means to be a university. This set of beliefs raises certain questions: Is it the case that the presence of such a mutually supportive set of relationships between research and teaching is a necessary condition of the fulfilment of the idea of the university? (A conceptual question). And is it true that, in practice today, such a mutually supportive set of relationships between research and teaching characterises universities? (An empirical question). In my talk, I want to explore these matters in a critical vein. I shall suggest that: a) In practice today, such a mutually supportive set of relationships between research and teaching is in jeopardy. Far from supporting each other, very often research and teaching contend against each other. Research and teaching are becoming two separate ideologies, with their own interest structures. b) Historically, the supposed tight link between research and teaching is both of recent origin and far from universally achieved in universities. Institutional separateness between research and teaching is and has been evident, both across institutions and even across departments in the same institution. c) Conceptually, research and teaching are different activities: each is complex and neither is reducible to the other. In theory, therefore, research and teaching may be said to constitute a holy alliance but in practice, we see more of an unholy alliance. If, then, in an ideal world, a positive relationship between research and teaching is still a worthwhile goal, how might it be construed and worked for? Seeing research and teaching as two discrete and unified sets of activity is now inadequate. Much better is a construal of research and teaching as themselves complexes, as intermingling pools of activity helping to form the liquid university that is emerging today. On this view, research and teaching are fluid spaces, ever on the move, taking up new shapes, and themselves dividing and reforming, as the university reworks its own destiny in modern society. On such a perspective, working out a productive relationship between research and teaching is a complex project. This is an alliance that is neither holy nor unholy. It is an uneasy alliance, with temporary accommodations and continuous new possibilities.

Inequality across countries in energy intensities: an analysis of the role of energy transformation and final energy consumption

This paper analyzes the role of the energy transformation index and of final energy consumption per GDP unit in the disparities in energy intensity across countries. In that vein, we use a Theil decomposition approach to analyze global primary energy intensity inequality as well as inequality across different regions of the world and inequality within these regions. The paper first demonstrates the pre-eminence of divergence in final energy consumption per GDP unit in explaining global primary energy intensity inequality and its evolution during the 1971-2006 period. Secondly, it shows the lower (albeit non negligible) impact of the transformation index in global primary energy inequality. Thirdly, the relevance of regions as unit of analysis in studying crosscountry energy intensity inequality and their explanatory factors is highlighted. And finally, how regions around the world differ as to the relevance of the energy transformation index in explaining primary energy intensity inequality.

Hospital Universitari Vall d'Hebron. Institut de Recerca

En los transplantes de progenitores hematopoyéticos, la sangre de cordón umbilical es una fuente establecida de células madre hematopoyéticas que presenta como mayor ventaja una menor incidencia de enfermedades de injerto contra el huésped. Sin embargo, el bajo número de células madre obtenidas de una sola unidad limita su utilización a un número reducido de pacientes. Las células madre hematopoyéticas se definen por su capacidad de automantenimiento y reconstitución de todo el sistema hematopoyético de un huésped trasplantado. En ratón, la combinación de los marcadores de superficie Lin- LSK junto con los marcadores de la familia SLAM, ha permitido establecer una jerarquía en las poblaciones de células madre y progenitores hematopoyéticos. Sin embargo, la población de células madre hematopoyéticas humanas CD34+CD38- es heterogénea y las subpoblaciones de progenitores y células madre no están bien establecidas. Uno de los objetivos de este trabajo es determinar si los marcadores de la familia SLAM podrían redefinir la población de células madre hematopoyéticas humanas CD34+CD38- de forma similar a lo sucedido en ratón. En este trabajo se describe una nueva población de progenitores hematopoyéticos en sangre de cordón umbilical caracterizada por el fenotipo CD34+CD38-CD150+CD135-. Lon ensayos realizados tanto in vitro como in vivo han demostrado que esta población esta formada por células con capacidad de autorrenovación, de diferenciación a todos los linajes hematopoyéticos, y de reconstitución a corto y largo plazo de un modelo murino inmunodeficiente irradiado. Por otro lado, con la finalidad de obtener un número suficiente de progenitores hematopoyéticos para ser trasplantados, se han estudiado diferentes sistemas de expansión in vitro. Se ha observado que el ácido valproico (un inhibidor de las histona deacetilasas) y la activación de la vía de Notch, promueven el mantenimiento y expansión de los progenitores hematopoyéticos reduciendo los procesos de diferenciación.