Surface assembly of poly(I:C) on PEGylated microspheres to shield from adverse interactions with fibroblasts.

By expressing an array of pattern recognition receptors (PRRs), fibroblasts play an important role in stimulating and modulating the response of the innate immune system. The TLR3 ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), a mimic of viral dsRNA, is a vaccine adjuvant candidate to activate professional antigen presenting cells (APCs). However, owing to its ligation with extracellular TLR3 on fibroblasts, subcutaneously administered poly(I:C) bears danger towards autoimmunity. It is thus in the interest of its clinical safety to deliver poly(I:C) in such a way that its activation of professional APCs is as efficacious as possible, whereas its interference with non-immune cells such as fibroblasts is controlled or even avoided. Complementary to our previous work with monocyte-derived dendritic cells (MoDCs), here we sought to control the delivery of poly(I:C) surface-assembled on microspheres to human foreskin fibroblasts (HFFs). Negatively charged polystyrene (PS) microspheres were equipped with a poly(ethylene glycol) (PEG) corona through electrostatically driven coatings with a series of polycationic poly(L-lysine)-graft-poly(ethylene glycol) copolymers, PLL-g-PEG, of varying grafting ratios g from 2.2 up to 22.7. Stable surface assembly of poly(I:C) was achieved by incubation of polymer-coated microspheres with aqueous poly(I:C) solutions. Notably, recognition of both surface-assembled and free poly(I:C) by extracellular TLR3 on HFFs halted their phagocytic activity. Ligation of surface-assembled poly(I:C) with extracellular TLR3 on HFFs could be controlled by tuning the grafting ratio g and thus the chain density of the PEG corona. When assembled on PLL-5.7-PEG-coated microspheres, poly(I:C) was blocked from triggering class I MHC molecule expression on HFFs. Secretion of interleukin (IL)-6 by HFFs after exposure to surface-assembled poly(I:C) was distinctly lower as compared to free poly(I:C). Overall, surface assembly of poly(I:C) may have potential to contribute to the clinical safety of this vaccine adjuvant candidate.

Nuclear factor I-C regulates TGF-{beta}-dependent hair follicle cycling.

Skin appendages such as teeth and hair share several common signaling pathways. The nuclear factor I C (NFI-C) transcription factor has been implicated in tooth development, but a potential role in hair growth had not been assessed. In this study we found that NFI-C regulates the onset of the hair growth cycle. NFI-C(-/-) mice were delayed in the transition from the telogen to anagen phase of the hair follicle cycle after either experimental depilation or spontaneous hair loss. Lack of NFI-C resulted in delayed induction of the sonic hedgehog, Wnt5a, and Lef1 gene expression, which are key regulators of the hair follicle growth initiation. NFI-C(-/-) mice also showed elevated levels of transforming growth factor β1 (TGF-β1), an inhibitor of keratinocyte proliferation, and of the cell cycle inhibitor p21 at telogen. Reduced expression of Ki67, a marker of cell proliferation, was noted at the onset of anagen, indicating impaired activation of the hair progenitor cells. These findings implicate NFI-C in the repression of TGF-β1 signaling during telogen stage, resulting in the delay of progenitor cell proliferation and hair follicle regeneration in NFI-C-deficient mice. Taken together with prior observations, these findings also designate NFI-C as a regulator of adult progenitor cell proliferation and of postnatal tissue growth or regeneration.

El Rol del pedagog i les funcions que desenvolupa en els processos d'adopció internacional

L’adopció internacional ha passat a ocupar un lloc important en el nostre context social, polític i educatiu i, com a pedagogs experts en l’àmbit, volem reflexionar, entorn de la importància d’aquesta figura professional en els equips interdisciplinaris que treballen amb les famílies i la infància adoptada i entorn de la seva implicació en les diferents etapes del procés d’adopció. Per presentar aquest perfil professional fem un recorregut per les diferents funcions que desenvolupa, tant durant el període preadoptiu, com en el postadoptiu, destacant la formació a famílies i professionals, la seva participació en el procés de valoració dels sol·licitants d’adopció i la intervenció en els processos d’orientació i assessorament postadoptiu.

El món rural i urbà en la Lleida islàmica (S. XI-XII): Lleida i l'est del districte: Castelldans i el pla del Mascançà

Lleida i el seu territori s’integraren a Alandalús des del 713-714 fins al 1149. Durant aquest període força dilatat en la història, una civilització, la islàmica, ocupà i explotà el pai-satge que avui coneixem com les comarques del pla de Lleida. Certament, la seva empremta és ben visible en forma de to-pònims, fortaleses, eixos viaris, regadius, aliments i vocables que avui encara són usats. A més, si cal destacar una carac-terística de la societat islàmica lleidatana és la seva capacitat d’adaptar-se al medi natural i transformar-lo d’acord amb les seves necessitats culturals. Aquest llibre presenta les hipòtesis i conclusions de la recerca focalitzada en l’estudi del món urbà i rural islàmic del distric-te andalusí de Lleida. Concretament, s’ha centrat l’atenció a estudiar l’àrea de Castelldans i el pla del Mascançà.

“La lliga dels magnats”. La Premier League i el negoci del futbol en l’era dels mitjans globals

The relationship between the mass media and sport has reached a state of symbiosis. The great media companies and sports organizations have combined synergies to get the best return on their products, both communicationrelated and sports-related. To define this situation, some authors have spoken of the “new sport oligopoly” or of the “global media sports complex”. This article analyzes the formation of this complex based on real examples of financial relations between media companies and sports organizations and, finally, draws attention to how these relations took place in the Premier League during the 2009-2010 season, taking into account the fact that this was the European football league which consolidated the process of international commercialization the soonest, which has the most highly valued football brand (Manchester United) and which has the clubs that make the most money from television rights and commercials.

Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration.

BACKGROUND & AIMS: Knockout studies of the murine Nuclear Factor I-C (NFI-C) transcription factor revealed abnormal skin wound healing and growth of its appendages, suggesting a role in controlling cell proliferation in adult regenerative processes. Liver regeneration following partial hepatectomy (PH) is a well-established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although NFI-C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether NFI-C may play a role in hepatocyte proliferation and liver regeneration. METHODS: Liver regeneration and cell proliferation pathways following two-thirds PH were investigated in NFI-C knockout (ko) and wild-type (wt) mice. RESULTS: We show that the absence of NFI-C impaired hepatocyte proliferation because of plasminogen activator I (PAI-1) overexpression and the subsequent suppression of urokinase plasminogen activator (uPA) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI-C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of NFI-C, as can be explained by a self-regulatory feedback loop with transforming growth factor beta 1 (TGF-ß1), may limit the number of hepatocytes entering the first wave of cell division and/or prevent late initiations of mitosis. CONCLUSION: NFI-C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.

Cahiers du bolchévisme : organe théorique du Parti communiste français (S.F.I.C.)

1925/01/09 (A1,N8).

Cahiers du bolchévisme : organe théorique du Parti communiste français (S.F.I.C.)

1926/08/15 (A2,N55).

Cahiers du bolchévisme : organe théorique du Parti communiste français (S.F.I.C.)

1934/09/15 (A11,N18).

Cahiers du bolchévisme : organe théorique du Parti communiste français (S.F.I.C.)

1935/11/01 (A12,N22).

Cahiers du bolchévisme : organe théorique du Parti communiste français (S.F.I.C.)

1941/04 (A18)-1941/09.