Mechanisms of Ligand–Protein Interaction in Sec-14-like Transporters Investigated by Computer Simulations

We review our recent work on protein-ligand interactions in vitamin transporters of the Sec-14-like protein. Our studies focused on the cellular-retinaldehyde binding protein (CRALBP) and the alpha-tocopherol transfer protein (alpha-TTP). CRALBP is responsible for mobilisation and photo-protection of short-chain cis-retinoids in the dim-light visual cycle or rod photoreceptors. alpha-TTP is a key protein responsible for selection and retention of RRR-alpha-tocopherol, the most active isoform of vitamin E in superior animals. Our simulation studies evidence how subtle chemical variations in the substrate can lead to significant distortion in the structure of the complex, and how these changes can either lead to new protein function, or be used to model engineered protein variants with tailored properties. Finally, we show how integration of computational and experimental results can contribute in synergy to the understanding of fundamental processes at the biomolecular scale.

Complication sévère d’une contention collée linguale mandibulaire

Le collage d’un fil torsadé souple sur les faces linguales des six dents antérieures mandibulaires est une modalité de contention couramment utilisée. Les complications sont rares mais peuvent être assez sérieuses pour provoquer des dégâts biologiques. Cet article présente une complication sérieuse d’un fil de contention torsadé souple, collé en lingual. Quatre ans après son traitement orthodontique, un homme de 20 ans a consulté pour la rupture d’un fil de contention torsadé souple. L’examen clinique a montré un torque radiculo-vestibulaire d’environ 35° d’une dent. Une image en tomographie volumique à faisceau conique (Cone-Beam Computed Tomography ou CBCT) a montré que la racine et l’apex de la dent étaient presque totalement hors de l’os du côté vestibulaire. Étonnamment, la vitalité de la dent était préservée. La dent a été ramenée presque jusqu’à sa position initiale; cliniquement, seule une récession gingivale a persisté. Les orthodontistes et les dentistes devraient être conscients des complications possibles des contentions collées. Les patients devraient être clairement informés de la manière dont les problèmes peuvent être détectés à un stade précoce.

CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture.

Release of chemotactic factors in response to tissue damage has been described for different musculoskeletal tissues, including the intervertebral disc (IVD). This study investigated the chemoattractants that are released by induced degenerative IVDs and may be involved in recruiting mesenchymal stem cells (MSCs). Bovine caudal discs were cultured within a bioreactor and loaded under conditions that mimicked physiological or degenerative settings. Between days 4-6, medium was replaced by PBS, which was subsequently used for proteomic, ELISA and immunoprecipitation analyses of secreted chemokines and cytokines. A Boyden chamber assay was used to observe human MSC migration towards native and chemokine depleted media. Gene expression levels of chemokine receptors in human MSCs were analysed, and CCL5 was localised in bovine and human IVD by immunohistochemistry. Proteomic analysis revealed the presence of CCL5 and CXCL6 within conditioned media. Higher concentrations of CCL5 were found in the degenerative media, and a relationship was found between interleukin-1β and CCL5 concentration. Chemokine immunoprecipitation showed that MSCs had a significantly reduced chemotactic migration towards CCL5-immunoprecipitated and CCL5/CXCL6 co-immunoprecipitated media, whilst CXCL6 depletion did not change MSC chemotaxis. MSCs showed a significant increase in mRNA expression of the CCL5 receptors, CCR1 and CCR4, upon culture in degenerative media. Furthermore, CCL5 was identified in bovine and human disc tissue by immunohistochemistry. Hence, CCL5 may be a key chemoattractant that is produced and released by the intervertebral disc cells. Therefore, these factors could be used to enhance stem/progenitor cell mobilisation in regenerative therapies for early stages of disc degeneration.

In Search of Political Influence: Strategic Choices and Media Coverage of Political Parties, Interest Groups and Social Movements in Western European Countries

Outside lobbying is a key strategy for social movements, interest groups and political parties for mobilising public opinion through the media in order to pressure policymakers and influence the policymaking process. Relying on semi-structured interviews and newspaper content analysis in six Western European countries, this article examines the use of four outside lobbying strategies – media-related activities, informing (about) the public, mobilisation and protest – and the amount of media coverage they attract. While some strategies are systematically less pursued than others, we find variation in their relative share across institutional contexts and actor types. Given that most of these differences are not accurately mirrored in the media, we conclude that media coverage is only loosely connected to outside lobbying behaviour, and that the media respond differently to a given strategy when used by different actors. Thus, the ability of different outside lobbying strategies to generate media coverage critically depends on who makes use of them.

APS-Inserateanalyse der eidgenössischen Abstimmungen vom 9. Februar 2014

Die vorliegende APS-Inserateanalyse beschäftigt sich mit den eidgenössischen Abstimmungen vom 9. Februar 2014. Im ersten Kapitel werden die drei Vorlagen (FABI, Volksinitiative zur Abtreibungsfinanzierung und Masseneinwanderungsinitiative) hinsichtlich allgemeiner Kriterien miteinander verglichen. Dabei werden zunächst mit der Intensität und der Ausrichtung der verschiedenen Inseratekampagnen die zwei Hauptindikatoren präsentiert. An-schliessend erfolgt die Analyse der Platzierung der Anzeigen nach Pressegattungen sowie zeitlichen und geografischen Aspekten. In den Kapiteln 2-4 stehen vorlagenspezifische Eigenschaften im Vordergrund. In einem ersten Schritt werden für jede Vorlage die meist verwendeten Inseratetypen vorgestellt. Danach wird auf den Inhalt sowie auf die AbsenderInnen der Hauptbotschaften eingegangen. Falls es die Anzahl der verfügbaren Inserate erlaubt, werden drittens die Determinanten der zentralen Botschaften mit Hilfe von statistischen Verfahren unter die Lupe genommen. Für die Masseneinwanderungsinitiative (Kapitel 4) wurde eine ausführliche Spezialanalyse durchgeführt, mit der die Kampagnen der beiden Lager nach spezifischer Mobilisierung untersucht werden. Das fünfte Kapitel schliesst mit einem Fazit.