Characterizing Complex Polysera Produced by Antigen-Specific Immunization through the Use of Affinity-Selected Mimotopes

BACKGROUND: Antigen-based (as opposed to whole organism) vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS: Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes) can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets. CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines

Anchored Design of Protein-Protein Interfaces

Few existing protein-protein interface design methods allow for extensive backbone rearrangements during the design process. There is also a dichotomy between redesign methods, which take advantage of the native interface, and de novo methods, which produce novel binders.Here, we propose a new method for designing novel protein reagents that combines advantages of redesign and de novo methods and allows for extensive backbone motion. This method requires a bound structure of a target and one of its natural binding partners. A key interaction in this interface, the anchor, is computationally grafted out of the partner and into a surface loop on the design scaffold. The design scaffold's surface is then redesigned with backbone flexibility to create a new binding partner for the target. Careful choice of a scaffold will bring experimentally desirable characteristics into the new complex. The use of an anchor both expedites the design process and ensures that binding proceeds against a known location on the target. The use of surface loops on the scaffold allows for flexible-backbone redesign to properly search conformational space.This protocol was implemented within the Rosetta3 software suite. To demonstrate and evaluate this protocol, we have developed a benchmarking set of structures from the PDB with loop-mediated interfaces. This protocol can recover the correct loop-mediated interface in 15 out of 16 tested structures, using only a single residue as an anchor

La Haute école spécialisée de Suisse Occidentale (HES-SO) : démarche chaotique ou politique publique planifiée ?

Adoptée en 1995, la nouvelle loi fédérale sur les Hautes écoles spécialisées (HES) a pour objectif le renforcement des liens de ce secteur de formation avec le marché du travail, afin d'accroître la capacité concurrentielle de la place économique suisse. De nouvelles tâches leur sont confiées en matière de recherche et de développement, de prestations à des tiers et de cours post-grades. Dans ce but, sept HES sont homologuées en Suisse, ce qui correspond à une gestion inédite visant à concentrer les filières de formation dans des centres de compétences régionaux. Les auteurs étudient le cas de la Haute école spécialisée de Suisse occidentale (HES-SO) entre 1995 et 2001, sous l'angle plus précis du plan d'action. Loin de constituer une démarche planifiée, les résultats montrent que l'opération correspondante de priorisation des actes de mise en oeuvre n'est réalisée que très partiellement et conduit à des déficits et des décalages par rapport aux objectifs d'origine du Conseil fédéral. L'explication réside à la fois dans le jeu des acteurs cantonaux, dans le manque de certaines ressources (consensus, temps, légitimité démocratique) et dans la position inconfortable des HES dans l'environnement fédéraliste suisse. Toutefois, si les HES sont coincées, pour l'instant, entre les échelons cantonaux et fédéraux, cette politique publique pourrait en définitive constituer un préambule à un redécoupage territorial de la Suisse en régions

The palliative treatment of bronchial carcinoma with lasertherapy and stent.

Institute of Clinical Surgery IV, La Sapienza, University of Rome, Italy

Giant mesenteric fibromatosis.

Mesenteric fibromatosis is a proliferative fibroblastic neoplasia of the small intestine mesentery which may occur as a unique or multiple formation. Mesenteric fibromatosis represents the 8% of all desmoid neoplasm. Giant mesenteric fibromatosis is uncommon by itself (2-4 case/milion/year). Since the rarity of this tumor and the difficulties in diagnostic and therapeutic ambit, we believe it justified to describe a case of giant mesenteric fibromatosis which came to our observation

A rare case of pulmonary neurofibroma: Clinical and diagnostic evaluation and surgical treatment

The authors report a rare case of a pulmonary neurofibroma treated by surgical excision. The case report is accompanied by a review of the literature and the discussion of the diagnostic problems posed by neurogenic tumors of the thorax