Friedrich G. Habel, Brustbild

Signatur des Originals: S 36/F00665

Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif.

Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.

Malaria vaccines - The long synthetic peptide approach: Technical and conceptual advancements.

This review describes the advances in malaria antigen discovery and vaccine development using the long synthetic peptide platforms that have been made available during the past 5 years. The most recent technical developments regarding peptide synthesis with the optimized production of large synthetic fragments are discussed. Clinical trials of long synthetic peptides are also reviewed. These trials demonstrated that long synthetic peptides are safe and immunogenic when formulated with various adjuvants. In addition, long synthetic peptides can elicit an antibody response in humans and have demonstrated inhibitory activity against parasite growth in vitro. Finally, new approaches to exploit the abundance of genomic data and the flexibility and speed of peptide synthesis are proposed.

La ville par-delà ses frontières : la représentation de Paris chez Mohammed Dib, Abdelwahab Meddeb et Annie Cohen

Au cours des décennies 1970 et 1980, alors que le statut des immigrants et la question de leur intégration alimentent débats et controverses en France, trois écrivains proposent chacun le récit d’un Maghrébin vivant à Paris qui interroge la société et dénonce ses dysfonctionnements. Ce mémoire vise à montrer l’apport de Mohammed Dib (Habel, 1977), d’Abdelwahab Meddeb (Phantasia, 1986) et d’Annie Cohen (L’Édifice invisible, 1988) aux représentations nouvelles de la capitale apparues dans l’imaginaire social depuis la décolonisation. Face à la suprématie de la culture française, les protagonistes proposent une ouverture radicale à l’altérité et questionnent les processus d’aliénation et de renforcement du statu quo identitaire et culturel. Une modalité d’écriture commune aux romans à l’étude, la promenade conduit les trois auteurs à travailler sur la mise en forme du récit tout en plaçant les héros en opposition face à l’évolution urbaine et la société occidentale consumériste.

Étude de protection conférée par vaccination ADN dans un modèle murin d’hépatite auto-immune

La vaccination ADN à l’aide de plasmides codant pour des autoantigènes s’est avérée efficace dans la protection contre plusieurs maladies auto-immunes. Le but de ce mémoire était dans un premier temps d’établir si un protocole de vaccination ADN composé de 3 injections de pCMV-CTLA-4-NP et de pVR-IL-12 à deux semaines d’intervalle avait un effet protecteur contre le développement d’une hépatite auto-immune chez la souris TTR-NP, un modèle murin transgénique de la maladie et précédemment développé au laboratoire. Dans un deuxième temps, le but était d’élucider, le cas échéant, les mécanismes sous-tendant la protection conférée par la vaccination ADN. Les hypothèses initiales étaient qu’une protection allait effectivement être conférée par la vaccination ADN et que celle-ci pouvait être attribuable à une déviation de la réponse typiquement Th1 de la maladie vers une réponse Th2, à un épuisement des cellules immunitaires et/ou à l’activation et à l’induction de prolifération de cellules régulatrices. Les résultats montrent que la vaccination ADN induit une protection transitoire contre le développement d’infiltrations lymphocytaires au foie. Cette protection se ferait via un épuisement des cellules CD4+, CD8+ et CD19+ se retrouvant à la rate et exprimant PD 1 dans une plus forte proportion à 3 mois, et ne serait médiée ni par les lymphocytes T régulateurs CD4+CD25+FoxP3+, ni par les cellules CD8+FoxP3+. Une déviation de la réponse Th1 vers une réponse Th2 demeure une explication supplémentaire plausible à la protection conférée mais nécessiterait une caractérisation en situation plus physiologique avant de pouvoir inférer sur son implication réelle. La vaccination ADN n’influe ni sur la présence d’autoanticorps, ni sur les niveaux d’alanine aminotransférase, deux marqueurs de la maladie.

Der Tempel zu Jerusalem während des letzten Jahrhunderts seines Bestandes nach Josephus

von F. Spiess

Calcareous dinoflagellates in Cretaceous to Recent sediments of DSDP Hole 39-356

Calcareous dinoflagellates often dominate the dinoflagellate cyst assemblage in Cretaceous to Recent oceanic sediments. However, their distribution in Paleogene sediments has scarcely been studied. The investigation of samples from DSDP Site 356 for their calcareous dinoflagellate content revealed 35 mainly long-ranging taxa. The associations and characteristic wall types (pithonelloid, oblique, radial, tangential) fluctuate quantitatively and qualitatively in distinct stratigraphic patterns. Significant shifts, primarily at the K/T boundary and the Paleocene/Eocene boundary, reflect changes in environmental conditions. Certain dinoflagellates forming calcareous cysts, such as Operculodinella operculata, were well adapted to the relatively rapid change of environmental conditions at the K/T boundary, thus blooming to dominate the carbonate flux to the ocean floor. In contrast to the stable Paleocene associations, Eocene calcareous dinoflagellates show fluctuations in relative abundances. These fluctuations can possibly be attributed to redeposition related to increased seaward transport of specimens, due to strengthened western boundary currents. The flora includes two new genera, one new species, and two new forms: Retesphaera diadema Hildebrand-Habel, Willems et Versteegh, gen. et. sp. nov., Cervisiella saxea (Stradner, 1961) Hildebrand-Habel, Willems et Versteegh, gen. et comb. nov., Sphaerodinella? tuberosa forma elongata Hildebrand-Habel, Willems et Versteegh, comb. et forma nov., Sphaerodinella? tuberosa forma variospinosa Hildebrand-Habel, Willems et Versteegh, comb. et forma nov. Three new combinations are proposed: Cervisiella saxea (Stradner, 1961) Hildebrand-Habel, Willems et Versteegh, gen. et comb. nov., Operculodinella operculata (Bramlette et Martini, 1964) Hildebrand-Habel, Willems et Versteegh, comb. nov., and Sphaerodinella? tuberosa (Kamptner, 1963) Hildebrand-Habel, Willems et Versteegh, comb. nov. The genus Operculodinella Kienel, 1994 is emended.

Calcareous dinoflagellates in Maastrichtian to early Miocene sediments of DSDP Hole 39-357

The evolution of calcareous dinoflagellate communities has been investigated for the latest Cretaceous to earliest Neogene interval of the mid-latitude South Atlantic. In doing so, the response of calcareous dinoflagellates to Cenozoic climatic change has been addressed for the first time. Trends in species composition and distribution patterns of wall types indicate significant changes which correlate with major palaeoenvironmental modifications. A first major shift concerning the relative abundance of species and wall types occurred across the Cretaceous-Tertiary boundary. The associations remained stable during the entire Paleocene and Eocene. Only in the late Eocene did a dramatic decrease in temperature cause a slight diversification. A second major shift in the abundance patterns occurred across the Eocene-Oligocene boundary. The early Miocene warming is possibly reflected in the distinct increase in relative abundance of one species. The assemblages of calcareous dinoflagellates evidently react to major climatic changes during the Cenozoic. These poorly investigated organisms may thus provide an important contribution to the understanding of earth's palaeoclimatic evolution.