Range expansion of the greater white-toothed shrew Crocidura russula in Switzerland results in local extinction of the bicoloured white-toothed shrew C-leucodon

The distribution limits of Crocidura russula (Hermann, 1780) and C. leucodon (Hermann, 1780) were investigated during an interval of 25 years in the bottom of the Rhone valley above Lake Geneva, Switzerland (total data set: 105 spatio-temporal occurrences, 1137 shrews). In 1975, the contact zone between the two species was situated in the region of Martigny. In 1999/2000, new sampling revealed three results: (1) The contact zone showed an upward shift of about 25 km. (2) In the expanded range of C. russula, the resident species has totally disappeared (confirmed by owl pellets analysis). (3) This demonstrates a dominance of C, russula over C. leucodon. Three hypotheses which may explain the range expansion of C. russula were evaluated: (1) habitat modification favouring linear dispersal due to the construction of a highway; (2) temporal event favoured by climate fluctuations, or (3) ongoing postglacial colonisation of Europe. Hypothesis 1 was rejected, because the progression of the shrews anticipated the construction. Hypothesis 3 received only weak support because range limits of C. russula in the region of Nice have been stable for thousands of years. Therefore hypothesis 2, admitting that ongoing climate change has facilitated range expansion, is the most probable.

Molecular characterization of Unc5CL/ZUD

Résumé : Au cours de l'évolution, les organismes multicellulaires ont développé le système immunitaire afin de pouvoir se défendre contre les pathogènes tel que les bactéries, les virus, et les parasites. La réponse immunitaire doit être finement régulée par différentes voies de signalisation moléculaire, afin d'assurer une efficacité optimale, et d'éviter des dommages tissulaires indésirables. Les résultats expérimentaux décrits dans ce manuscrit, mettent en évidence que la protéine Unc5CL, qui contient un death domain (DD), est impliquée dans la régulation de la réponse immunitaire des muqueuses. Il a été démontré que cette protéine contient aussi un domaine transmembranaire de type III dans sa partie N-terminale, permettant ainsi de l'ancrer et d'exposer sa partie C-terminale dans le cytosol, un prérequis pour la signalisation dans ce compartiment cellulaire. De plus, cette protéine a la capacité d'activer le facteur de transcription NFxB, qui joue un rôle important dans le système immunitaire, ainsi que dans d'autres processus cellulaires essentiels. Le profil transcriptionnel révèle que l'activation de NF-κB induite par Unc5CL conduit principalement à une réponse inflammatoire, qui se caractérise par la production de diverses chimiokines (e.g. CXCL-1, IL-8 et CCL20). Il a également été démontré que Unc5CL requiert les mêmes molécules qui sont utilisées dans la voie de signalisation des récepteurs de la famille toll et de l'interleukine-1. De manière similaire à leur protéine adaptatrice MyD88, Unc5CL a la capacité de recruter, via une interaction homotypique DD-DD, les kinases IRAK1 et IRAK4 qui contiennent elles aussi un DD, permettant ainsi au signal d'être transmis. La production d'un anticorps polyclonal contre le DD de Unc5CL a permis d'identifier des lignées cellulaires et des tissus exprimant cette protéine, ainsi que de déterminer sa localisation sub-cellulaire. Unc5CL a été détecté dans les cellules de la muqueuse utérine et intestinale, ainsi que dans une lignée cellulaire issue d'un adénocarcinome colorectal humain, les CaCo-2. Dans chacun de ces cas, Unc5CL a été principalement détectée au niveau apical des cellules épithéliales polarisées. De manière similaire à PIDD, une protéine impliquée dans la réponse aux dommages à l'ADN, et au constituant des pores nucléaires Nup98, Unc5CL est constitutivement clivé de manière autoprotéolytique, au niveau d'un site HFS. Il est intéressant d'observer que les deux fragments ainsi générés restent fortement associés l'un à l'autre après clivage. Finalement, un criblage protéomique pour identifier un partenaire d'interaction, a mis en évidence l'ubiquitin ligase E3 ITCH, qui régule de manière négative Unc5CL en augmentant sa dégradation. Summary : Multicellular organisms have evolved the immune system in order to defend themselves against pathogens such as bacteria, viruses and eukaryotic parasites. Immune responses have to be tightly orchestrated by signaling mechanisms to achieve optimal effectiveness and minimal tissue damage. The experimental results in this thesis manuscript provide evidence that the death domain (DD)-containing protein Unc5CL might be involved in the regulation of mucosal immune responses. It could be shown that the protein contains an N-terminal type-III transmembrane domain that anchors the protein with its C-terminus exposed to the cytosol, a prerequisite for signaling events in this compartment. Furthermore, the protein has the capacity to activate the transcription factor NF-κB, which plays an important role in the immune system as well as in other essential cellular processes. Transcriptional profiling revealed that Unc5CL-mediated activation of NF-κB mainly leads to an inflammatory response, characterized by the production of chemokines (e.g. CXCL-l, IL-8 and CCL20). Furthermore, it could be shown that Unc5CL requires the same downstream signaling molecules as the evolutionarily ancient tolUinterleukin-1 receptor family. Similar to their adapter protein MyD88, Unc5CL has the capacity to recruit the DD-containing kinases IRAKI and IRAK4 for signaling and can interact with these proteins via homotypic DD-DD interactions. Generation of polyclonal antibodies raised against the DD of Unc5CL allowed the identification of cell lines and tissues that express the endogenous protein as well as to confine its subcellular localization. Unc5CL was detected in primary mucosal uterine and intestinal epithelial cells as well as in the human colorectal adenocarcinoma cell line CaCo-2. In all cases, the protein was mainly localized to the apical face of these polarized epithelial cells. Similar to PIDD, a protein critically involved in responses to DNA damage, and the nuclear pore component Nup98, Unc5CL is constitutively autoproteolytically processed at an HFS site. Interestingly, the two generated cleavage fragments remain tightly associated after processing. Finally, a proteomics screen for interaction partners identified the E3 ubiquitin ligase ITCH as a negative regulator of Unc5CL by targeting the protein for degradation.

Dysfunction of epithelial sodium transport: from human to mouse.

The highly amiloride-sensitive epithelial sodium channel (ENaC) is an apical membrane constituent of cells of many salt-absorbing epithelia. In the kidney, the functional relevance of ENaC expression has been well established. ENaC mediates the aldosterone-dependent sodium reabsorption in the distal nephron and is involved in the regulation of blood pressure. Mutations in genes encoding ENaC subunits are causative for two human inherited diseases: Liddle's syndrome, a severe form of hypertension associated with ENaC hyperfunction, and pseudohypoaldosteronism (PHA-1), a salt-wasting syndrome caused by decreased ENaC function. Transgenic mouse technologies provide a useful tool to study the role of ENaC in vivo. Different mouse lines have been established in which each of the ENaC subunits was affected. The phenotypes observed in these mice demonstrated that each subunit is essential for survival and for regulation of sodium transport in kidney and colon. Moreover, the alpha subunit plays a specific role in the control of fluid absorption in the airways at birth. Such mice can now be used to study the role of ENaC in various organs and can serve as models to understand the pathophysiology of these human diseases.

Big brother is watching you: eavesdropping to resolve family conflicts

Adult animals can eavesdrop on behavioral interactions between potential opponents to assess their competitive ability and motivation to contest resources without interacting directly with them. Surprisingly, eavesdropping is not yet considered as an important factor used to resolve conflicts between family members. In this study, we show that nestling barn owls (Tyto alba) competing for food eavesdrop on nestmates' vocal interactions to assess the dominance status and food needs of opponents. During a first training playback session, we broadcasted to singleton bystander nestlings a simulated vocal interaction between 2 prerecorded individuals, 1 relatively old (i.e., senior) and 1 younger nestling (i.e., junior). One playback individual, the "responder," called systematically just after the "initiator" playback individual, hence displaying a higher hunger level. To test whether nestlings have eavesdropped on this interaction, we broadcasted the same prerecorded individuals separately in a subsequent playback test session. Nestlings vocalized more rapidly after former initiators' than responders' calls and they produced more calls when the broadcasted individual was formerly a junior initiator. They chiefly challenged vocally juniors and initiators against whom the likelihood of winning a vocal contest is higher. Owlets, therefore, identified the age hierarchy between 2 competitors based on their vocalizations. They also memorized the dynamics of competitors' previous vocal interactions, and used this information to optimally adjust signaling level once interacting with only 1 of the competitor. We conclude that siblings eavesdrop on one another to resolve conflicts over parental resources.