The dog : a wolf domesticated to communicate with the man

Archeozoology research and molecular genetics have now determined the origin of the canine species and of the first domestication: the wolf is thought to be the main ancestor of dogs, which were domesticated 14 to 15,000 years ago, i.e. 5,000 years before the domestication of another species. There are several hypotheses on the site or sites of this first domestication, all situated on the Eurasian continent. The hypotheses on the reasons for the domestication of dogs and the process by which the species evolved from wolfs are reviewed. The author describes a serie of experiments suggesting that the domestication of dogs leads to a genetic selection improving their understanding of human visual cues and their communication with man.Il est établi, sur la base des recherches en archéozoologie et en génétique moléculaire, que le loup serait le principal ancêtre du chien et que la domestication se serait produite il y a 14000 ou 15000 ans, soit 5000 ans avant la domestication d'une autre espèce. Le ou les lieux de la première domestication font l'objet de discussions et seraient situés sur le continent Eurasiatique. Les hypothèses sur les raisons de la domestication du chien et sur le mécanisme de l'évolution de l'espèce canine à partir du loup sont passées en revue. L'auteur décrit une série d'expériences permettant de supposer que le processus de domestication a conduit à une sélection génétique améliorant la compréhension par le chien des signaux visuels humains et sa communication avec l'homme

Enhancement of Polymeric Immunoglobulin Receptor Transcytosis by Biparatopic VHH

The polymeric immunoglobulin receptor (pIgR) ensures the transport of dimeric immunoglobulin A (dIgA) and pentameric immunoglobulin M (pIgM) across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM) and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers