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Abstract Background Based on sequence similarity, the superfamily of G protein-coupled receptors (GPRs) can be subdivided into several subfamilies, the members of which often share similar ligands. The sequence data provided by the human genome project allows us to identify new GPRs by in silico homology screening, and to predict their ligands. Results By searching the human genomic database with known nucleotide receptors we discovered the gene for GPR99, a new orphan GPR. The mRNA of GPR99 was found in kidney and placenta. Phylogenetic analysis groups GPR99 into the P2Y subfamily of GPRs. Based on the phylogenetic tree we propose a new classification of P2Y nucleotide receptors into two subgroups predicting a nucleotide ligand for GPR99. By assaying known nucleotide ligands on heterologously expressed GPR99, we could not identify specifically activating substances, indicating that either they are not agonists of GPR99 or that GPR99 was not expressed at the cell surface. Analysis of the chromosomal localization of all genes of the P2Y subfamily revealed that all members of subgroup "a" are encoded by less than 370 kb on chromosome 3q24, and that the genes of subgroup "b" are clustered on one hand to chromosome 11q13.5 and on the other on chromosome 3q24-25.1 close to the subgroup "a" position. Therefore, the P2Y subfamily is a striking example for local gene amplification. Conclusions We identified a new orphan receptor, GPR99, with homology to the family of G protein-coupled nucleotide receptors. Phylogenetic analysis separates this family into different subgroups predicting a nucleotide ligand for GPR99.

The German Constitutional Court is currently reviewing whether the actual study admission process in medicine is compatible with the constitutional right of freedom of profession, since applicants without an excellent GPA usually have to wait for seven years. If the admission system is changed, politicians would like to increase the influence of psychosocial criteria on selection as specified by the Masterplan Medizinstudium 2020.What experiences have been made with the actual selection procedures? How could Situational Judgement Tests contribute to the validity of future selection procedures to German medical schools?High school GPA is the best predictor of study performance, but is more and more under discussion due to the lack of comparability between states and schools and the growing number of applicants with top grades. Aptitude and knowledge tests, especially in the natural sciences, show incremental validity in predicting study performance. The measurement of psychosocial competencies with traditional interviews shows rather low reliability and validity. The more reliable multiple mini-interviews are superior in predicting practical study performance. Situational judgement tests (SJTs) used abroad are regarded as reliable and valid; the correlation of a German SJT piloted in Hamburg with the multiple mini-interview is cautiously encouraging.A model proposed by the Medizinischer Fakultätentag and the Bundesvertretung der Medizinstudierenden considers these results. Student selection is proposed to be based on a combination of high school GPA (40%) and a cognitive test (40%) as well as an SJT (10%) and job experience (10%). Furthermore, the faculties still have the option to carry out specific selection procedures.

The single transmembrane receptor sorLA/LR11 contains binding domains typical for the low-density lipoprotein receptors and a VPS10 domain which, in the related receptor sortilin, binds the neuropeptide neurotensin. SorLA is synthesized as a proreceptor which is processed to the mature form by a furin-like propeptidase. Endogenous sorLA and its hydra homologue HAB bind the neuropeptide head activator (HA). Transiently expressed partial sorLA constructs were investigated for ligand binding. We found that HA binds with nanomolar affinity to the VPS10 domain. The sorLA propeptide also bound to the VPS10 domain, whereas the receptor-associated protein RAP interacted both with the class A repeats and the VPS10 domain. The sorLA propeptide inhibited binding of HA to full-length sorLA and to the VPS10 domain. It also interfered with binding of HA to hydra HAB, which is taken as evidence for a highly conserved tertiary structure of the VPS10 domains of this receptor in hydra and mammals. The propeptide inhibited HA-stimulated mitosis and proliferation in the human neuroendocrine cell line BON and the neuronal precursor cell line NT2. We conclude that sorLA is necessary for HA signaling and function.