The infevers autoinflammatory mutation online registry: update with new genes and functions.

Infevers (Internet Fevers; http://fmf.igh.cnrs.fr/ISSAID/infevers), a website dedicated to mutations responsible for hereditary autoinflammatory diseases, was created in 2002 and has continued to evolve. This new version includes eight genes; six were already present: MEFV, MVK, TNFRSF1A, NLRP3, NOD2, PSTPIP1, and two are new, LPIN2 and NLRP7. Currently, Infevers contains over 540 sequence variants. Several new database functions were recently instituted. The website now accepts confidential data and complex alleles. For each gene, a newly created menu offers: 1) a tabular list of the variants that can be sorted by several parameters; 2) a gene graph providing a schematic representation of the variants along the gene; 3) statistical analysis of the data according to the phenotype, alteration type, and location of the mutation in the gene; 4) the cDNA and gDNA sequences of each gene, showing the nucleotide changes along the sequence, with a color-based code highlighting the gene domains, the first ATG, and the termination codon; and 5) a "download" menu making all tables and figures available for the users, which, except for the gene graphs, are all automatically generated and updated upon submission of the variants. Finally, the entire database was curated to comply with the HUGO Gene Nomenclature Committee (HGNC) and HGVS nomenclature guidelines, and wherever necessary, an informative note was provided. Infevers has already proven useful for the scientific community with a mean number of visits per month of 200 in 2002 and 800 in 2007, and its new design will lead to a more comprehensive comparative analysis and interpretation of auto-inflammatory sequence variants.

Infevers: an evolving mutation database for auto-inflammatory syndromes.

The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.

Structural requirements of the N-terminal region of GLP-1-[7-37]-NH2 for receptor interaction and cAMP production.

A series of GLP-1-[7-36]-NH(2) (tGLP-1) and GLP-1-[7-37] analogs modified in position 7, 8, 9 and 36, have been designed and evaluated on murine GLP-1 receptors expressed in RIN T3 cells for both their affinity and activity. Ten of the synthesized peptides were found full agonists with activities superior or at least equal to that of the native hormone. Five of them were investigated for their plasmatic stability and the most stable, [a(8)-desR(36)]GLP-1-[7-37]- NH(2) (Compound 8), evaluated in vivo in a glucose tolerance test which confirmed a clearly longer activity than that of the native hormone. We also performed circular dichroism study and propose a hypothetical structural model explaining the most part of observed activities of GLP-1 analogs on RIN T3 cells.

INFEVERS: the Registry for FMF and hereditary inflammatory disorders mutations.

We have established the INFEVERS--INternet periodic FEVERS--website (which is freely accessible at http://fmf.igh.cnrs.fr/infevers/). Our objectives were to develop a specialist site to gather updated information on mutations responsible for hereditary inflammatory disorders: i.e. Familial Mediterranean Fever (FMF), TRAPS (TNF Receptor 1A Associated Syndrome), HIDS (HyperIgD Syndrome), MWS (Muckle-Wells Syndrome)/FCU (Familial Cold Urticaria)/CINCA (Chronic Infantile Neurological Cutaneous and Articular Syndrome). Contributors submit their novel mutations through a 3 step form. Depending on the disease concerned, a member of the editorial board is automatically solicited to overview and validate new submissions, via a special secured web interface. If accepted, the new mutation is available on the INFEVERS web site and the discoverer, who is informed by email, is credited by having his/her name and date of the discovery on the site. The INFEVERS gateway provides researchers and clinicians with a common access location for information on similar diseases, allowing a rapid overview of the corresponding genetic defects at a glance. Furthermore, it is interactive and extendable according to the latest genes discovered.

The MetaFMF website: a high quality tool for meta-analysis of FMF.

We present here the MetaFMF database (freely accessible at http://fmf.igh.cnrs.fr/metaFMF/index_us.html) that attempts to gather and unify, in a common resource, data on phenotype-genotype correlation in familial Mediterranean fever (FMF). A single accession form, including a large number of quality controls, has been implemented such that data, collected worldwide, are included in an homogeneous manner. The inclusion criterion has the objective to avoid interpretational bias: patients will be included only if they bear at least two mutations. The clinical form has been set up by an International editorial board (12 FMF expert centres), which guarantees the validity of the data. Data are anonymous and submitted by a secure interface, in which the researcher is logged in with a specific ID and password. A pilot study on 211 patients has shown the feasibility and relevance of this project. We anticipate that the use of MetaFMF will enable reliable assessment of phenotype-genotype correlations in FMF, and define a set of severe versus mild mutations/genotypes. It should also highlight reasons for previous inconsistencies in such correlations.

The Ume6 regulon coordinates metabolic and meiotic gene expression in yeast.

The Ume6 transcription factor in yeast is known to both repress and activate expression of diverse genes during growth and meiotic development. To obtain a more complete profile of the functions regulated by this protein, microarray analysis was used to examine transcription in wild-type and ume6Delta diploids during vegetative growth in glucose and acetate. Two different genetic backgrounds (W303 and SK1) were examined to identify a core set of strain-independent Ume6-regulated genes. Among genes whose expression is controlled by Ume6 in both backgrounds, 82 contain homologies to the Ume6-binding site (URS1) and are expected to be directly regulated by Ume6. The vast majority of those whose functions are known participate in carbon/nitrogen metabolism and/or meiosis. Approximately half of the Ume6 direct targets are induced during meiosis, with most falling into the early meiotic expression class (cluster 4), and a smaller subset in the middle and later classes (clusters 5-7). Based on these data, we propose that Ume6 serves a unique role in diploid cells, coupling metabolic responses to nutritional cues with the initiation and progression of meiosis. Finally, expression patterns in the two genetic backgrounds suggest that SK1 is better adapted to respiration and W303 to fermentation, which may in part account for the more efficient and synchronous sporulation of SK1.