Abstract: The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor ?, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.

Abstract: The present invention relates to a new process for identifying novel anti-inflammatory molecules with reduced direct transrepression of genes induced by glucocorticoids. The inventors have discovered that GCs-mediated transrepression can be mediated not only via the tethering indirect pathway, but also through direct binding of GR to “simple” negative GREs (nGRE), which belongs to a novel family of evolutionary-conserved cis-acting negative response elements (IR nGREs), and are found in numerous GC-repressed genes.

Abstract: A disposable electrode array 100, 200 including a flexible member 106, 206 in which a plurality of electrodes 102, 202 are disposed, having a shape adapted to contact the forehead skin surface on a human patient. A pair of ear loops 104, 204 coupled to the disposable electrode array 100, 200 secure the disposable electrode array 100, 200 about the patient's ears, with the flexible member 106, 206 disposed across the patient's bow, retaining the electrodes 102, 202 against the skin surface. Additional electrodes 102, 202 are disposed in proximity to the ear loops 104, 204 and are configured to contact the skin surface behind the patient's ears. An auditory stimulus delivery element 116, 216 is coupled with each of the ear loops 104, 204, and positioned to seat in proximity to the patient's ear canal for the delivery of auditory stimulus.

Abstract: The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor ?, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.

Abstract: The present invention concerns a method for generating a human atopic disease-like phenotype, preferably an atopic dermatitis (AD)-like phenotype in a mammal comprising administering to said mammal at least one compound selected in the group comprising the physiologically active vitamin D3 (1?,25(OH)2D3) and agonistic analogs thereof. The present invention also concerns a method for treating and/or preventing an atopic disease in a patient in a patent comprising administrating to said patient an effective amount of at least one vitamin D3 antagonist.

Abstract: A disposable electrode array 100, 200 including a flexible member 106, 206 in which a plurality of electrodes 102, 202 are disposed, having a shape adapted to contact the forehead skin surface on a human patient. A pair of ear loops 104, 204 coupled to the disposable electrode array 100, 200 secure the disposable electrode array 100, 200 about the patient's ears, with the flexible member 106, 206 disposed across the patient's bow, retaining the electrodes 102, 202 against the skin surface. Additional electrodes 102, 202 are disposed in proximity to the ear loops 104, 204 and are configured to contact the skin surface behind the patient's ears. An auditory stimulus delivery element 116, 216 is coupled with each of the ear loops 104, 204, and positioned to seat in proximity to the patient's ear canal for the delivery of auditory stimulus.

Abstract: The present invention relates to a metazoan organism, with the exception of humans, and in particular a mouse, characterized in that at least one cell of this organism comprises at least one fusion protein between a recombinase Cre and a modified ligand binding domain of the nuclear estrogen receptor alpha, allowing the inactive fused recombinase to be induced by synthetic antiestrogens, but not by natural estrogens, and one or more DNA sequences of interest belonging to the genome of said organism into which one or more sites of recognition of said recombinase protein are inserted. The invention also covers the methods using said organism for the screening of medicaments, the mutagenesis and the analysis of the biological function of the DNA sequences) of interest, in particular of gene(s) of interest, such as RXR?.

Abstract: A promoter-free nucleic acid construct, includes a selection sequence and a sequence coding for a protein of interest distinct from the selection sequence, the coding sequence being preceded upstream by a sequence enabling its translation by ribosomes and the uses of the construct in the fields of biology and medicine.

Abstract: A DNA fragment coding for a modified nuclear glucocorticoid receptor, particularly one mutated in the region coding for the ligand binding domain, so that receptor activity is more strongly inducible by a synthetic glucocorticoid ligand than by a natural glucocorticoid ligand, is disclosed. A recombination system inducible in mammals by means of a fusion protein produced between a recombinase and the binding domain of the ligand derived from the modified glucocorticoid receptor of which the activity is more strongly inducible by synthetic glucocorticoids than by natural glucocorticoids, is also disclosed.

Abstract: The invention relates to methods for treatment of neurological disease by administering an agent which interacts with a retinoid receptor associated with the neurological disease. The invention is also related to a method of modulating dopamine receptor synthesis by introducing an agent that interacts with a retinoid receptor associated with the dopamine receptor synthesis. The invention is further related to a transgenic animal, e.g., mouse, and mammalian cell line, which is deficient in the normal synthesis of one or more receptors of RAR&agr;, &bgr;, &ggr; and RXR, and cell line thereof.

Abstract: The present invention relates to a method for the preparation of a protein by yeasts. In particular, the method of the invention concerns transforming a yeast cell with a first DNA fragment encoding the protein and a second DNA fragment that encodes the receptor. The method further entails culturing the transformed yeast cell, and isolating the protein. The first DNA fragment is under control of elements providing for expression of the DNA fragment in yeast, which elements include a higher eukaryotic positive transcription control sequence consisting of a natural ligand responsive element activating sequence or a variant. The receptor is a natural nuclear receptor selected from the group consisting of receptors for steroids or for retinoids or for thyroid hormones or for vitamin D3. The receptor includes a first fragment that recognizes said ligand and a second fragment that binds to said transcriptional control sequence.

Abstract: The present invention relates to a metazoan organism, with the exception of humans, and in particular a mouse, characterized in that at least one cell of this organism comprises at least one fusion protein between a recombinase Cre and a modified ligand binding domain of the nuclear estrogen receptor alpha, allowing the inactive fused recombinase to be induced by synthetic antiestrogens, but not by natural estrogens, and one or more DNA sequences of interest belonging to the genome of said organism into which one or more sites of recognition of said recombinase protein are inserted. The invention also covers the methods using said organism for the screening of medicaments, the mutagenesis and the analysis of the biological function of the DNA sequences) of interest, in particular of gene(s) of interest, such as RXR&agr;.

Abstract: The present invention relates to a method for the preparation of a protein by yeasts, according to which:yeast cells which contain the following are cultured:a DNA sequence coding for the protein under the control of elements providing for its expression in yeasts, the elements comprising a transcription control sequence which is inducible by a complex formed by a receptor and a ligand,a DNA sequence which is functional in yeast, coding for the receptor, the receptor comprising two essential portions, one of which recognizes the ligand so as to form a complex with the ligand and the other binds to the said transcription control sequence; the portion of the receptor which recognizes the ligand is of higher eukaryotic origin, and the ligand is not necessary for the culturing of the cells but is capable of entering the cells when added to the culture medium,the ligand is added to the culture medium at an appropriate time point for induction,the synthesized protein is recovered.