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  1. Article ; Online: Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation.

    Darrau, Estelle / Jacquemet, Elise / Pons, Stéphanie / Schlick, Laurène / Zouridakis, Marios / Wu, Ching-Lien / Richard, Jean-Romain / Barau, Caroline / Le Corvoisier, Philippe / Yolken, Robert / Tamouza, Ryad / Leboyer, Marion / Maskos, Uwe

    Translational psychiatry

    2024  Volume 14, Issue 1, Page(s) 146

    Abstract: There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic ... ...

    Abstract There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic acetylcholine receptor (nAChR) in inflammatory subgroups of psychiatric patients with bipolar disorder (BD) or schizophrenia (SCZ) and healthy controls. We have identified a continuum of AAb levels in serum when employing a novel ELISA technique, with a significant elevation in patients compared to controls. Using unsupervised two-step clustering to stratify all the subjects according to their immuno-inflammatory background, we delineate one subgroup consisting solely of psychiatric patients with severe symptoms, high inflammatory profile, and significantly increased levels of anti-nAChR AAbs. In this context, we have used monoclonal mouse anti-human α7-nAChR antibodies (α7-nAChR-mAbs) and shown that TNF-α release was enhanced upon LPS stimulation in macrophages pre-incubated with α7-nAChR-mAbs compared to the use of an isotype control. These findings provide a basis for further study of circulating nicotinic AAbs, and the inflammatory profile observed in patients with major mood and psychotic disorders.
    MeSH term(s) Humans ; Mice ; Animals ; Bipolar Disorder ; Schizophrenia ; alpha7 Nicotinic Acetylcholine Receptor ; Inflammation/metabolism ; Receptors, Nicotinic ; Autoantibodies
    Chemical Substances alpha7 Nicotinic Acetylcholine Receptor ; Receptors, Nicotinic ; Autoantibodies
    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2609311-X
    ISSN 2158-3188 ; 2158-3188
    ISSN (online) 2158-3188
    ISSN 2158-3188
    DOI 10.1038/s41398-024-02853-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A conserved NR5A1-responsive enhancer regulates SRY in testis-determination.

    Houzelstein, Denis / Eozenou, Caroline / Lagos, Carlos F / Elzaiat, Maëva / Bignon-Topalovic, Joelle / Gonzalez, Inma / Laville, Vincent / Schlick, Laurène / Wankanit, Somboon / Madon, Prochi / Kirtane, Jyotsna / Athalye, Arundhati / Buonocore, Federica / Bigou, Stéphanie / Conway, Gerard S / Bohl, Delphine / Achermann, John C / Bashamboo, Anu / McElreavey, Ken

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2796

    Abstract: The Y-linked SRY gene initiates mammalian testis-determination. However, how the expression of SRY is regulated remains elusive. Here, we demonstrate that a conserved steroidogenic factor-1 (SF-1)/NR5A1 binding enhancer is required for appropriate SRY ... ...

    Abstract The Y-linked SRY gene initiates mammalian testis-determination. However, how the expression of SRY is regulated remains elusive. Here, we demonstrate that a conserved steroidogenic factor-1 (SF-1)/NR5A1 binding enhancer is required for appropriate SRY expression to initiate testis-determination in humans. Comparative sequence analysis of SRY 5' regions in mammals identified an evolutionary conserved SF-1/NR5A1-binding motif within a 250 bp region of open chromatin located 5 kilobases upstream of the SRY transcription start site. Genomic analysis of 46,XY individuals with disrupted testis-determination, including a large multigenerational family, identified unique single-base substitutions of highly conserved residues within the SF-1/NR5A1-binding element. In silico modelling and in vitro assays demonstrate the enhancer properties of the NR5A1 motif. Deletion of this hemizygous element by genome-editing, in a novel in vitro cellular model recapitulating human Sertoli cell formation, resulted in a significant reduction in expression of SRY. Therefore, human NR5A1 acts as a regulatory switch between testis and ovary development by upregulating SRY expression, a role that may predate the eutherian radiation. We show that disruption of an enhancer can phenocopy variants in the coding regions of SRY that cause human testis dysgenesis. Since disease causing variants in enhancers are currently rare, the regulation of gene expression in testis-determination offers a paradigm to define enhancer activity in a key developmental process.
    MeSH term(s) Animals ; Female ; Humans ; Male ; Cell Line ; Gonadal Dysgenesis ; Mammals/genetics ; Regulatory Sequences, Nucleic Acid ; Sertoli Cells/metabolism ; Sex-Determining Region Y Protein/genetics ; Steroidogenic Factor 1/genetics ; Steroidogenic Factor 1/metabolism ; Testis/metabolism
    Chemical Substances NR5A1 protein, human ; Sex-Determining Region Y Protein ; Steroidogenic Factor 1 ; SRY protein, human ; HTRA2 protein, human (EC 3.4.21.108)
    Language English
    Publishing date 2024-03-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47162-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Functional maturation of human iPSC-derived pyramidal neurons

    Raïs, Célia / Gaspar Santos, Daniela / Sansone, Giulia / Blanchard, Stéphane / Bourgeois, Jean-Pierre / Jagla, Bernd / Saudemont, Baptiste / Schlick, Laurène / Pons, Stéphanie / Maskos, Uwe

    Frontiers in cellular neuroscience

    2023  Volume 17, Page(s) 1259712

    Abstract: Human induced pluripotent stem cells (hiPSCs) have been used ... ...

    Abstract Human induced pluripotent stem cells (hiPSCs) have been used extensively
    Language English
    Publishing date 2023-11-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2023.1259712
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations.

    Hervé, Virginie / Rabbe, Nathalie / Guilleminault, Laurent / Paul, Flora / Schlick, Laurène / Azzopardi, Nicolas / Duruisseaux, Michael / Fouquenet, Delphine / Montharu, Jérôme / Redini, Françoise / Paintaud, Gilles / Lemarié, Etienne / Cadranel, Jacques / Wislez, Marie / Heuzé-Vourc'h, Nathalie

    mAbs

    2014  Volume 6, Issue 6, Page(s) 1638–1648

    Abstract: K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target ... ...

    Abstract K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras(LA1) model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations.
    MeSH term(s) Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Aerosols ; Animals ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/pharmacology ; Antibodies, Neutralizing/administration & dosage ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/pharmacology ; Area Under Curve ; Biological Availability ; Blotting, Western ; Cell Proliferation/drug effects ; Cells, Cultured ; Humans ; Immunohistochemistry ; Injections, Intraperitoneal ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/prevention & control ; Proto-Oncogene Proteins p21(ras)/genetics ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/immunology ; Vascular Endothelial Growth Factor Receptor-2/metabolism
    Chemical Substances Aerosols ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Vascular Endothelial Growth Factor A ; Kdr protein, mouse (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; Kras2 protein, mouse (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2014
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1942-0870
    ISSN (online) 1942-0870
    DOI 10.4161/mabs.34454
    Database MEDical Literature Analysis and Retrieval System OnLINE

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