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10.15252/emmm.201708483 http://scihub22266oqcxt.onion/10.15252/emmm.201708483 C5887907!5887907 !29567797     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29567797 &cmd=llinks): Failed to open stream: HTTP request failed! 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Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis |pdf=|usr=}}{{29567797 }} gab.com Text Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis JO: EMBO Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=29567797 #FOAvip Herein, we report the first identification of biallelic-inherited mutations in ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated patients. ALPI encodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll-like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter-subunit interactions, and heterologous expression in HEK293T cells demonstrated that all ALPI mutations were loss of function. ALPI mutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide-dependent signalling. Furthermore, ALPI expression was reduced in patients' biopsies, and ALPI activity was undetectable in ALPI-deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host-microbiota interactions and restraining host inflammatory responses. These results indicate that ALPI mutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI-based treatments in intestinal inflammatory disorders. Twit Text FOAVip Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis ????EMBO Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=29567797 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29567797 #FOAvip English Wikipedia <ref>{{Cite pmid|29567797 }}</ref> Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis #MMPMID29567797 Parlato M ; Charbit-Henrion F ; Pan J ; Romano C ; Duclaux-Loras R ; Le Du MH ; Warner N ; Francalanci P ; Bruneau J ; Bras M ; Zarhrate M ; Bègue B ; Guegan N ; Rakotobe S ; Kapel N ; De Angelis P ; Griffiths AM ; Fiedler K ; Crowley E ; Ruemmele F ; Muise AM ; Cerf-Bensussan N EMBO Mol Med 2018[Apr]; 10 (4 ): ä PMID29567797 show ga Herein, we report the first identification of biallelic-inherited mutations in ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated patients. ALPI encodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll-like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter-subunit interactions, and heterologous expression in HEK293T cells demonstrated that all ALPI mutations were loss of function. ALPI mutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide-dependent signalling. Furthermore, ALPI expression was reduced in patients' biopsies, and ALPI activity was undetectable in ALPI-deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host-microbiota interactions and restraining host inflammatory responses. These results indicate that ALPI mutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI-based treatments in intestinal inflammatory disorders. |Alkaline Phosphatase/deficiency/genetics/*metabolism [MESH] |GPI-Linked Proteins/deficiency/genetics/metabolism [MESH] |HEK293 Cells [MESH] |Homeostasis [MESH] |Humans [MESH] |Inflammatory Bowel Diseases/genetics/*metabolism [MESH] |Intestines [MESH] |Mutation/genetics [MESH]Human ALPI deficiency causes inflammatory bowel disease and highlights(epmc).pdf DeepDyve Pubget Overpricing