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10.4049/jimmunol.1400326 http://scihub22266oqcxt.onion/10.4049/jimmunol.1400326 C4355390!4355390 !25662996     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25662996 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Immunol 2015 ; 194 (6 ): 2587-95 Nephropedia Template TP {{tp|p=25662996 |t=2015. Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation |pdf=|usr=}}{{25662996 }} gab.com Text Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation JO: J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=25662996 #FOAvip Gene variants that disrupt TCR signaling can cause severe immune deficiency, yet less disruptive variants are sometimes associated with immune pathology. Null mutations of the gene encoding the scaffold protein Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76), for example, cause an arrest of T cell positive selection, whereas a synthetic membrane-targeted allele allows limited positive selection but is associated with proinflammatory cytokine production and autoantibodies. Whether these and other enigmatic outcomes are due to a biochemical uncoupling of tolerogenic signaling, or simply a quantitative reduction of protein activity, remains to be determined. In this study we describe a splice variant of Lcp2 that reduced the amount of wild-type SLP-76 protein by ~90%, disrupting immunogenic and tolerogenic pathways to different degrees. Mutant mice produced excessive amounts of proinflammatory cytokines, autoantibodies, and IgE, revealing that simple quantitative reductions of SLP-76 were sufficient to trigger immune dysregulation. This allele reveals a dose-sensitive threshold for SLP-76 in the balance of immunity and immune dysregulation, a common disturbance of atypical clinical immune deficiencies. Twit Text FOAVip Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation ????J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=25662996 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25662996 #FOAvip English Wikipedia <ref>{{Cite pmid|25662996 }}</ref> Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation #MMPMID25662996 Siggs OM ; Miosge LA ; Daley SR ; Asquith K ; Foster PS ; Liston A ; Goodnow CC J Immunol 2015[Mar]; 194 (6 ): 2587-95 PMID25662996 show ga Gene variants that disrupt TCR signaling can cause severe immune deficiency, yet less disruptive variants are sometimes associated with immune pathology. Null mutations of the gene encoding the scaffold protein Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76), for example, cause an arrest of T cell positive selection, whereas a synthetic membrane-targeted allele allows limited positive selection but is associated with proinflammatory cytokine production and autoantibodies. Whether these and other enigmatic outcomes are due to a biochemical uncoupling of tolerogenic signaling, or simply a quantitative reduction of protein activity, remains to be determined. In this study we describe a splice variant of Lcp2 that reduced the amount of wild-type SLP-76 protein by ~90%, disrupting immunogenic and tolerogenic pathways to different degrees. Mutant mice produced excessive amounts of proinflammatory cytokines, autoantibodies, and IgE, revealing that simple quantitative reductions of SLP-76 were sufficient to trigger immune dysregulation. This allele reveals a dose-sensitive threshold for SLP-76 in the balance of immunity and immune dysregulation, a common disturbance of atypical clinical immune deficiencies. |Adaptor Proteins, Signal Transducing/genetics/*immunology/metabolism [MESH] |Animals [MESH] |Antibodies, Antinuclear/immunology/metabolism [MESH] |Blotting, Western [MESH] |Cytokines/immunology/metabolism [MESH] |Female [MESH] |Flow Cytometry [MESH] |Immunity/genetics/*immunology [MESH] |Immunoglobulin E/immunology/metabolism [MESH] |Immunoglobulin G/immunology/metabolism [MESH] |Inflammation Mediators/immunology/metabolism [MESH] |Male [MESH] |Mice, Inbred C57BL [MESH] |Mice, Mutant Strains [MESH] |Mice, Transgenic [MESH] |Mutation/immunology [MESH] |Phosphoproteins/genetics/*immunology/metabolism [MESH] |Signal Transduction/genetics/*immunology [MESH] |T-Lymphocytes/immunology/metabolism [MESH]Quantitative reduction of the TCR adapter protein SLP-76 unbalances im(epmc).pdf DeepDyve Pubget Overpricing