1. Preventing Dangerous Climate Change or Turning It into a Huge Economic Opportunity for big business?Judged against low expectations and the collective trauma of Copenhagen 2009, the acceptance of the global and leg...
1. Preventing Dangerous Climate Change or Turning It into a Huge Economic Opportunity for big business?Judged against low expectations and the collective trauma of Copenhagen 2009, the acceptance of the global and legally binding Paris Agreement on Saturday, 12th of December,at 19:26, is a historical moment. It achieves a goal long believed unattainable on the long road from bali(2007) via Durban(2011).
The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis ...
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The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.
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