Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

A post-transplant person:narratives of heart or lung transplantation and intensive care unit delirium

Exploring patients' narratives can lead to new understandings about perceived illness states. Intensive Care Unit delirium is when people experience transitory hallucinations, delusions or paranoia in the Intensive Care Unit and little is known about how this experience affects individuals who have had a heart or lung transplant. A total of 11 participants were recruited from two heart and lung transplant services and were invited to tell their story of transplant and Intensive Care Unit delirium. A narrative analysis was conducted and the findings were presented as a shared story. This shared story begins with death becoming prominent before the transplant: 'you live all the time with Mr Death on your shoulder'. Following the operation, death permeates all aspects of dream worlds, as dreams in intensive care 'tunes into the subconscious of your fears'. The next part of the shared story offers hope of restitution; however, this does not last as reality creeps in: 'I thought it was going to be like a miracle cure'. Finally, the restitution narrative is found to be insufficient and individuals differ in the extent to which they can achieve resolution. The societal discourse of a transplant being a 'gift', which gives life, leads to internalised responsibility for the 'success' or 'failure' of the transplant. Participants describe how their experiences impact their sense of self: 'a post-transplant person'. The clinical implications of these findings are discussed

AN OPTIMIZATION PROBLEM FOR A PRODUCTION SYSTEM WITH REAL OPTION APPROACH (Nonlinear Analysis and Convex Analysis)

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes