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Polycystin-1 is a large transmembrane protein, which, when mutated, causes autosomal dominant polycystic kidney disease, one of the most common life-threatening genetic diseases that is a leading cause of kidney failure. The REJ (receptor for egg lelly) module is a major component of PC1 ectodomain that extends to about 1000 amino acids. Many missense disease-causing mutations map to this module; however, very little is known about the structure or function of this region. We used a combination of homology molecular modeling, protein engineering, steered molecular dynamics (SMD) simulations, and single-molecule force spectroscopy (SMFS) to analyze the conformation and mechanical stability of the first ~420 amino acids of REJ. Homology molecular modeling analysis revealed that this region may contain structural elements that have an FNIII-like structure, which we named REJd1, REJd2, REJd3, and REJd4.We found that REJd1 has a higher mechanical stability than REJd2 (~190 pN and 60 pN, resp.). Our data suggest that the putative domains REJd3 and REJd4 likely do not form mechanically stable folds. Our experimental approach opens a new way to systematically study the effects of disease-causing mutations on the structure and mechanical properties of the REJ module of PC1. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the reliability of ECG precordial electrode placement by doctors and nurses involved in the emergency care of patients admitted with suspected cardiac diseases. A total of 120 subjects were recruited within 2 days from six hospitals. They comprised physicians, nurses and cardiac technicians involved in the clinical assessment and care of patients with suspected cardiac disease. Subjects were asked to complete a questionnaire and marked on two diagrams of the chest wall the positions they would place precordial electrodes V1-V6. This study showed wide inter-individual and inter-group variations in the placement of electrodes. Notably, V1 and V2 were frequently incorrectly positioned in the second intercostal space, especially by physicians. The correct position of V1 in the fourth right intercostal space was identified by 90% of cardiac technicians, 49% of nurses, 31% of physicians (excluding cardiologists) and - most disappointing of all - only 16% of cardiologists (p < 0.001 for inter-group differences). V5 and V6 were also often mispositioned, too high on the lateral chest wall. Nurses and doctors (especially cardiologists) do not know the correct positions for ECG electrodes. Because incorrect positioning of the precordial electrodes changes the ECG significantly, patients are at risk of potentially harmful therapeutic procedures. Equally, doctors who are aware of the possibility of lead misplacement may be inclined to ignore some ECG changes that may be genuine evidence of ischaemia. The only safe solution is proper precordial electrode placement, which requires training and an environment supporting precision. [ABSTRACT FROM AUTHOR]