Here we report that the NAD1-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase,

which opposes the acetylation-induced HER2 inhibitor NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density this website as a consequence of enhanced

Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.”
“The script concordance test (SCT) is used in health professions education to assess a specific facet of clinical reasoning competence: the ability to interpret medical information under conditions of uncertainty. Grounded in established theoretical models of knowledge organization and clinical reasoning, the SCT has three key design features: (1) respondents are faced with ill-defined clinical situations and must choose between several realistic options; (2)

the response format reflects the way information is processed in challenging problem-solving situations; and (3) scoring takes into account the variability of responses of experts to clinical situations. SCT scores are meant to reflect how closely respondents’ ability to interpret clinical data compares with that of experienced clinicians in a given knowledge domain. A substantial PU-H71 chemical structure body of research supports the SCT’s construct validity, reliability, and feasibility across a variety of health science disciplines, and across the spectrum of health professions education from pre-clinical training to continuing professional development. In practice, its performance as an assessment tool depends on careful item development and diligent panel selection. This guide, intended as a primer for the uninitiated in SCT, will cover the basic tenets, theoretical underpinnings, and construction principles governing script concordance testing.”
“A thin liquid crystal (LC) lens of 2.0 mm aperture diameter and less than 1 mm thickness is realized by placing a highly resistive film in an LC cell. Two LC layers of 30 mu m thickness are used to achieve a lens power ranging from approximately -6.5 to 6.7 m(-1). The cell is driven by two voltages under 40 V-rms.