http://www.bioinformatics.sussex.ac.uk/protorp

EzMol is a molecular visualization Web server in the form of a software wizard, located at http://www.sbg.bio.ic.ac.uk/ezmol/. It is designed for easy and rapid image manipulation and display of protein molecules, and is intended for users who need to quickly produce high-resolution images of protein molecules but do not have the time or inclination to use a software molecular visualization system. EzMol allows the upload of molecular structure files in PDB format to generate a Web page including a representation of the structure that the user can manipulate. EzMol provides intuitive options for chain display, adjusting the color/transparency of residues, side chains and protein surfaces, and for adding labels to residues. The final adjusted protein image can then be downloaded as a high-resolution image. There are a range of applications for rapid protein display, including the illustration of specific areas of a protein structure and the rapid prototyping of images.

A total of 245 patients undergoing MIPN were included in the study. The presence of APF was determined through keywords in operating notes, and radiographic data were obtained from preoperative cross-sectional imaging. Posterior fat thickness was measured between the renal capsule and the posterior abdominal wall at the level of the renal vein. Perinephric stranding was graded on a 0-3 severity scale. ResultsThe study included 123 men and 122 women, with a median age of 55 years, body mass index of 31.7, tumour size of 2.7 cm and nephrometry score of 6. The median posterior fat thickness was 1.79 cm and MAP score 2.63. In all, 26 patients (10.6%) had evidence of APF at the time of renal surgery. Factors predictive of APF included increasing age (P = 0.001), male gender (P = 0.045), perinephric stranding (P = 0.002), posterior fat thickness (P < 0.001) and MAP score (P < 0.001). APF was associated with adverse pathological and peri-operative outcomes including malignant renal histology (P = 0.04), longer operating time (P = 0.005) and greater estimated blood loss (EBL; P = 0.025). ConclusionsSpecific clinical and radiographic factors predict APF at MIPN. The presence of APF is associated with adverse perioperative outcomes including longer operating time and greater EBL. APF was also associated with renal malignancy on final pathology, but further studies are necessary to elucidate the precise underlying mechanism.

Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity. Importantly, we report a cocrystal structure of one of our compounds (29c) bound to SIRT2. This reveals our series to induce the formation of a previously reported selectivity pocket but to bind in an inverted fashion to what might be intuitively expected. We believe these findings will contribute significantly to an understanding of the mechanism of action of SIRT2 inhibitors and to the identification of refined, second generation inhibitors.