Reactive oxygen-derived free radicals are key to the endothelial dysfunction of diabetes.

Vascular complications are an important pathological issue in diabetes that lead to the further functional deterioration of several organs. The balance between endothelium-dependent relaxing factors and endothelium-dependent contracting factors (EDCFs) is crucial in controlling local vascular tone and function under normal conditions. Diabetic endothelial dysfunction is characterized by reduced endothelium-dependent relaxations and/or enhanced endothelium-dependent contractions. Elevated levels of oxygen-derived free radicals are the initial source of endothelial dysfunction in diabetes. Oxygen-derived free radicals not only reduce nitric oxide bioavailability, but also facilitate the production and/or action of EDCFs. Thus, the endothelial balance tips towards vasoconstrictor responses over the course of diabetes. © 2009 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.postprin

Community-developed checklists for publishing images and image analysis

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However for scientists wishing to publish the obtained images and image analyses results, there are to date no unified guidelines. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here we present community-developed checklists for preparing light microscopy images and image analysis for publications. These checklists offer authors, readers, and publishers key recommendations for image formatting and annotation, color selection, data availability, and for reporting image analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby heighten the quality of microscopy data is in publications.Comment: 28 pages, 8 Figures, 3 Supplmentary Figures, Manuscript, Essential recommendations for publication of microscopy image dat

Signalling complexes and clusters: functional advantages and methodological hurdles.

International audienceSignalling molecules integrate, codify and transport information in cells. Organisation of these molecules in complexes and clusters improves the efficiency, fidelity and robustness of cellular signalling. Here, we summarise current views on how signalling molecules assemble into macromolecular complexes and clusters and how they use their physical properties to transduce environmental information into a variety of cellular processes. In addition, we discuss recent innovations in live-cell imaging at the sub-micrometer scale and the challenges of object (particle) tracking, both of which help us to observe signalling complexes and clusters and to examine their dynamic character

Volar fixed-angle plating of distal radius extension fractures: influence of plate position on secondary loss of reduction: a biomechanic study in a cadaveric model

Purpose: Treatment of extension fractures of the distal radius with volar fixed-angle plates has become increasingly popular in the past 2 years. It has been observed clinically that placement of the distal screws as close as possible to the subchondral zone is crucial to maintain radial length after surgery. The purposes of this study were (1) to evaluate radial shortening after plating with regard to plate position and (2) to evaluate whether plate position has an influence on the strength and rigidity of the plate–screw construct.\ud \ud Methods: An extra-articular fracture (AO classification, A3) was created in 7 pairs of fresh-frozen human cadaver radiuses. The radiuses then were plated with a volar distal radius locking compression plate. Seven plates were applied subchondrally; 7 plates were applied 4.5 mm to 7.5 mm proximal to the subchondral zone. The specimens were loaded with 800-N loads for 2,000 cycles to evaluate radial shortening in the 2 groups. Each specimen then was loaded to failure.\ud \ud Results: Radial shortening was significantly greater when the distal screws were placed proximal to the subchondral zone. The amount of shortening after cyclic loading correlated significantly with the distance the distal screws were placed from the subchondral zone. Rigidity of the plate systems was significantly higher in radiuses in which the distal screws were placed close to the subchondral zone.\ud \ud Conclusions: To maintain radial length after volar fixed-angle plating, placement of the distal screws as subchondral as possible is essential. The subchondral plate–screw–bone constructs showed significantly greater rigidity, indicating higher resistance to postoperative loads and displacement forces

Essential Role for Protein Kinase D Family Kinases in the Regulation of Class II Histone Deacetylases in B Lymphocytes

We have taken a knockout approach to interrogate the function of protein kinase D (PKD) serine/threonine kinases in lymphocytes. DT40 B cells express two PKD family members, PKD1 and PKD3, which are both rapidly activated by the B-cell antigen receptor (BCR). DT40 cells with single or dual deletions of PKD1 and/or PKD3 were viable, allowing the role of individual PKD isoforms in BCR signal transduction to be assessed. One proposed downstream target for PKD1 in lymphocytes is the class II histone deacetylases (HDACs). Regulation of chromatin accessibility via class II histone deacetylases is an important mechanism controlling gene expression patterns, but the molecules that control this key process in B cells are not known. Herein, we show that phosphorylation and nuclear export of the class II histone deacetylases HDAC5 and HDAC7 are rapidly induced following ligation of the BCR or after treatment with phorbol esters (a diacylglycerol mimetic). Loss of either PKD1 or PKD3 had no impact on HDAC phosphorylation, but loss of both PKD1 and PKD3 abrogated antigen receptor-induced class II HDAC5/7 phosphorylation and nuclear export. These studies reveal an essential and redundant role for PKD enzymes in controlling class II HDACs in B lymphocytes and suggest that PKD serine kinases are a critical link between the BCR and epigenetic control of chromatin