A GBF1-Dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport

How can anterograde membrane trafficking be modulated by physiological cues? A screen of Golgi-associated proteins revealed that the ARF-GEF GBF1 can selectively modulate the ER-Golgi trafficking of prohaemostatic von Willebrand factor (VWF) and extracellular matrix (ECM) proteins in human endothelial cells and in mouse fibroblasts. The relationship between levels of GBF1 and the trafficking of VWF into forming secretory granules confirmed GBF1 is a limiting factor in this process. Further, GBF1 activation by AMPK couples its control of anterograde trafficking to physiological cues; levels of glucose control GBF1 activation in turn modulating VWF trafficking into secretory granules. GBF1 modulates both ER and TGN exit, the latter dramatically affecting the size of the VWF storage organelles, thereby influencing the hemostatic capacity of the endothelium. The role of AMPK as a central integrating element of cellular pathways with intra- and extra-cellular cues can now be extended to modulation of the anterograde secretory pathway

Changes in the geographical distribution of plant species and climatic variables on the West Cornwall peninsula (South West UK)

Recent climate change has had a major impact on biodiversity and has altered the geographical distribution of vascular plant species. This trend is visible globally; however, more local and regional scale research is needed to improve understanding of the patterns of change and to develop appropriate conservation strategies that can minimise cultural, health, and economic losses at finer scales. Here we describe a method to manually geo-reference botanical records from a historical herbarium to track changes in the geographical distributions of plant species in West Cornwall (South West England) using both historical (pre-1900) and contemporary (post-1900) distribution records. We also assess the use of Ellenberg and climate indicator values as markers of responses to climate and environmental change. Using these techniques we detect a loss in 19 plant species, with 6 species losing more than 50% of their previous range. Statistical analysis showed that Ellenberg (light, moisture, nitrogen) and climate indicator values (mean January temperature, mean July temperature and mean precipitation) could be used as environmental change indicators. Significantly higher percentages of area lost were detected in species with lower January temperatures, July temperatures, light, and nitrogen values, as well as higher annual precipitation and moisture values. This study highlights the importance of historical records in examining the changes in plant species’ geographical distributions. We present a method for manual geo-referencing of such records, and demonstrate how using Ellenberg and climate indicator values as environmental and climate change indicators can contribute towards directing appropriate conservation strategies

The Shear Stress-Induced Transcription Factor KLF2 Affects Dynamics and Angiopoietin-2 Content of Weibel-Palade Bodies

BACKGROUND: The shear-stress induced transcription factor KLF2 has been shown to induce an atheroprotective phenotype in endothelial cells (EC) that are exposed to prolonged laminar shear. In this study we characterized the effect of the shear stress-induced transcription factor KLF2 on regulation and composition of Weibel-Palade bodies (WPBs) using peripheral blood derived ECs. METHODOLOGY AND PRINCIPAL FINDINGS: Lentiviral expression of KLF2 resulted in a 4.5 fold increase in the number of WPBs per cell when compared to mock-transduced endothelial cells. Unexpectedly, the average length of WPBs was significantly reduced: in mock-transduced endothelial cells WPBs had an average length of 1.7 µm versus 1.3 µm in KLF2 expressing cells. Expression of KLF2 abolished the perinuclear clustering of WPBs observed following stimulation with cAMP-raising agonists such as epinephrine. Immunocytochemistry revealed that WPBs of KLF2 expressing ECs were positive for IL-6 and IL-8 (after their upregulation with IL-1β) but lacked angiopoietin-2 (Ang2), a regular component of WPBs. Stimulus-induced secretion of Ang2 in KLF2 expressing ECs was greatly reduced and IL-8 secretion was significantly lower. CONCLUSIONS AND SIGNIFICANCE: These data suggest that KLF2 expression leads to a change in size and composition of the regulated secretory compartment of endothelial cells and alters its response to physiological stimuli