The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis.

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(-/-) fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(-/-) fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(-/-). Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(-/-) phenotype

Cardiac transcriptional and metabolic changes following thoracotomy

Non-cardiac surgery is associated with significant cardiovascular complications. Reported mortality rate ranges from 1.9% to 4% in unselected patients. A postoperative surge in pro-inflammatory cytokines is a well-known feature and putative contributor to these complications. Despite much clinical research, little is known about the biomolecular changes in cardiac tissue following non-cardiac surgery. In order to increase our understanding, we analyzed whole-transcriptional and metabolic profiling data sets from hearts of mice harvested two, four, and six weeks following isolated thoracotomy. Hearts from healthy litter-mates served as controls. Functional network enrichment analyses showed a distinct impact on cardiac transcription two weeks after surgery characterized by a downregulation of mitochondrial pathways in the absence of significant metabolic alterations. Transcriptional changes were not detectable four and six weeks following surgery. Our study shows distinct and reversible transcriptional changes within the first two weeks following isolated thoracotomy. This coincides with a time period, in which most cardiovascular events happen

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects

Minimum Information about a Biosynthetic Gene cluster

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.Chemistry and Chemical Biolog

Barren magnetite breccias in the Cloncurry region, Australia: comparisons to IOCG deposits

We have examined unmineralized and weakly mineralized magnetite-matrix hydrothermal breccias from the Cloncurry region, Australia. These breccias are similar in texture and mineralogy to regional and international IOCG deposits. Comparing mineralized and barren hydrothermal breccias affords a rare opportunity to define the critical factors that must be present to generate economic Cu-Au mineralization. Such comparisons also may lead to geochemical features that fingerprint mineralization. Here we compare rock textures, mineralogy, magnetite trace element geochemistry, and fluid inclusion petrography and geochemistry among barren magnetite breccias and IOCG deposits from Australia and Brazil. Magnetite from barren breccias is enriched in V and depleted in Mn relative to ore-related magnetite from Ernest Henry Cu-Au deposit. In contrast, fluid inclusion compositions in the barren breccias are similar to compositions of fluids from the Carajas IOCG deposits, Brazil, both of which differ markedly from brines related to porphyry copper mineralization. The similarity in brine composition between IOCG fluids and fluids from barren magnetite breccias suggests similar brine sources and fluid-rock reaction pathways for both mineralized and unmineralized systems, while the difference in magnetite chemistry may result from mineral equilibrium assemblage at the site of magnetite deposition