Project description:Data for the manuscript: Genomic and metabolomic analysis of the endophytic fungus Fusarium sp. VM-40 derived from the medicinal plant Vinca minor, authors: Ting He, Xiao Li, Riccardo Iacovelli, Thomas Hackl and Kristina Haslinger
Project description:Arteriovenous hemodialysis graft (AVG) stenosis results in thrombosis and AVG failure, and develops chiefly as a consequence of neotinimal hyperplasia (NH) formation in the graft-venous anastomosis region. Of note, the juxta-anastomotic vein regions are relatively resistant to NH. AVG stenosis has not been resolved partly due to our limited understanding of the molecular processes involved in the pathophysiology. We hypothesized that the gene expression profiles of the NH prone and NH-resistant regions will be different after graft placement, and analysis of their genomic profiles may yield therapeutic targets to address AVG stenosis. To test this hypothesis we evaluated the global genomic profiles of the graft-venous anastomosis (NH-prone) and juxta-anastomotic (NH-resistant) vein regions in a porcine model of AVG stenosis using a porcine microarray. Gene expression changes in these two distinct vein regions, relative to the gene expression in un-operated veins, were examined at an early (5 days) and later (14 days) time period following graft placement. Global genomic changes were much greater in the NH-prone region than in the NH-resistant region at both time points. In the NH-prone region, genes related to regulation of cell proliferation and osteo/chondrogenic vascular remodeling were most enriched among the significantly up-regulated genes at day 5 and day 14, respectively. At both time points, genes related to muscle phenotype were significantly down-regulated. These results provide insights into the spatial and temporal genomic modulation underlying NH formation in AVG, and suggest potential therapeutic strategies to prevent and/or limit AVG stenosis.
Project description:In mouse early pachytene spermatocytes, the X and Y chromosomes undergo rapid non-homologous (NH) synapsis and desynapsis, but the functional significance remains unknown. Here, we report that pachynema-specific knockout of Speedy A (SpdyA) from telomeres caused persistent Y-X NH synapsis, with the entire Y axis synapsed onto the X axis. This persistent Y-X NH synapsis did not interrupt meiotic sex chromosome inactivation, recombination, or sex body formation, but it disrupted X-Y loop-axis organization and homologous X-Y desynapsis, leading to spermatocyte death. Similarly, persistent Y-X NH synapsis was also observed in pachytene spermatocytes lacking TRF1, where SpdyA was frequently lost from X-Y non-pseudoautosomal region (non-PAR) telomeres. Mechanistic studies revealed that the Serine 48 of SUN1 is a key SpdyA/CDK2 phosphorylation site needed for Y-X NH desynapsis. We propose that SpdyA governs Y-X NH desynapsis by stabilizing the linkage between the X-Y non-PAR telomeres and their LINC complexes, and that this process is regulated independently from other aspects of pachynema progression. Our findings suggest a key role for Y-X NH desynapsis in establishing proper X-Y loop-axis organization.