44 research outputs found
The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection
Autoantibodies to components of apoptotic cells, such as anti-perlecan antibodies, contribute to rejection in organ
transplant recipients. However, mechanisms of immunization to apoptotic components remain largely uncharacterized. We used large-scale proteomics, with validation by electron microscopy and biochemical methods, to compare
the protein profiles of apoptotic bodies and apoptotic exosome-like vesicles, smaller extracellular vesicles released
by endothelial cells downstream of caspase-3 activation. We identified apoptotic exosome-like vesicles as a central
trigger for production of anti-perlecan antibodies and acceleration of rejection. Unlike apoptotic bodies, apoptotic
exosome-like vesicles triggered the production of anti-perlecan antibodies in naĂŻve mice and enhanced anti-perlecan
antibody production and allograft inflammation in mice transplanted with an MHC (major histocompatibility
complex)–incompatible aortic graft. The 20S proteasome core was active within apoptotic exosome-like vesicles
and controlled their immunogenic activity. Finally, we showed that proteasome activity in circulating exosome-like
vesicles increased after vascular injury in mice. These findings open new avenues for predicting and controlling maladaptive humoral responses to apoptotic cell components that enhance the risk of rejection after transplantation
Is there a link between proprotein convertase PC7 activity and human lipid homeostasis?
A genome-wide association study suggested that a R504H mutation in the proprotein convertase PC7 is associated with increased circulating levels of HDL and reduced triglycerides in black Africans. Our present results show that PC7 and PC7-R504H exhibit similar processing of transferrin receptor-1, proSortilin, and apolipoprotein-F. Plasma analyses revealed no change in the lipid profiles, insulin or glucose of wild type and PC7 KO mice. Thus, the R504H mutation does not modify the proteolytic activity of PC7. The mechanisms behind the implication of PC7 in the regulation of human HDL, triglycerides and in modifying the levels of atherogenic small dense LDL remain to be elucidated
IT_RPB1_MJB
Phylip file of Onnia tomentosa, individual sequence of carpophore
Recent advances related to poplar leaf spot and canker caused by Septoria musiva
The expansion of poplar culture in the north-central and northeastern regions of North America has been limited because many poplar clones are susceptible to the leaf spot and canker disease caused by the fungus Septoria musiva (teleomorph Mycosphaerella populorum). This review provides a brief historical account and summarizes the current state of knowledge focussing on developments in the areas of taxonomy and systematics, host associations and symptomatology. Since selection and deployment of resistant clones is one of the best disease-control strategies against S. musiva, recent advances in our knowledge of epidemiology, genetics and variability in virulence and aggressiveness of the populations of this fungus are also addressed
Recent advances related to poplar leaf spot and canker caused by Septoria musiva
The expansion of poplar culture in the north-central and northeastern regions of North America has been limited because many poplar clones are susceptible to the leaf spot and canker disease caused by the fungus Septoria musiva (teleomorph Mycosphaerella populorum). This review provides a brief historical account and summarizes the current state of knowledge focussing on developments in the areas of taxonomy and systematics, host associations and symptomatology. Since selection and deployment of resistant clones is one of the best disease-control strategies against S. musiva, recent advances in our knowledge of epidemiology, genetics and variability in virulence and aggressiveness of the populations of this fungus are also addressed
Data from: Patterns of colonization and spread in the fungal spruce pathogen Onnia tomentosa
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Data from: Patterns of colonization and spread in the fungal spruce pathogen Onnia tomentosa
The basidiomycetous fungus Onnia tomentosa is one of the most widespread root rot pathogens in North America. Although the disease is more severe on spruce and pine trees, this pathogen can infect several coniferous species. In order to study the population structure of O. tomentosa, we harvested 180 basidiocarps in a 45-year-old white spruce plantation in western Quebec in autumn 1997, and extracted DNA directly from individual basidiocarps. Using a combination of spatial coordinates and molecular data based on the analysis of two mitochondrial and three nuclear loci, we measured the average genet size and molecular diversity and assessed the relative contribution of basidiospores and vegetative growth to the stand colonization. Most of the sampled basidiocarps that clustered spatially belonged to the same genet. A total of thirty-seven discrete multilocus genets of an average size of 3.42 m were obtained. The genet size distribution was skewed toward smaller genets ( 3 m). The nuclear loci were in Hardy-Weinberg equilibrium in the larger genets, but not in the smaller genets, which displayed a deficiency of heterozygotes. This suggests a Wahlund effect, whereby different colonization events resulted in expected heterozygosity higher than observed heterozygosity. Using an estimate of the growth rate of the fungus, only a few of the largest genets were approximately the age of the plantation. These observations are consistent with the colonization by basidiospores subsequent to site preparation and tree planting followed by secondary colonization events and vegetative spread
Genome-enhanced detection and identification of fungal pathogens responsible for pine and poplar rust diseases.
Biosurveillance is a proactive approach that may help to limit the spread of invasive fungal pathogens of trees, such as rust fungi which have caused some of the world's most damaging diseases of pines and poplars. Most of these fungi have a complex life cycle, with up to five spore stages, which is completed on two different hosts. They have a biotrophic lifestyle and may be propagated by asymptomatic plant material, complicating their detection and identification. A bioinformatics approach, based on whole genome comparison, was used to identify genome regions that are unique to the white pine blister rust fungus, Cronartium ribicola, the poplar leaf rust fungi Melampsora medusae and Melampsora larici-populina or to members of either the Cronartium and Melampsora genera. Species- and genus-specific real-time PCR assays, targeting these unique regions, were designed with the aim of detecting each of these five taxonomic groups. In total, twelve assays were developed and tested over a wide range of samples, including different spore types, different infected plant parts on the pycnio-aecial or uredinio-telial host, and captured insect vectors. One hundred percent detection accuracy was achieved for the three targeted species and two genera with either a single assay or a combination of two assays. This proof of concept experiment on pine and poplar leaf rust fungi demonstrates that the genome-enhanced detection and identification approach can be translated into effective real-time PCR assays to monitor tree fungal pathogens
Deletion of the Gene Encoding Proprotein Convertase 5/6 Causes Early Embryonic Lethality in the Mouse
PC5 belongs to the proprotein convertase family and activates precursor proteins by cleavage at basic sites during their transit through the secretory pathway and/or at the cell surface. These precursors include prohormones, proreceptors, growth factors, adhesion molecules, and viral glycoproteins. The Pcsk5 gene encodes two alternatively spliced isoforms, the soluble PC5A and transmembrane PC5B. We have carefully analyzed the expression of PC5 in the mouse during development and in adulthood by in situ hybridization, as well as in mouse tissues and various cell lines by quantitative reverse transcription-PCR. The data show that adrenal cortex and intestine are the richest sources of PC5A and PC5B, respectively. To better define the specific physiological roles of PC5, we have generated a mouse Pcsk5(Δ4)-deficient allele missing exon 4 that encodes the catalytic Asp(173). While Δ4/+ heterozygotes were healthy and fertile, genotyping of progeny obtained from Δ4/+ interbreeding indicated that Δ4/Δ4 embryos died between embryonic days 4.5 and 7.5. These data demonstrate that Pcsk5 is an essential gene