RESUMEN
Most Ralstonia solanacearum species complex strains cause bacterial wilts in tropical or subtropical zones, but the group known as Race 3 biovar 2 (R3bv2) is cool virulent and causes potato brown rot at lower temperatures. R3bv2 has invaded potato-growing regions around the world but is not established in the United States. Phylogenetically, R3bv2 corresponds to a subset of the R. solanacearum phylotype IIB clade, but little is known about the distribution of the cool virulence phenotype within phylotype IIB. Therefore, genomes of 76 potentially cool virulent phylotype IIB strains and 30 public genomes were phylogenetically analyzed. A single clonal lineage within the sequevar 1 subclade of phylotype IIB that originated in South America has caused nearly all brown rot outbreaks worldwide. To correlate genotypes with relevant phenotypes, we quantified virulence of ten Ralstonia strains on tomato and potato at both 22°C and 28°C. Cool virulence on tomato did not predict cool virulence on potato. We found that cool virulence is a quantitative trait. Strains in the sequevar 1 pandemic clonal lineage caused the most disease, while other R3bv2 strains were only moderately cool virulent. However, some non-R3bv2 strains were highly cool virulent and aggressively colonized potato tubers. Thus, cool virulence is not consistently correlated with strains historically classified as R3bv2 group. To aid detection of sequevar 1 strains, this group was genomically delimited in the LINbase web server and a sequevar 1 diagnostic primer pair was developed and validated. We discuss implications of these results for the R3bv2 definition.
RESUMEN
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is characterized by the accumulation of intracellular neurofibrillary tangles, extracellular amyloid plaques, and neuroinflammation. In partnership with microglial cells, astrocytes are key players in the regulation of neuroinflammation. Fatty acid binding protein 7 (FABP7) belongs to a family of conserved proteins that regulate lipid metabolism, energy homeostasis, and inflammation. FABP7 expression is largely restricted to astrocytes and radial glia-like cells in the adult central nervous system. We observed that treatment of primary hippocampal astrocyte cultures with amyloid ß fragment 25-35 (Aß25-35) induces FABP7 upregulation. In addition, FABP7 expression is upregulated in the brain of APP/PS1 mice, a widely used AD mouse model. Co-immunostaining with specific astrocyte markers revealed increased FABP7 expression in astrocytes. Moreover, astrocytes surrounding amyloid plaques displayed increased FABP7 staining when compared to non-plaque-associated astrocytes. A similar result was obtained in the brain of AD patients. Whole transcriptome RNA sequencing analysis of human astrocytes differentiated from induced pluripotent stem cells (i-astrocytes) overexpressing FABP7 identified 500 transcripts with at least a 2-fold change in expression. Gene Ontology enrichment analysis identified (i) positive regulation of cytokine production and (ii) inflammatory response as the top two statistically significant overrepresented biological processes. We confirmed that wild-type FABP7 overexpression induces an NF-κB-driven inflammatory response in human i-astrocytes. On the other hand, the expression of a ligand-binding impaired mutant FABP7 did not induce NF-κB activation. Together, our results suggest that the upregulation of FABP7 in astrocytes could contribute to the neuroinflammation observed in AD.