Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags

Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance

Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked

Inorganic pyrophosphate as a regulator of hydroxyapatite or calcium pyrophosphate dihydrate mineral deposition by matrix vesicles

SummaryObjectivePathological mineralization is induced by unbalance between pro- and anti-mineralization factors. In calcifying osteoarthritic joints, articular chondrocytes undergo terminal differentiation similar to that in growth plate cartilage and release matrix vesicles (MVs) responsible for hydroxyapatite (HA) or calcium pyrophosphate dihydrate (CPPD) deposition. Inorganic pyrophosphate (PPi) is a likely source of inorganic phosphate (Pi) to sustain HA formation when hydrolyzed but also a potent inhibitor preventing apatite mineral deposition and growth. Moreover, an excess of PPi can lead to CPPD formation, a marker of pathological calcification in osteoarthritic joints. It was suggested that the Pi/PPi ratio during biomineralization is a turning point between physiological and pathological mineralization. The aim of this work was to determine the conditions favoring either HA or CPPD formation initiated by MVs.MethodsMVs were isolated from 17-day-old chicken embryo growth plate cartilages and subjected to mineralization in the presence of various Pi/PPi ratios. The mineralization kinetics and the chemical composition of minerals were determined, respectively, by light scattering and infrared spectroscopy.ResultsThe formation of HA is optimal when the Pi/PPi molar ratio is above 140, but is completely inhibited when the ratio decreases below 70. The retardation of any mineral formation is maximal at Pi/PPi ratio around 30. CPPD is exclusively produced by MVs when the ratio is below 6, but it is inhibited for the ratio exceeding 25.ConclusionsOur findings are consistent with the Pi/PPi ratio being a determinant factor leading to pathological mineralization or its inhibition

Inorganic pyrophosphate as a regulator of hydroxyapatite or calcium pyrophosphate dihydrate

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Potential role of annexin AnnAt1 from Arabidopsis thaliana in pH-mediated cellular response to environmental stimuli

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Crosstalk between tyrosine kinase receptors, GSK3 and BMP2 signaling during osteoblastic differentiation of human mesenchymal stem cells

International audienceBone morphogenic proteins (BMPs) promote mesenchymal stem cell (MSC) osteogenic differentiation, whereas platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) activate their proliferation through receptors tyrosine kinase (RTK). The effects of PDGF or FGF receptor signaling pathway on BMP2-induced osteoblastic differentiation was investigated in human MSC (HMSC). Inhibition of PDGF or/and FGF receptors enhanced BMP2-induced alkaline phosphatase (ALP) activity, expression of Osterix, ALP and Bone sialoprotein, and matrix calcification. These effects were associated with increased Smad-1 activity, indicating that mitogenic factors interfere with Smad signaling in HMSC differentiation. RTK activate MAPK and inhibit GSK3 through the PI3K/Akt pathway. Biochemical analysis indicated that MAPK JNK and GSK3 especially are potential signaling molecules regulating BMP-induced osteoblastic HMSC differentiation. These observations highlight that the osteogenic effects of BMP2 are modulated by mitogenic factors acting through RTK

Matrix vesicles originate from apical membrane microvilli of mineralizing osteoblast-like Saos-2 cells

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