Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia

Mesenchymal cell populations contribute to microenvironments regulating stem cells and the growth of malignant cells. Osteolineage cells participate in the hematopoietic stem cell niche. Here, we report that deletion of the miRNA processing endonuclease Dicer1 selectively in mesenchymal osteoprogenitors induces markedly disordered hematopoiesis. Hematopoietic changes affected multiple lineages recapitulating key features of human myelodysplastic syndrome (MDS) including the development of acute myelogenous leukemia. These changes were microenvironment dependent and induced by specific cells in the osteolineage. Dicer1−/− osteoprogenitors expressed reduced levels of Sbds, the gene mutated in the human bone marrow failure and leukemia predisposition Shwachman-Bodian-Diamond Syndrome. Deletion of Sbds in osteoprogenitors largely phenocopied Dicer1 deletion. These data demonstrate that differentiation stage-specific perturbations in osteolineage cells can induce complex hematological disorders and indicate the central role individual cellular elements of ‘estroma’ can play in tissue homeostasis. They reveal that primary changes in the hematopoietic microenvironment can initiate secondary neoplastic disease

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. Objectives We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. Methods A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p\0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not. Conclusion High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation

Small mammal community response to early meadow–forest succession

Abstract Background With farmland afforestation becoming common policy in many European Union countries, we studied how early forest succession (from meadow to young stand) influences small mammal species composition, diversity, abundance and biomass. Despite numerous investigations into forest succession, almost no attention has been given to the small mammal community change in the early-successional forest ecosystems, starting with the pre-forest habitat and ending with stand formation and the establishment of tree dominance. We compared small mammal communities in meadows at the initial stage of regrowth (with saplings less than 10 cm in height), in young forest (5–10 years old) and more advanced forest (15–20 years) in both cases of human-induced forest succession, where the trees had been planted, and natural forest succession, where natural regrowth of meadows had occurred. Results The greatest diversity of small mammal species was recorded in the meadow (H  =  2.95), with a lower diversity found in the young forest (H  =  2.61) and even lower in the advanced forest (H  =  2.04), the last habitat being the most monodominantic. The order of species dominance from Microtus sp. (M. arvalis, M. agrestis), Myodes glareolus, Apodemus flavicollis, Sorex araneus, A. agrarius in the meadow changed to M. glareolus, S. araneus, M. arvalis, M. agrestis in the young forest and to M. glareolus, A. flavicollis, S. araneus in the advanced forest. The lowest relative abundance of small mammals was recorded in the meadow (18.19  ±  2.27 ind. Per 100 trap-days), with Microtus voles being the most abundant. Relative abundance was higher in the young forest (22.72  ±  2.25 ind. Per 100 trap-days), with Myodes glareolus being the most abundant (7.59  ±  0.96 ind. Per 100 trap-days) and at its highest in the advanced forest (23.91  ±  2.77 ind. Per 100 trap-days), again with M. glareolus being the most abundant (15.54  ±  2.35 ind. Per 100 trap-days). Conclusions Thus, our analysis suggests that that during early meadow-forest succession, the diversity of the small mammal community declines – the number of species decreases as typical meadow species are lost due to the transformation of the habitat and one or a few species became dominants. However, the relative abundance of the small mammals increases. Biological indices of small mammal communities differed between natural and human-induced meadow-forest succession