No abstract

BackgroundRoot and tuber crops are a major food source in tropical Africa. Among these crops are several species in the monocotyledonous genus Dioscorea collectively known as yam, a staple tuber crop that contributes enormously to the subsistence and socio-cultural lives of millions of people, principally in West and Central Africa. Yam cultivation is constrained by several factors, and yam can be considered a neglected “orphan” crop that would benefit from crop improvement efforts. However, the lack of genetic and genomic tools has impeded the improvement of this staple crop.ResultsTo accelerate marker-assisted breeding of yam, we performed genome analysis of white Guinea yam (Dioscorea rotundata) and assembled a 594-Mb genome, 76.4% of which was distributed among 21 linkage groups. In total, we predicted 26,198 genes. Phylogenetic analyses with 2381 conserved genes revealed that Dioscorea is a unique lineage of monocotyledons distinct from the Poales (rice), Arecales (palm), and Zingiberales (banana). The entire Dioscorea genus is characterized by the occurrence of separate male and female plants (dioecy), a feature that has limited efficient yam breeding. To infer the genetics of sex determination, we performed whole-genome resequencing of bulked segregants (quantitative trait locus sequencing [QTL-seq]) in F1 progeny segregating for male and female plants and identified a genomic region associated with female heterogametic (male = ZZ, female = ZW) sex determination. We further delineated the W locus and used it to develop a molecular marker for sex identification of Guinea yam plants at the seedling stage.ConclusionsGuinea yam belongs to a unique and highly differentiated clade of monocotyledons. The genome analyses and sex-linked marker development performed in this study should greatly accelerate marker-assisted breeding of Guinea yam. In addition, our QTL-seq approach can be utilized in genetic studies of other outcrossing crops and organisms with highly heterozygous genomes. Genomic analysis of orphan crops such as yam promotes efforts to improve food security and the sustainability of tropical agriculture.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0419-x) contains supplementary material, which is available to authorized users.

During disease progression in myelodysplastic syndromes (MDS), clonal blasts gain a more aggressive nature, whereas nonclonal immune cells become less efficient via an unknown mechanism. Using MDS cell lines and patient samples, we showed that the expression of an immunoinhibitory molecule, B7-H1 (CD274), was induced by interferon-␥ (IFN␥) and tumor necrosis factor-␣ (TNF␣) on MDS blasts. This induction was associated with the activation of nuclear factor-B (NF-B) and nearly completely blocked by an NF-B inhibitor, pyrrolidine dithiocarbamate (PDTC). B7-H1 ؉ MDS blasts had greater intrinsic proliferative capacity than B7-H1 ؊ MDS blasts when examined in various assays. Furthermore, B7-H1 ؉ blasts suppressed T-cell proliferation and induced T-cell apoptosis in allogeneic cocultures. When fresh bone marrow samples from patients were examined, blasts from high-risk MDS patients expressed B7-H1 molecules more often compared with those from low-risk MDS patients. Moreover, MDS T cells often overexpressed programmed cell death 1 (PD-1) molecules that transmit an inhibitory signal from B7-H1 molecules. Taken IntroductionB7-H1 (CD274), which was identified by us as a costimulatory molecule, plays a crucial role in T-cell regulation in various immune responses. 1,2 B7-H1 molecules deliver a costimulatory signal through an unknown receptor on naive T cells. [1][2][3] They also deliver an inhibitory signal to activated T cells through programmed cell death 1 (PD-1) molecules, 4 which are a type I transmembrane protein belonging to the CD28 receptor family and were originally identified in T cells undergoing apoptosis. 5 B7-H1 expression is detected not only on antigenpresenting cells but also on activated T cells and some tumor cells (ie, renal cell, colon, breast, and lung carcinoma, and Hodgkin lymphoma). [6][7][8][9][10] Rodent data suggest that B7-H1 molecules on tumor cells deliver negative signals through PD-1 and other receptors on tumorspecific cytotoxic T lymphocytes and inhibit antitumor immune responses. 11,12 Consistent with those data, it was reported that in patients with renal cell carcinoma and breast cancer, patients whose tumor cells expressed B7-H1 had a poor prognosis. 9,13 In a mouse leukemia model in which mice were immunized with irradiated DA1-3b leukemia cells and then challenged with live DA1-3b cells, only leukemia cells expressing high levels of B7-H1 survived for a long period. Moreover, these cells gained tolerance to specific cytotoxic T lymphocytemediated killing. 14 Therefore, B7-H1 molecules on leukemia cells may be associated with immune evasion in this model.Myelodysplastic syndromes (MDS) are clonal hematologic stem cell disorders characterized by cytopenias, excessive apoptosis of hematopoietic cells, and a high risk of progression to acute myeloid leukemia (AML). In MDS, various immune abnormalities, including lymphopenia and T-cell dysfunction, have been reported, 15-17 although data on B7-related molecules, in particular B7-H1, are lacking. With disease progression, that is, with i...

Background-Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow. Methods and Results-We measured circulating CD34-positive mononuclear cells, activation of integrin Mac-1 on the surface of neutrophils, and plasma granulocyte-colony stimulating factor levels in 40 patients undergoing coronary stenting. After bare-metal stenting, CD34-positive cells increased, reaching a maximum on day 7 after stenting. The maximum change compared with baseline before stenting was more striking in patients with restenosis than without restenosis (332Ϯ108% versus 148Ϯ49%; PϽ0.05). In contrast, CD34-positive cells decreased after sirolimus-eluting stenting (72Ϯ21% on day 7). The change in CD34-positive cells on day 7 relative to baseline was closely correlated with that in activated Mac-1 at 48 hours (Rϭ0.52, PϽ0.01) and that in granulocyte-colony stimulating factor levels at 24 hours (Rϭ0.42, PϽ0.05). Cell culture assay on day 7 showed that mononuclear cells differentiated into CD31-positive endothelium-like cells after bare-metal stenting. In patients with restenosis, mononuclear cells differentiating into ␣-smooth muscle actin-positive smooth muscle-like cells also were observed. Implantation of sirolimus-eluting stents suppressed both types of differentiation. Conclusions-Stent