The ancestors of Gossypium arboreum and Gossypium herbaceum provided the A subgenome for the modern cultivated allotetraploid cotton. Here, we upgraded the G. arboreum genome assembly by integrating different technologies. We resequenced 243 G. arboreum and G. herbaceum accessions to generate a map of genome variations and found that they are equally diverged from Gossypium raimondii. Independent analysis suggested that Chinese G. arboreum originated in South China and was subsequently introduced to the Yangtze and Yellow River regions. Most accessions with domestication-related traits experienced geographic isolation. Genome-wide association study (GWAS) identified 98 significant peak associations for 11 agronomically important traits in G. arboreum. A nonsynonymous substitution (cysteine-to-arginine substitution) of GaKASIII seems to confer substantial fatty acid composition (C16:0 and C16:1) changes in cotton seeds. Resistance to fusarium wilt disease is associated with activation of GaGSTF9 expression. Our work represents a major step toward understanding the evolution of the A genome of cotton.

Upland cotton is the most important natural-fiber crop. The genomic variation of diverse germplasms and alleles underpinning fiber quality and yield should be extensively explored. Here, we resequenced a core collection comprising 419 accessions with 6.55-fold coverage depth and identified approximately 3.66 million SNPs for evaluating the genomic variation. We performed phenotyping across 12 environments and conducted genome-wide association study of 13 fiber-related traits. 7,383 unique SNPs were significantly associated with these traits and were located within or near 4,820 genes; more associated loci were detected for fiber quality than fiber yield, and more fiber genes were detected in the D than the A subgenome. Several previously undescribed causal genes for days to flowering, fiber length, and fiber strength were identified. Phenotypic selection for these traits increased the frequency of elite alleles during domestication and breeding. These results provide targets for molecular selection and genetic manipulation in cotton improvement.

Key Points• Risk stratification treatment of t(8;21) acute myeloid leukemia may decrease relapse and improve longterm survival.• Allo-HSCT benefited high-risk patients, but impaired the survival of low-risk patients.We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P 5 .001).Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P 5 .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR- OCH-12002406. (Blood. 2013;121(20):4056-4062)

Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.

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MYC2 is a core transcription factor in the plant response to jasmonates. It also functions in secondary metabolism and various processes for growth and development. However, the knowledge about its role in Salvia miltiorrhiza is still very limited. We determined that the biosynthesis of salvianolic acid B (Sal B) was strongly induced in 2-month-old transgenic plants that over-expressed SmMYC2. In the roots of transgenic line 12 that over-expressed SmMYC2 (OEM-12), the Sal B concentration was as high as 5.95 ± 0.07 mg g-1, a level that was 1.88-fold higher than that in control plants that had been transformed with an empty vector. Neither tanshinone IIA nor cryptotanshinone was detected by high-performance liquid chromatography in any of the genotypes. Global transcriptomic analysis using RNA sequencing revealed that most enzyme-encoding genes for the phenylpropanoid biosynthesis pathway were up-regulated in the overexpression lines. Furthermore, both the phenylalanine and tyrosine biosynthesis pathways were activated in those transgenics. Our data demonstrate that overexpression of SmMYC2 promotes the production of phenolic acids by simultaneously activating both primary and secondary pathways for metabolism in S. miltiorrhiza.

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Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.