Foxtail millet (Setaria italica) is an important grain crop that is grown in arid regions. Here we sequenced 916 diverse foxtail millet varieties, identified 2.58 million SNPs and used 0.8 million common SNPs to construct a haplotype map of the foxtail millet genome. We classified the foxtail millet varieties into two divergent groups that are strongly correlated with early and late flowering times. We phenotyped the 916 varieties under five different environments and identified 512 loci associated with 47 agronomic traits by genome-wide association studies. We performed a de novo assembly of deeply sequenced genomes of a Setaria viridis accession (the wild progenitor of S. italica) and an S. italica variety and identified complex interspecies and intraspecies variants. We also identified 36 selective sweeps that seem to have occurred during modern breeding. This study provides fundamental resources for genetics research and genetic improvement in foxtail millet.

The purpose of this study was to noninvasively monitor tumor oxygenation and redox status during hyperoxygenation treatment, such as carbogen-breathing, in a murine tumor model using in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging techniques. The study was performed using implanted lithium phthalocyanine (LiPc) microcrystals as the oximetry probe and 3-carbamoylproxyl ( Since tumor oxygenation is known to enhance the efficacy of radiotherapy, numerous experimental and clinical strategies have been introduced to improve it. A recent strategy combines breathing of carbogen gas (a mixture of 95% oxygen and 5% CO 2 ) with administration of nicotinamide (1). This combination is selected to specifically target the two major types of hypoxia thought to exist in tumors: 1) chronic hypoxia, which results from diffusion limitations of oxygen; and 2) acute hypoxia, which is caused by the intermittent constriction of tumor blood vessels. Carbogen is believed to increase the oxygen content of the blood while at the same time it promotes vasodilation based on its 5% CO 2 content. Nicotinamide is believed to reduce intermittent vessel closures (2). Using a combination of both carbogen and nicotinamide, studies have shown that oxygenation, and hence the sensitivity to radiotherapy, have been significantly enhanced in both single-dose (3) and fractionated regimens (4 -6). While these and most other studies have shown beneficial effects of carbogenbreathing on tumor oxygenation, it has also been shown in a few studies that carbogen-breathing produces variable oxygenation results (7,8). For example, in a recent report, Dewhirst et al. (8) reported that carbogen had no consistent effect on tumor blood flow and was ineffective at increasing pO 2 in R3230Ac tumors in rat. Their laser Doppler flow measurements showed that the tumor blood flow effects are not global but occur at the microregional level. Thus, irrespective of the tumor model, treatment modality, or outcome, a direct quantitative determination of tumor oxygenation will greatly aid in the evaluation of the tumor microenvironment.Methods used to measure oxygen concentration (termed "oximetry") or hypoxia in tumors have received considerable attention (9 -11). These methods include polarographic oxygen electrodes, comet assay, immunochemical techniques, optical spectroscopy, 19 F magnetic resonance spectroscopy (MRS) and imaging (MRI), 31 P-MRS, and electron paramagnetic resonance (EPR) spectroscopy and imaging. However, concerns regarding invasiveness, insufficient dynamic range of measurements, requirements for repetitive measurements, and poor spatial or temporal resolution have limited the realization of the full potential of these techniques. The polarographic oxygen electrode, often considered as the gold standard, is invasive, subject to pressure artifacts, and unsuitable for repeated measurements. Magnetic resonance techniques (MRI, blood oxygen level dependent (BOLD), Overhauser-enhanced MRI (OMRI), and EPR) and positron emission tomography (...

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As an ancient cereal of great importance for dryland agriculture even today, foxtail millet (Setaria italica) is fast becoming a new plant genomic model crop. A genotypic analysis of 250 foxtail millet landraces, which represent 1% of foxtail millet germplasm kept in the Chinese National Gene Bank (CNGB), was conducted with 77 SSRs covering the foxtail millet genome. A high degree of molecular diversity among the landraces was found, with an average of 20.9 alleles per locus detected. STRUCTURE, neighbor-jointing, and principal components analyses classify the accessions into three clusters (topmost hierarchy) and, ultimately, four conservative subgroups (substructuring within the topmost clusters) in total, which are in good accordance with eco-geographical distribution in China. The highest subpopulation diversity was identified in the accessions of Pop3 from the middle regions of the Yellow River, followed by accessions in Pop1 from the downstream regions of the Yellow River, suggesting that foxtail millet was domesticated in the Yellow River drainage area first and then spread to other parts of the country. Linkage disequilibrium (LD) decay of less than 20 cM of genetic distance in the foxtail millet landrace genome was observed, which suggests that it could be possible to achieve resolution down to the 20 cM level for association mapping.

Transporters move hydrophilic substrates across hydrophobic biological membranes and play key roles in plant nutrition, metabolism, and signaling and, consequently, in plant growth, development, and responses to the environment. To initiate and support systematic characterization of transporters in the model legume Medicago truncatula, we identified 3,830 transporters and classified 2,673 of these into 113 families and 146 subfamilies. Analysis of gene expression data for 2,611 of these transporters identified 129 that are expressed in an organ-specific manner, including 50 that are nodule specific and 36 specific to mycorrhizal roots. Further analysis uncovered 196 transporters that are induced at least 5-fold during nodule development and 44 in roots during arbuscular mycorrhizal symbiosis. Among the nodule-and mycorrhiza-induced transporter genes are many candidates for known transport activities in these beneficial symbioses. The data presented here are a unique resource for the selection and functional characterization of legume transporters.

BackgroundThe emergence of precision medicine allowed the incorporation of individual molecular data into patient care. Indeed, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery.Method‘N-of-1-pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the deregulated pathways of each patient.ResultsCross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03).ConclusionsThe N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies.Softwarehttp://lussierlab.org/publications/N-of-1-pathways