Hierarchical multiple-factor analysis for classifying genotypes based on phenotypic and genetic data

A numerical classifi cation problem encountered by breeders and gene-bank curators is how to partition the original heterogeneous population of genotypes into non-overlapping homogeneous subpopulations. The measure of distance that may be defi ned depends on the type of variables measured (i.e., continuous and/or discrete). The key points are whether and how a distance may be defi ned using all types of variables to achieve effective classifi cation. The objective of this research was to propose an approach that combines the use of hierarchical multiple-factor analysis (HMFA) and the two-stage Ward Modifi ed Location Model (Ward-MLM) classifi cation strategy that allows (i) combining different types of phenotypic and genetic data simultaneously; (ii) balancing out the effects of the different phenotypic, genetic, continuous, and discrete variables; and (iii) measuring the contribution of each original variable to the new principal axes (PAs). Of the two strategies applied for developing PA scores to be used for clustering genotypes, the strategy that used the fi rst few PA scores to which phenotypic and genetic variables each contributed 50% (i.e., a balanced contribution) formed better groups than those formed by the strategy that used a large number of PA scores explaining 95% of total variability. Phenotypic variables account for much variability in the initial PA; then their contributions decrease. The importance of genetic variables increases in later PAs. Results showed that various phenotypic and genetic variables made important contributions to the new PA. The HMFA uses all phenotypic and genetic variables simultaneously and, in conjunction with the Ward-MLM method, it offers an effective unifying approach for the classifi cation of breeding genotypes into homogeneous groups and for the formation of core subsets for genetic resource conservation

Calculation of two-loop virtual corrections to b --> s l+ l- in the standard model

We present in detail the calculation of the virtual O(alpha_s) corrections to the inclusive semi-leptonic rare decay b --> s l+ l-. We also include those O(alpha_s) bremsstrahlung contributions which cancel the infrared and mass singularities showing up in the virtual corrections. In order to avoid large resonant contributions, we restrict the invariant mass squared s of the lepton pair to the range 0.05 < s/mb^2 < 0.25. The analytic results are represented as expansions in the small parameters s/mb^2, z = mc^2/mb^2 and s/(4 mc^2). The new contributions drastically reduce the renormalization scale dependence of the decay spectrum. For the corresponding branching ratio (restricted to the above s-range) the renormalization scale uncertainty gets reduced from +/-13% to +/-6.5%.Comment: 41 pages including 9 postscript figures; in version 2 some typos and inconsistent notation correcte

Population genomic and genome-wide association studies of agroclimatic traits in sorghum

Accelerating crop improvement in sorghum, a staple food for people in semiarid regions across the developing world, is key to ensuring global food security in the context of climate change. To facilitate gene discovery and molecular breeding in sorghum, we have characterized ∼265,000 single nucleotide polymorphisms (SNPs) in 971 worldwide accessions that have adapted to diverse agroclimatic conditions. Using this genome-wide SNPmap,we have characterized population structure with respect to geographic origin and morphological type and identified patterns of ancient crop diffusion to diverse agroclimatic regions across Africa and Asia. To better understand the genomic patterns of diversification in sorghum, we quantified variation in nucleotide diversity, linkage disequilibrium, and recombination rates across the genome. Analyzing nucleotide diversity in landraces, we find evidence of selective sweeps around starch metabolism genes, whereas in landrace-derived introgression lines, we find introgressions around known height and maturity loci. To identify additional loci underlying variation in major agroclimatic traits, we performed genome-wide association studies (GWAS) on plant height components and inflorescence architecture. GWAS maps several classical loci for plant height, candidate genes for inflorescence architecture. Finally, we trace the independent spread of multiple haplotypes carrying alleles for short stature or long inflorescence branches. This genome-wide map of SNP variation in sorghum provides a basis for crop improvement through marker-assisted breeding and genomic selection

Image quality and diagnostic accuracy of unenhanced SSFP MR angiography compared with conventional contrast-enhanced MR angiography for the assessment of thoracic aortic diseases

The purpose of this study was to determine the image quality and diagnostic accuracy of three-dimensional (3D) unenhanced steady state free precession (SSFP) magnetic resonance angiography (MRA) for the evaluation of thoracic aortic diseases. Fifty consecutive patients with known or suspected thoracic aortic disease underwent free-breathing ECG-gated unenhanced SSFP MRA with non-selective radiofrequency excitation and contrast-enhanced (CE) MRA of the thorax at 1.5 T. Two readers independently evaluated the two datasets for image quality in the aortic root, ascending aorta, aortic arch, descending aorta, and origins of supra-aortic arteries, and for abnormal findings. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined for both datasets. Sensitivity, specificity, and diagnostic accuracy of unenhanced SSFP MRA for the diagnosis of aortic abnormalities were determined. Abnormal aortic findings, including aneurysm (n = 47), coarctation (n = 14), dissection (n = 12), aortic graft (n = 6), intramural hematoma (n = 11), mural thrombus in the aortic arch (n = 1), and penetrating aortic ulcer (n = 9), were confidently detected on both datasets. Sensitivity, specificity, and diagnostic accuracy of SSFP MRA for the detection of aortic disease were 100% with CE-MRA serving as a reference standard. Image quality of the aortic root was significantly higher on SSFP MRA (P &lt; 0.001) with no significant difference for other aortic segments (P &gt; 0.05). SNR and CNR values were higher for all segments on SSFP MRA (P &lt; 0.01). Our results suggest that free-breathing navigator-gated 3D SSFP MRA with non-selective radiofrequency excitation is a promising technique that provides high image quality and diagnostic accuracy for the assessment of thoracic aortic disease without the need for intravenous contrast material

THE DATA REDUCTION PIPELINE FOR THE APACHE POINT OBSERVATORY GALACTIC EVOLUTION EXPERIMENT

The Apache Point Observatory Galactic Evolution Experiment (APOGEE), part of the Sloan Digital Sky Survey III, explores the stellar populations of the Milky Way using the Sloan 2.5-m telescope linked to a high resolution (R ~ 22,500), near-infrared (1.51–1.70 µm) spectrograph with 300 optical fibers. For over 150,000 predominantly red giant branch stars that APOGEE targeted across the Galactic bulge, disks and halo, the collected high signal-to-noise ratio (>100 per half-resolution element) spectra provide accurate (~0.1 km s-1) RVs, stellar atmospheric parameters, and precise (lesssim0.1 dex) chemical abundances for about 15 chemical species. Here we describe the basic APOGEE data reduction software that reduces multiple 3D raw data cubes into calibrated, well-sampled, combined 1D spectra, as implemented for the SDSS-III/APOGEE data releases (DR10, DR11 and DR12). The processing of the near-IR spectral data of APOGEE presents some challenges for reduction, including automated sky subtraction and telluric correction over a 3°-diameter field and the combination of spectrally dithered spectra. We also discuss areas for future improvement

Consumer acculturation theory: (crossing) conceptual boundaries

Consumer acculturation theorists have developed an insightful body of literature about the ways in which migrants adapt to foreign cultures via consumption. The present paper revisits 14 key studies from this field to highlight its most important contributions, critique its conceptual boundaries, and present cases of conceptual border crossings that indicate an emerging need for a broader conceptualization of the phenomenon. The paper closes by introducing a model that frames consumer acculturation as a complex system of recursive socio-cultural adaptation, and discusses its implications for future research

Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of <it>Plasmodium </it><it>falciparum </it>through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration.</p> <p>Results</p> <p>Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle.</p> <p>Conclusions</p> <p>We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c), a Zinc finger transcription factor (PFL0465c) both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c).</p

Receptor-Mediated Enhancement of Beta Adrenergic Drug Activity by Ascorbate In Vitro and In Vivo

RATIONALE: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also measured. Dose response curves were determined for the effect of albuterol plus-and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS: Ascorbate binds to the beta 2 adrenergic receptor at physiological concentrations. The receptor recycles dehydroascorbate. Physiological and supra-physiological concentrations of ascorbate enhance submaximal epinephrine and isoproterenol relaxation of trachealis, producing a 3-10-fold increase in sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate improves albuterol's effect on heaves and produces a 10-fold enhancement of albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta-adrenergic activity via a novel receptor-mediated mechanism; increases potency and duration of beta adrenergic agonists effective in asthma and COPD; prevents tachyphylaxis; and reverses fade. These novel effects are probably caused by a novel mechanism involving phosphorylation of aminergic receptors and have clinical and drug-development applications