Isolation and extraction of lucidin primeveroside from Rubia tinctorum L. and crystal structure elucidation

Madder (Rubia tinctorum L.) has been used as a dye for over 2000 years with alizarin and purpurin the major natural dyes analysed from extractions undertaken. The use of ethanol as the solvent in the extraction process produced an extract that yielded four anthraquinone compounds lucidin primeveroside, ruberythric acid, alizarin and lucidin-ω-ethyl ether. Gravitational separation of the extract was used to record the first crystal structure of lucidin primeveroside, which is also the first ever known crystal structure of a glycoside containing anthraquinone moiety. The crystal structure along with 1H and 13C NMR helped elucidate and confirm the structure of this overlooked natural dye which has been shown to be a major compound in R. tinctorum L

Inclusion of genetically identical animals to a numerator relationship matrix and modification of its inverse

In the field of animal breeding, estimation of genetic parameters and prediction of breeding values are routinely conducted by analyzing quantitative traits. Using an animal model and including the direct inverse of a numerator relationship matrix (NRM) into a mixed model has made these analyses possible. However, a method including a genetically identical animal (GIA) in NRM if genetic relationships between pairs of GIAs are not perfect, is still lacking. Here, we describe a method to incorporate GIAs into NRM using a K matrix in which diagonal elements are set to 1.0, off-diagonal elements between pairs of GIAs to (1-x) and the other elements to 0, where x is a constant less than 0.05. The inverse of the K matrix is then calculated directly by a simple formula. Thus, the inverse of the NRM is calculated by the products of the lower triangular matrix that identifies the parents of each individual, its transpose matrix, the inverse of the K matrix and the inverse of diagonal matrix D, in which the diagonal elements comprise a number of known parents and their inbreeding coefficients. The computing method is adaptable to the analysis of a data set including pairs of GIAs with imperfect relationships

Genetic prediction of complex traits: integrating infinitesimal and marked genetic effects

Genetic prediction for complex traits is usually based on models including individual (infinitesimal) or marker effects. Here, we concentrate on models including both the individual and the marker effects. In particular, we develop a ''Mendelian segregation'' model combining infinitesimal effects for base individuals and realized Mendelian sampling in descendants described by the available DNA data. The model is illustrated with an example and the analyses of a public simulated data file. Further, the potential contribution of such models is assessed by simulation. Accuracy, measured as the correlation between true (simulated) and predicted genetic values, was similar for all models compared under different genetic backgrounds. As expected, the segregation model is worthwhile when markers capture a low fraction of total genetic variance. (Résumé d'auteur

Gaggle on the Gavel: Designing an Interactive Website to Create a Community of Lawyers

Law is behind other industries and professions in its implementation of technolo-gy that could make the practice of law and the delivery of legal services more ef-fective and satisfying. Although there has been considerable development in le-gal technology over the past few years, research identified the need for an interac-tive LinkedIn-style online community for lawyers to communicate other lawyers. Such a community would be particularly beneficial for solo practitioners, lawyers in small firms and lawyers in rural communities and would also provide a con-venient way to connect with lawyers for referrals and recommendations, for spe-cialized expertise and to develop contacts in different geographic locations. Ten-tatively titled Gaggle on the Gavel is an attempt to create such a community that would gather a number of attractive features and functionality under one umbrella and be compliant with the rules of professional conduct with respect to client con-fidentiality, security, advertising and solicitation. A system has been designed, prototyped and revised based on feedback from a focus group of lawyers

Extension of the bayesian alphabet for genomic selection

<p>Abstract</p> <p>Background</p> <p>Two Bayesian methods, BayesC<it>π </it>and BayesD<it>π</it>, were developed for genomic prediction to address the drawback of BayesA and BayesB regarding the impact of prior hyperparameters and treat the prior probability <it>π </it>that a SNP has zero effect as unknown. The methods were compared in terms of inference of the number of QTL and accuracy of genomic estimated breeding values (GEBVs), using simulated scenarios and real data from North American Holstein bulls.</p> <p>Results</p> <p>Estimates of <it>π </it>from BayesC<it>π</it>, in contrast to BayesD<it>π</it>, were sensitive to the number of simulated QTL and training data size, and provide information about genetic architecture. Milk yield and fat yield have QTL with larger effects than protein yield and somatic cell score. The drawback of BayesA and BayesB did not impair the accuracy of GEBVs. Accuracies of alternative Bayesian methods were similar. BayesA was a good choice for GEBV with the real data. Computing time was shorter for BayesC<it>π </it>than for BayesD<it>π</it>, and longest for our implementation of BayesA.</p> <p>Conclusions</p> <p>Collectively, accounting for computing effort, uncertainty as to the number of QTL (which affects the GEBV accuracy of alternative methods), and fundamental interest in the number of QTL underlying quantitative traits, we believe that BayesC<it>π </it>has merit for routine applications.</p

‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological ‘gasotransmitter’, in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release. Here, we investigate the basis of its potent antibacterial activity against Escherichia coli and demonstrate, using three globin CO sensors, that CORM-2 releases negligible CO (<0.1 mol CO per mol CORM-2). A strong negative correlation between viability and cellular ruthenium accumulation implies that ruthenium toxicity underlies biocidal activity. Exogenous amino acids and thiols (especially cysteine, glutathione and N-acetyl cysteine) protected bacteria against inhibition of growth by CORM-2. Bacteria treated with 30 μM CORM-2, with added cysteine and histidine, exhibited no significant loss of viability, but were killed in the absence of these amino acids. Their prevention of toxicity correlates with their CORM-2-binding affinities (Cys, Kd 3 μM; His, Kd 130 μM) as determined by 1H-NMR. Glutathione is proposed to be an important intracellular target of CORM-2, with CORM-2 having a much higher affinity for reduced glutathione (GSH) than oxidised glutathione (GSSG) (GSH, Kd 2 μM; GSSG, Kd 25,000 μM). The toxicity of low, but potent, levels (15 μM) of CORM-2 was accompanied by cell lysis, as judged by the release of cytoplasmic ATP pools. The biological effects of CORM-2 and related CORMs, and the design of biological experiments, must be re-examined in the light of these data

Estimation and inference under economic restrictions

Estimation of economic relationships often requires imposition of constraints such as positivity or monotonicity on each observation. Methods to impose such constraints, however, vary depending upon the estimation technique employed. We describe a general methodology to impose (observation-specific) constraints for the class of linear regression estimators using a method known as constraint weighted bootstrapping. While this method has received attention in the nonparametric regression literature, we show how it can be applied for both parametric and nonparametric estimators. A benefit of this method is that imposing numerous constraints simultaneously can be performed seamlessly. We apply this method to Norwegian dairy farm data to estimate both unconstrained and constrained parametric and nonparametric models

Retaining young people in a longitudinal sexual health survey: a trial of strategies to maintain participation

&lt;p&gt;BACKGROUND:There is an increasing trend towards lower participation in questionnaire surveys. This reduces representativeness, increases costs and introduces particular challenges to longitudinal surveys, as researchers have to use complex statistical techniques which attempt to address attrition. This paper describes a trial of incentives to retain longitudinal survey cohorts from ages 16 to 20, to question them on the sensitive topic of sexual health.&lt;/p&gt; &lt;p&gt;METHODS: A longitudinal survey was conducted with 8,430 eligible pupils from two sequential year groups from 25 Scottish schools. Wave 1 (14 years) and Wave 2 (16 years) were conducted largely within schools. For Wave 3 (18 years), when everyone had left school, the sample was split into 4 groups that were balanced across predictors of survey participation: 1) no incentive; 2) chance of winning one of twenty-five vouchers worth 20 pounds; 3) chance of winning one 500 pounds voucher; 4) a definite reward of a 10 pounds voucher sent on receipt of their completed questionnaire. Outcomes were participation at Wave 3 and two years later at Wave 4. Analysis used logistic regression and adjusted for clustering at school level.&lt;/p&gt; &lt;p&gt;RESULTS: The only condition that had a significant and beneficial impact for pupils was to offer a definite reward for participation (Group 4). Forty-one percent of Group 4 participated in Wave 3 versus 27% or less for Groups 1 to 3. At Wave 4, 35% of Group 4 took part versus 25% or less for the other groups. Similarly, 22% of Group 4 participated in all four Waves of the longitudinal study, whereas for the other three groups it was 16% or less that participated in full.&lt;/p&gt; &lt;p&gt;CONCLUSIONS: The best strategy for retaining all groups of pupils and one that improved retention at both age 18 and age 20 was to offer a definite reward for participation. This is expensive, however, given the many benefits of retaining a longitudinal sample, we recommend inclusion of this as a research cost for cohort and other repeat-contact studies.&lt;/p&gt

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Inactivation of Poxviruses by Upper-Room UVC Light in a Simulated Hospital Room Environment

In the event of a smallpox outbreak due to bioterrorism, delays in vaccination programs may lead to significant secondary transmission. In the early phases of such an outbreak, transmission of smallpox will take place especially in locations where infected persons may congregate, such as hospital emergency rooms. Air disinfection using upper-room 254 nm (UVC) light can lower the airborne concentrations of infective viruses in the lower part of the room, and thereby control the spread of airborne infections among room occupants without exposing occupants to a significant amount of UVC. Using vaccinia virus aerosols as a surrogate for smallpox we report on the effectiveness of air disinfection, via upper-room UVC light, under simulated real world conditions including the effects of convection, mechanical mixing, temperature and relative humidity. In decay experiments, upper-room UVC fixtures used with mixing by a conventional ceiling fan produced decreases in airborne virus concentrations that would require additional ventilation of more than 87 air changes per hour. Under steady state conditions the effective air changes per hour associated with upper-room UVC ranged from 18 to 1000. The surprisingly high end of the observed range resulted from the extreme susceptibility of vaccinia virus to UVC at low relative humidity and use of 4 UVC fixtures in a small room with efficient air mixing. Increasing the number of UVC fixtures or mechanical ventilation rates resulted in greater fractional reduction in virus aerosol and UVC effectiveness was higher in winter compared to summer for each scenario tested. These data demonstrate that upper-room UVC has the potential to greatly reduce exposure to susceptible viral aerosols. The greater survival at baseline and greater UVC susceptibility of vaccinia under winter conditions suggest that while risk from an aerosol attack with smallpox would be greatest in winter, protective measures using UVC may also be most efficient at this time. These data may also be relevant to influenza, which also has improved aerosol survival at low RH and somewhat similar sensitivity to UVC