An essential saccharide binding domain for the mAb 2C7 established for Neisseria gonorrhoeae LOS by ES-MS and MSn

A study of bacterial surface oligosaccharides were investigated among different strains of Neisseria gonorrhoeae to correlate structural features essential for binding to the MAb 2C7. This epitope is widely expressed and conserved in gonococcal isolates, characteristics essential to an effective candidate vaccine antigen. Sample lipooligosaccharides (LOS), was prepared by a modification of the hot phenol-water method from which de-O-acetylated LOS and oligosaccharide (OS) components were analyzed by ES-MS-CID-MS and ES-MSnin a triple quadrupole and an ion trap mass spectrometer, respectively. Previously documented natural heterogeneity was apparent from both LOS and OS preparations which was admixed with fragments induced by hydrazine and mild acid treatment. Natural heterogeneity was limited to phosphorylation and antenni extensions to the alpha-chain. Mild acid hydrolysis to release OS also hydrolyzed the beta(1-->6) glycosidic linkage of lipid A. OS structures were determined by collisional and resonance excitation combined with MS and multistep MSn which provided sequence information from both neutral loss, and nonreducing terminal fragments. A comparison of OS structures, with earlier knowledge of MAb binding, enzyme treatment, and partial acid hydrolysis indicates a generic overlapping domain for 2C7 binding. Reoccurring structural features include a Hepalpha(1-->3)Hepbeta(1-->5)KDO trisaccharide core branched on the nonreducing terminus (Hep-2) with an alpha(1-->2) linked GlcNAc (gamma-chain), and an alpha-linked lactose (beta-chain) residue. From the central heptose (Hep-1), a beta(1-->4) linked lactose (alpha-chain), moiety is required although extensions to this residue appear unnecessary.      

Nutrient requirements of exotic tree species in Zimbabwe

Pot and field experiments were conducted in the greenhouse and at three field sites (Marondera, Domboshawa and Makoholi) in Zimbabwe to examine the effects of soils and fertilizers on nutrient uptake and growth of 6 exotic tree species (Eucalyptus camaldulensis, E. grandis, E. tereticornis, Leucaena leucocephala, Casuarina cunninghamiana, and Acacia holosericea). Plant growth, N and P contents of all species were increased by the application of N, P, K and micronutrient fertilizers. The effect of individual nutrients (N, P, K and micronutrients) and their combination on Eucalyptus species was further investigated in a pot experiment using soil from Domboshawa. Eucalyptus species responded only to N application and no significant interactions were found between N and the other elements. Nutrient uptake results showed that E. camaldulensis and E. tereticornis removed more cations than the N-fixing trees but only in the fertilized treatments. L. leucocephala and C. cunninghamiana were higher in P, but no clear trends were observed for N. Plant growth and nutrient uptake by E. camaldulensis. C. cunninghamiana and A. holosericea were assessed in the field at the three sites. Plant species grown in the Marondera site had greater height and diameter at breast height (DBH) than those in the two other sites. These results followed trends in soil nutrient contents. The analysis of foliage revealed differences in the nutrient concentration of leaves from different trees, but no effect of site was found. The interrelationships between plant characteristics, soil and foliage nutrients were examined. In a pot experiment, mineral N was the only variable correlated with growth response and nutrient uptake, while in the field the only significant correlation was obtained with soil pH.     

Intrinsic Protein Fluorescence Interferes with Detection of Tear Glycoproteins in SDS-Polyacrylamide Gels Using Extrinsic Fluorescent Dyes

Intrinsic protein fluorescence may interfere with the visualization of proteins after SDS-polyacrylamide electrophoresis. In an attempt to analyze tear glycoproteins in gels, we ran tear samples and stained the proteins with a glycoprotein-specific fluorescent dye. The fluorescence detected was not limited to glycoproteins. There was strong intrinsic fluorescence of proteins normally found in tears after soaking the gels in 40% methanol plus 1-10% acetic acid and, to a lesser extent, in methanol or acetic acid alone. Nanograms of proteins gave visible native fluorescence and interfere with extrinsic fluorescent dye detection. Poly-L-lysine, which does not contain intrinsically fluorescent amino acids, did not fluoresce.     

Improving wood quality in the western gulf forest tree improvement program: the problem of multiple breeding objectives

Currently, both industrial and private landowners in the Western Gulf Forest Tree Improvement Program (WGFTIP) area are compensated for their timber primarily based on the weight or volume of green wood reaching the mill gate. This places an immediate economic focus on adaptability and volume growth. However, selection for volume growth alone could result in decreased wood quality over time. Wood quality characteristics including stem straightness, wood specific gravity, and microfibril angle have either neutral or slightly unfavorable genetic correlations with volume growth in the WGFTIP loblolly pine (Pinus taeda L.) program. Since most WGFTIP members also consider wood quality an important selection criterion, the WGFTIP must define the best possible set of selection criteria given that (1) no single set of breeding objectives can be considered optimal for multiple products and (2) improvement in wood quality has no readily recognized economic importance in the existing market. To meet this challenge, the WGFTIP has implemented different strategies for its mainline breeding and deployment populations. In the mainline population, consistent breeding and selection criteria are used across members, while in the various deployment populations, selections are tailored to meet the specific needs of each member. The WGFTIP is also developing an elite wood quality population (WQEPop) based on backward selection. For the WQEPop to be successful, the economic importance of improved wood quality must be recognized, and landowners must be compensated for growing higher quality timber, especially if this results in reduced volume production. Improved methodology for within-family selection and for wood quality trait measurement is also important.     

The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data

Background

Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP''s clinical efficacy.

Methods and Findings

A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox''s regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan–Meier survival estimates were 97.7% (95% CI 97.3%–98.1%) at day 42 and 97.2% (95% CI 96.7%–97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3–2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%–96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%–21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed.

Conclusions

DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation. Please see later in the article for the Editors'' Summary     

Stimulation of the autonomic nervous system in colorectal surgery: a study protocol for a randomized controlled trial

In this study we describe the sociodemographic characteristics of people participating in a clinical trial on the safety and immunogenicity of a H5N1 influenza vaccine and we identify the main motivations for joining it.     

Individual variation evades the Prisoner's Dilemma

Background  

The Prisoner's Dilemma (PD) is a widely used paradigm to study cooperation in evolutionary biology, as well as in fields as diverse as moral philosophy, sociology, economics and politics. Players are typically assumed to have fixed payoffs for adopting certain strategies, which depend only on the strategy played by the opponent. However, fixed payoffs are not realistic in nature. Utility functions and the associated payoffs from pursuing certain strategies vary among members of a population with numerous factors. In biology such factors include size, age, social status and expected life span; in economics they include socio-economic status, personal preference and past experience; and in politics they include ideology, political interests and public support. Thus, no outcome is identical for any two different players.