Molecular mechanism of decision-making in glycosaminoglycan biosynthesis

Two major glycosaminoglycan types, heparan sulfate (HS) and chondroitin sulfate (CS), control many aspects of development and physiology in a type-specific manner. HS and CS are attached to core proteins via a common linker tetrasaccharide, but differ in their polymer backbones. How core proteins are specifically modified with HS or CS has been an enduring mystery. By reconstituting glycosaminoglycan biosynthesis in vitro, we establish that the CS-initiating N-acetylgalactosaminyltransferase CSGALNACT2 modifies all glycopeptide substrates equally, whereas the HS-initiating N-acetylglucosaminyltransferase EXTL3 is selective. Structure-function analysis reveals that acidic residues in the glycopeptide substrate and a basic exosite in EXTL3 are critical for specifying HS biosynthesis. Linker phosphorylation by the xylose kinase FAM20B accelerates linker synthesis and initiation of both HS and CS, but has no effect on the subsequent polymerisation of the backbone. Our results demonstrate that modification with CS occurs by default and must be overridden by EXTL3 to produce HS

Obesity is associated with impaired immune response to influenza vaccination in humans

Background:Obesity is an independent risk factor for morbidity and mortality from pandemic influenza H1N1. Influenza is a significant public health threat, killing an estimated 250 000–500 000 people worldwide each year. More than one in ten of the world's adult population is obese and more than two-thirds of the US adult population is overweight or obese. No studies have compared humoral or cellular immune responses to influenza vaccination in healthy weight, overweight and obese populations despite clear public health importance.Objective:The study employed a convenience sample to determine the antibody response to the 2009–2010 inactivated trivalent influenza vaccine (TIV) in healthy weight, overweight and obese participants at 1 and 12 months post vaccination. In addition, activation of CD8+ T cells and expression of interferon-γ and granzyme B were measured in influenza-stimulated peripheral blood mononuclear cell (PBMC) cultures.Results:Body mass index (BMI) correlated positively with higher initial fold increase in IgG antibodies detected by enzyme-linked immunosorbent assay to TIV, confirmed by HAI antibody in a subset study. However, 12 months post vaccination, higher BMI was associated with a greater decline in influenza antibody titers. PBMCs challenged ex vivo with vaccine strain virus, demonstrated that obese individuals had decreased CD8+ T-cell activation and decreased expression of functional proteins compared with healthy weight individuals.Conclusion:These results suggest obesity may impair the ability to mount a protective immune response to influenza virus

Surveillance of antenatal influenza vaccination: validity of current systems and recommendations for improvement

Abstract Background: Although influenza vaccination is recommended during pregnancy as standard of care, limited surveillance data are available for monitoring uptake. Our aim was to evaluate the validity of existing surveillance in Western Australia for measuring antenatal influenza immunisations. Methods: The self-reported vaccination status of 563 women who delivered between April and October 2013 was compared against three passive data collection sources: a state-wide antenatal influenza vaccination database maintained by the Department of Health, a public maternity hospital database, and a private health service database. Sensitivity, specificity, and positive and negative predictive values were calculated for each system using self-report as the “gold standard.” Results: The state-wide antenatal vaccination database detected 45.7 % (95 % CI: 40.1–51.4 %) of influenza vaccinations, the public maternity hospital database detected 66.7 % (95 % CI: 55.1–76.9 %), and the private health service database detected 29.1 % (95 % CI: 20.5–39.4 %). Specificity exceeded 90 % and positive predictive values exceeded 80 % for each system. Sensitivity was lowest for women whose antenatal care was provided by a private obstetrician. Conclusions: Existing resources for surveillance of antenatal influenza vaccinations detect 29–67 % of vaccinations. Considering the importance of influenza immunisation as a public health intervention, particularly in pregnant women, improvements to routine monitoring of influenza vaccination is warranted

Nutrition rehabilitation of undernourished children utilizing Spiruline and Misola

BACKGROUND: Malnutrition constitutes a public health problem throughout the world and particularly in developing countries. AIMS: The objective of the study is to assess the impact of an elementary integrator composed of Spiruline (Spirulina platensis) and Misola (millet, soja, peanut) produced at the Centre Medical St Camille (CMSC) of Ouagadougou, Burkina Faso, on the nutritional status of undernourished children. MATERIALS AND METHODS: 550 undernourished children of less than 5 years old were enrolled in this study, 455 showed severe marasma, 57 marasma of medium severity and 38 kwashiorkor plus marasma. We divided the children randomly into four groups: 170 were given Misola (731 ± 7 kcal/day), 170 were given Spiruline plus traditional meals (748 ± 6 kcal/day), 170 were given Spiruline plus Misola (767 ± 5 kcal/day). Forty children received only traditional meals (722 ± 8 kcal/day) and functioned as the control group. The duration of this study was eight weeks. RESULTS AND DISCUSSION: Anthropometrics and haematological parameters allowed us to appreciate both the nutritional and biological evolution of these children. The rehabilitation with Spiruline plus Misola (this association gave an energy intake of 767 ± 5 kcal/day with a protein assumption of 33.3 ± 1.2 g a day), both greater than Misola or Spiruline alone, seems to correct weight loss more quickly. CONCLUSION: Our results indicate that Misola, Spiruline plus traditional meals or Spiruline plus Misola are all a good food supplement for undernourished children, but the rehabilitation by Spiruline plus Misola seems synergically favour the nutrition rehabilitation better than the simple addition of protein and energy intake

CheS-Mapper - Chemical Space Mapping and Visualization in 3D

Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis

Inter-layer Adhesion Performance of Steel Packaging Materials for Food Cans Under Retort Conditions

The steel packaging industry faces the dual challenge imposed by legislation to eradicate the use of Chrome(VI) from sub- strate manufacture and the removal of Bisphenol-A (BPA) from the organic lacquer at the point of food contact. The paper reports on an experimental investigation into the quality of adhesion between the coatings and substrates as a result of the retort process, typically the harshest conditions to which the materials will be exposed. In terms of adhesion, the novel Chrome(III) substrates show promise when compared with current Chrome(VI) substrate. There is a significant reduction in the adhesion of the polyester-based Bisphenol-A non-intent lacquers compared to the incumbent epoxy-phenolic lacquers. Adhesion performance is lower with an increase in retort temperature and time of exposure. The adhesion further reduces in mild acidic and saline conditions. The reduction in adhesion post-retort is attributed to the sensitivity of the polyester-based BPANI lacquers to water vapour absorption. The process reversible nature of the adhesion loss indicates that, at short time- scales, the adhesion loss is a result of polyester hydrolysis. Acidic and saline solutions also lead to a reduction in adhesion as a result of metal surface corrosion. The paper has impact on producers, fillers and consumers of steel packaging foodstuff

A general modeling and visualization tool for comparing different members of a group: application to studying tau-mediated regulation of microtubule dynamics

<p>Abstract</p> <p>Background</p> <p>Innumerable biological investigations require comparing collections of molecules, cells or organisms to one another with respect to one or more of their properties. Almost all of these comparisons are performed manually, which can be susceptible to inadvertent bias as well as miss subtle effects. The development and application of computer-assisted analytical and interpretive tools could help address these issues and thereby dramatically improve these investigations.</p> <p>Results</p> <p>We have developed novel computer-assisted analytical and interpretive tools and applied them to recent studies examining the ability of 3-repeat and 4-repeat tau to regulate the dynamic behavior of microtubules in vitro. More specifically, we have developed an automated and objective method to define growth, shortening and attenuation events from real time videos of dynamic microtubules, and demonstrated its validity by comparing it to manually assessed data. Additionally, we have used the same data to develop a general strategy of building different models of interest, computing appropriate dissimilarity functions to compare them, and embedding them on a two-dimensional plot for visualization and easy comparison. Application of these methods to assess microtubule growth rates and growth rate distributions established the validity of the embedding procedure and revealed non-linearity in the relationship between the tau:tubulin molar ratio and growth rate distribution.</p> <p>Conclusion</p> <p>This work addresses the need of the biological community for rigorously quantitative and generally applicable computational tools for comparative studies. The two-dimensional embedding method retains the inherent structure of the data, and yet markedly simplifies comparison between models and parameters of different samples. Most notably, even in cases where numerous parameters exist by which to compare the different samples, our embedding procedure provides a generally applicable computational strategy to detect subtle relationships between different molecules or conditions that might otherwise escape manual analyses.</p

A highly efficient multi-core algorithm for clustering extremely large datasets

<p>Abstract</p> <p>Background</p> <p>In recent years, the demand for computational power in computational biology has increased due to rapidly growing data sets from microarray and other high-throughput technologies. This demand is likely to increase. Standard algorithms for analyzing data, such as cluster algorithms, need to be parallelized for fast processing. Unfortunately, most approaches for parallelizing algorithms largely rely on network communication protocols connecting and requiring multiple computers. One answer to this problem is to utilize the intrinsic capabilities in current multi-core hardware to distribute the tasks among the different cores of one computer.</p> <p>Results</p> <p>We introduce a multi-core parallelization of the k-means and k-modes cluster algorithms based on the design principles of transactional memory for clustering gene expression microarray type data and categorial SNP data. Our new shared memory parallel algorithms show to be highly efficient. We demonstrate their computational power and show their utility in cluster stability and sensitivity analysis employing repeated runs with slightly changed parameters. Computation speed of our Java based algorithm was increased by a factor of 10 for large data sets while preserving computational accuracy compared to single-core implementations and a recently published network based parallelization.</p> <p>Conclusions</p> <p>Most desktop computers and even notebooks provide at least dual-core processors. Our multi-core algorithms show that using modern algorithmic concepts, parallelization makes it possible to perform even such laborious tasks as cluster sensitivity and cluster number estimation on the laboratory computer.</p