Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans

Tsetse flies are the principal insect vectors of African trypanosomes—sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African trypanosomiasis. Precise details of the life cycle have yet to be established, but the parasite life cycle involves crossing the insect peritrophic matrix (PM). The PM consists of the polysaccharide chitin, several hundred proteins, and both glycosamino- and galactosaminoglycan (GAG) polysaccharides. Owing to the technical challenges of detecting small amounts of GAG polysaccharides, their conclusive identification and composition have not been possible until now. Following removal of PMs from the insects and the application of heparinases (bacterial lyase enzymes that are specific for heparan sulphate (HS) GAG polysaccharides), dot blots with a HS-specific antibody showed heparan sulphate proteoglycans (HSPGs) to be present, consistent with Glossina morsitans morsitans genome analysis, as well as the likely expression of the HSPGs syndecan and perlecan. Exhaustive HS digestion with heparinases, fluorescent labeling of the resulting disaccharides with BODIPY fluorophore, and separation by strong anion exchange chromatography then demonstrated the presence of HS for the first time and provided the disaccharide composition. There were no significant differences in the type of disaccharide species present between genders or between ages (24 vs. 48 h post emergence), although the HS from female flies was more heavily sulphated overall. Significant differences, which may relate to differences in infection between genders or ages, were evident, however, in overall levels of 2-O-sulphation between sexes and, for females, between 24 and 48 h post-emergence, implying a change in expression or activity for the 2-O-sulphotransferase enzyme. The presence of significant quantities of disaccharides containing the monosaccharide GlcNAc6S contrasts with previous findings in Drosophila melanogaster and suggests subtle differences in HS fine structure between species of the Diptera

Creating User-Friendly Tools for Data Analysis and Visualization in K-12 Classrooms: A Fortran Dinosaur Meets Generation Y

During the summer of 2007, as part of the second year of a NASA-funded project in partnership with Christopher Newport University called SPHERE (Students as Professionals Helping Educators Research the Earth), a group of undergraduate students spent 8 weeks in a research internship at or near NASA Langley Research Center. Three students from this group formed the Clouds group along with a NASA mentor (Chambers), and the brief addition of a local high school student fulfilling a mentorship requirement. The Clouds group was given the task of exploring and analyzing ground-based cloud observations obtained by K-12 students as part of the Students' Cloud Observations On-Line (S'COOL) Project, and the corresponding satellite data. This project began in 1997. The primary analysis tools developed for it were in FORTRAN, a computer language none of the students were familiar with. While they persevered through computer challenges and picky syntax, it eventually became obvious that this was not the most fruitful approach for a project aimed at motivating K-12 students to do their own data analysis. Thus, about halfway through the summer the group shifted its focus to more modern data analysis and visualization tools, namely spreadsheets and Google(tm) Earth. The result of their efforts, so far, is two different Excel spreadsheets and a Google(tm) Earth file. The spreadsheets are set up to allow participating classrooms to paste in a particular dataset of interest, using the standard S'COOL format, and easily perform a variety of analyses and comparisons of the ground cloud observation reports and their correspondence with the satellite data. This includes summarizing cloud occurrence and cloud cover statistics, and comparing cloud cover measurements from the two points of view. A visual classification tool is also provided to compare the cloud levels reported from the two viewpoints. This provides a statistical counterpart to the existing S'COOL data visualization tool, which is used for individual ground-to-satellite correspondences. The Google(tm) Earth file contains a set of placemarks and ground overlays to show participating students the area around their school that the satellite is measuring. This approach will be automated and made interactive by the S'COOL database expert and will also be used to help refine the latitude/longitude location of the participating schools. Once complete, these new data analysis tools will be posted on the S'COOL website for use by the project participants in schools around the US and the world

Minimising medicine use in organic dairy herds through animal health and welfare planning

Livestock is important in many organic farming systems, and it is an explicit goal to ensure high levels of animal health and welfare (AHW) through good management. This will lead to reduced medicine use and better quality of animal products. In two EU network projects NAHWOA & SAFO it was concluded that this is not guaranteed merely by following organic standards. Both networks recommended implementation of individual animal health plans to stimulate organic farmers to improve AHW. These plans should include a systematic evaluation of AHW and be implemented through dialogue with each farmer in order to identify goals and plan improvements. 15 research institutions in 8 European countries are involved in the proposed project with the main objective to minimise medicine use in organic dairy herds through active and well planned AHW promotion and disease prevention. The project consists of 5 work packages, 4 of which comprise research activities building on current research projects, new applications across borders, exchange of knowledge, results and conclusions between participating countries, and adopting them to widely different contexts. International and national workshops facilitate this exchange. Focus areas are animal health planning, AHW assessment using animal based parameters and development of advisory systems and farmer groups. Epidemiological analyses of the effect on AHW from reduced medicine use and herd improvements are planned in all participating countries

CEO pay, shareholder returns, and accounting profits

We assess the impact on CEO pay (including salary, cash bonus, and benefits in kind) of changes in both accounting and shareholder returns in 99 British companies in the years 1972-89. After correcting for heterogeneity biases inherent in the standard specifications of the problem, we find a strong positive relationship between CEO pay and within-company changes in shareholder returns, and no statistically significant relationship between CEO pay and within-company changes in accounting returns. Differences between firms in long-term average profitability do appear to have a substantial effect on CEO pay, while differences between firms in shareholder returns add nothing to the within-firm pay dynamics.These findings call into question the rationale for explicitly share-based incentive schemes

Ethical issues in implementation research: a discussion of the problems in achieving informed consent

Background: Improved quality of care is a policy objective of health care systems around the world. Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice, and hence to reduce inappropriate care. It includes the study of influences on healthcare professionals' behaviour and methods to enable them to use research findings more effectively. Cluster randomized trials represent the optimal design for evaluating the effectiveness of implementation strategies. Various codes of medical ethics, such as the Nuremberg Code and the Declaration of Helsinki inform medical research, but their relevance to cluster randomised trials in implementation research is unclear. This paper discusses the applicability of various ethical codes to obtaining consent in cluster trials in implementation research. Discussion: The appropriate application of biomedical codes to implementation research is not obvious. Discussion of the nature and practice of informed consent in implementation research cluster trials must consider the levels at which consent can be sought, and for what purpose it can be sought. The level at which an intervention is delivered can render the idea of patient level consent meaningless. Careful consideration of the ownership of information, and rights of access to and exploitation of data is required. For health care professionals and organizations, there is a balance between clinical freedom and responsibility to participate in research. Summary: While ethical justification for clinical trials relies heavily on individual consent, for implementation research aspects of distributive justice, economics, and political philosophy underlie the debate. Societies may need to trade off decisions on the choice between individualized consent and valid implementation research. We suggest that social sciences codes could usefully inform the consideration of implementation research by members of Research Ethics Committees

Malaria during pregnancy and foetal haematological status in Blantyre, Malawi

Background: Although maternal anaemia often stems from malaria infection during pregnancy, its effects on foetal haemoglobin levels are not straightforward. Lower-than-expected cord haemoglobin values in malarious versus non-malarious regions were noted by one review, which hypothesized they resulted from foetal immune activation to maternal malaria. This study addressed this idea by examining cord haemoglobin levels in relation to maternal malaria, anaemia, and markers of foetal immune activation. Methods: Cord haemoglobin levels were examined in 32 malaria-infected and 58 uninfected women in Blantyre, Malawi, in relation to maternal haemoglobin levels, malaria status, and markers of foetal haematological status, hypoxia, and inflammation, including TNF-alpha, TGF-beta, and ferritin. All women were HIV-negative. Results: Although malaria was associated with a reduction in maternal haemoglobin (10.8 g/dL vs. 12.1 g/ dL, p < 0.001), no reduction in cord haemoglobin and no significant relationship between maternal and cord haemoglobin levels were found. Cord blood markers of haematological and hypoxic statuses did not differ between malaria-infected and uninfected women. Maternal malaria was associated with decreased TGF- and increased cord ferritin, the latter of which was positively correlated with parasitaemia (r = 0.474, p = 0.009). Increased cord ferritin was associated with significantly decreased birth weight and gestational length, although maternal and cord haemoglobin levels and malaria status had no effect on birth outcome. Conclusion: In this population, cord haemoglobin levels were protected from the effect of maternal malaria. However, decreased TGF- and elevated ferritin levels in cord blood suggest foetal immune activation to maternal malaria, which may help explain poor birth outcomes

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Chandra X-Ray Observations of Two Unusual BAL Quasars

We report sensitive Chandra X-ray non-detections of two unusual, luminous Iron Low-Ionization Broad Absorption Line Quasars (FeLoBALs). The observations do detect a non-BAL, wide-binary companion quasar to one of the FeLoBAL quasars. We combine X-ray-derived column density lower limits (assuming solar metallicity) with column densities measured from ultraviolet spectra and CLOUDY photoionization simulations to explore whether constant density slabs at broad line region densities can match the physical parameters of these two BAL outflows, and find that they cannot. In the "overlapping-trough" object SDSS J0300+0048, we measure the column density of the X-ray absorbing gas to be N_H >= 1.8 x 1024 cm-2. From the presence of Fe II UV78 absorption but lack of Fe II UV195/UV196 absorption, we infer the density in that part of the absorbing region to be n_e ~ 106 cm-3. We do find that a slab of gas at that density might be able to explain this object's absorption. In the Fe III-dominant object SDSS J2215-0045, the X-ray absorbing column density of N_H >= 3.4 x 1024 cm-2 is consistent with the Fe III-derived N_H >= 2 x 1022 cm-2 provided the ionization parameter is log U > 1.0 for both the n_e = 1011 cm-3 and n_e = 1012 cm-3 scenarios considered (such densities are required to produce Fe III absorption without Fe II absorption). However, the velocity width of the absorption rules out its being concentrated in a single slab at these densities. Instead, this object's spectrum can be explained by a low density, high ionization and high temperature disk wind that encounters and ablates higher density, lower ionization Fe III-emitting clumps.Comment: 18 pages, 6 figure

A universal model for mobility and migration patterns

Introduced in its contemporary form by George Kingsley Zipf in 1946, but with roots that go back to the work of Gaspard Monge in the 18th century, the gravity law is the prevailing framework to predict population movement, cargo shipping volume, inter-city phone calls, as well as bilateral trade flows between nations. Despite its widespread use, it relies on adjustable parameters that vary from region to region and suffers from known analytic inconsistencies. Here we introduce a stochastic process capturing local mobility decisions that helps us analytically derive commuting and mobility fluxes that require as input only information on the population distribution. The resulting radiation model predicts mobility patterns in good agreement with mobility and transport patterns observed in a wide range of phenomena, from long-term migration patterns to communication volume between different regions. Given its parameter-free nature, the model can be applied in areas where we lack previous mobility measurements, significantly improving the predictive accuracy of most of phenomena affected by mobility and transport processes.Comment: Main text and supplementary informatio