Past Japanese successes show the way to accomplish future goals

Many parasitic diseases have been eradicated in industrialized countries and well-proven tools and techniques exist to control them. However, the same diseases still cause incalculable ill health and suffering in the developing world. The difficulty remains how best to apply existing solutions where they are most needed. Within a period of 25 years following World War II, Japan eliminated many parasitic diseases and raised national health and living standards to world-leading levels. Gradually, the predominantly community-driven and intersectoral collaborative partnership systems (i.e. private sector, public sector, general public, etc.) and practices that worked in Japan are being extended to Asia and now Africa. These are backed by the provision of substantial human and financial resources from a nation whose population retains the reputation as being the healthiest and longest living in the world.     

Metabolomics standards initiative: ontology working group work in progress

In this article we present the activities of the Ontology Working Group (OWG) under the Metabolomics Standards Initiative (MSI) umbrella. Our endeavour aims to synergise the work of several communities, where independent activities are underway to develop terminologies and databases for metabolomics investigations. We have joined forces to rise to the challenges associated with interpreting and integrating experimental process and data across disparate sources (software and databases, private and public). Our focus is to support the activities of the other MSI working groups by developing a common semantic framework to enable metabolomics-user communities to consistently annotate the experimental process and to enable meaningful exchange of datasets. Our work is accessible via a public webpage and a draft ontology has been posted under the Open Biological Ontology umbrella. At the very outset, we have agreed to minimize duplications across omics domains through extensive liaisons with other communities under the OBO Foundry. This is work in progress and we welcome new participants willing to volunteer their time and expertise to this open effort. See the MSI Ontology Working Group website for a complete list of members and contributors. Web URL:     

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background

Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15.

Methods and Findings

Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0–2 years and BMI from 2–10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0–2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5–10), and were largely mediated by fat mass at age 15.

Conclusion

Changes in PI/BMI from 0–10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5–10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.     

Identification of a specific isoform of tomato lipoxygenase (TomloxC) involved in the generation of fatty acid-derived flavor compounds

There are at least five lipoxygenases (TomloxA, TomloxB, TomloxC, TomloxD, and TomloxE) present in tomato (Lycopersicon esculentum Mill.) fruit, but their role in generation of fruit flavor volatiles has been unclear. To assess the physiological role of TomloxC in the generation of volatile C6 aldehyde and alcohol flavor compounds, we produced transgenic tomato plants with greatly reduced TomloxC using sense and antisense constructs under control of the cauliflower mosaic virus 35S promoter. The expression level of the TomloxC mRNA in some transgenic plants was selectively reduced by gene silencing or antisense inhibition to between 1% and 5% of the wild-type controls, but the expression levels of mRNAs for the four other isoforms were unaffected. The specific depletion of TomloxC in transgenic tomatoes led to a marked reduction in the levels of known flavor volatiles, including hexanal, hexenal, and hexenol, to as little as 1.5% of those of wild-type controls following maceration of ripening fruit. Addition of linoleic or linolenic acid to fruit homogenates significantly increased the levels of flavor volatiles, but the increase with the TomloxC-depleted transgenic fruit extracts was much lower than with the wild-type control. Confocal imaging of tobacco (Nicotiana tabacum) leaf cells expressing a TomloxC-GFP fusion confirmed a chloroplast localization of the protein. Together, these results suggest that TomloxC is a chloroplast-targeted lipoxygenase isoform that can use both linoleic and linolenic acids as substrates to generate volatile C6 flavor compounds. The roles of the other lipoxygenase isoforms are discussed.     

CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitation

Ca2+-dependent facilitation (CDF) of voltage-gated calcium current is a powerful mechanism for up-regulation of Ca2+ influx during repeated membrane depolarization. CDF of L-type Ca2+ channels (Ca(v)1.2) contributes to the positive force-frequency effect in the heart and is believed to involve the activation of Ca2+/calmodulin-dependent kinase II (CaMKII). How CaMKII is activated and what its substrates are have not yet been determined. We show that the pore-forming subunit alpha(1C) (Ca(v)alpha1.2) is a CaMKII substrate and that CaMKII interaction with the COOH terminus of alpha1C is essential for CDF of L-type channels. Ca2+ influx triggers distinct features of CaMKII targeting and activity. After Ca2+-induced targeting to alpha1C, CaMKII becomes tightly tethered to the channel, even after calcium returns to normal levels. In contrast, activity of the tethered CaMKII remains fully Ca2+/CaM dependent, explaining its ability to operate as a calcium spike frequency detector. These findings clarify the molecular basis of CDF and demonstrate a novel enzymatic mechanism by which ion channel gating can be modulated by activity.     

Prevalence of agglutinating antibodies to Sarcocystis neurona in skunks (Mephitis Mephitis), raccoons (Procyon lotor), and opossums (Didelphis Virginiana) from Connecticut

Equine protozoal myeloencephalitis is the most important protozoan disease of horses in North America and is usually caused by Sarcocystis neurona. Natural cases of encephalitis caused by S. neurona have been reported in skunks (Mephitis mephitis) and raccoons (Procyon lotor). Opossums (Didelphis spp.) are the only known definitive host. Sera from 24 striped skunks, 12 raccoons, and 7 opossums (D. virginiana) from Connecticut were examined for agglutinating antibodies to S. neurona using the S. neurona agglutination test (SAT) employing formalin-fixed merozoites as antigen. The SAT was validated for skunk sera using pre- and postinfection serum samples from 2 experimentally infected skunks. Of the 24 (46%) skunks 11 were positive, and all 12 raccoons were positive for S. neurona antibodies. None of the 7 opossums was positive for antibodies to S. neurona. These results suggest that exposure to sporocysts of S. neurona by intermediate hosts is high in Connecticut. The absence of antibodies in opossums collected from the same areas is most likely because of the absence of systemic infection in the definitive host.     

Is Cassava the Answer to African Climate Change Adaptation?

This paper examines the impacts of climate change on cassava production in Africa, and questions whether cassava can play an important role in climate change adaptation. First, we examine the impacts that climate change will likely have on cassava itself, and on other important staple food crops for Africa including maize, millets, sorghum, banana, and beans based on projections to 2030. Results indicate that cassava is actually positively impacted in many areas of Africa, with ?3.7% to +17.5% changes in climate suitability across the continent. Conversely, for other major food staples, we found that they are all projected to experience negative impacts, with the greatest impacts for beans (?16%?±?8.8), potato (?14.7?±?8.2), banana (?2.5%?±?4.9), and sorghum (?2.66%?±?6.45). We then examined the likely challenges that cassava will face from pests and diseases through the use of ecological niche modeling for cassava mosaic disease, whitefly, brown streak disease and cassava mealybug. The findings show that the geographic distribution of these pests and diseases are projected to change, with both new areas opening up and areas where the pests and diseases are likely to leave or reduce in pressure. We finish the paper by looking at the abiotic traits of priority for crop adaptation for a 2030 world, showing that greater drought tolerance could bring some benefits in all areas of Africa, and that cold tolerance in Southern Africa will continue to be a constraint for cassava despite a warmer 2030 world, hence breeding needs to keep a focus on this trait. Importantly, heat tolerance was not found to be a major priority for crop improvement in cassava in the whole of Africa, but only in localized pockets of West Africa and the Sahel. The paper concludes that cassava is potentially highly resilient to future climatic changes and could provide Africa with options for adaptation whilst other major food staples face challenges.     

Isolation of Pandemic Vibrio parahaemolyticus from UK Water and Shellfish Produce

Vibrio parahaemolyticus is a Gram-negative, halophilic bacterium found commonly in temperate and warm estuarine waters worldwide. V. parahaemolyticus is considered an emerging bacterial pathogen in Europe and has been responsible for several recent seafood-associated outbreaks. During ad hoc testing of raw shellfish produce in May 2012, pandemic group (O3:K6) V. parahaemolyticus was isolated from Pacific oysters (Crassostrea gigas), harvested in Southern England. Follow-on testing of water and shellfish, encompassing a small number geographically diverse sites, also retrieved pandemic group isolates. These strains are amongst the most northerly pandemic strains described to date and represent the first instance of pandemic V. parahaemolyticus isolated in the UK, highlighting the expanding geographical distribution of these foodborne pathogens in the environment.     

Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines

Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational analysis provided valuable insight into the origins of the observed activity profiles.