Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing

Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit

Coral Reefs at the Northernmost Tip of Borneo: An Assessment of Scleractinian Species Richness Patterns and Benthic Reef Assemblages.

The coral reefs at the northernmost tip of Sabah, Borneo will be established under a marine protected area: the Tun Mustapha Park (TMP) by the end of 2015. This area is a passage where the Sulu Sea meets the South China Sea and it is situated at the border of the area of maximum marine biodiversity, the Coral Triangle. The TMP includes fringing and patch reefs established on a relatively shallow sea floor. Surveys were carried out to examine features of the coral reefs in terms of scleractinian species richness, and benthic reef assemblages following the Reef Check substrate categories, with emphasis on hard coral cover. Variation in scleractinian diversity was based on the species composition of coral families Fungiidae (n = 39), Agariciidae (n = 30) and Euphylliidae (n = 15). The number of coral species was highest at reefs with a larger depth gradient i.e. at the periphery of the study area and in the deep South Banggi Channel. Average live hard coral cover across the sites was 49%. Only 7% of the examined reefs had > 75% hard coral cover, while the majority of the reef sites were rated fair (51%) and good (38%). Sites with low coral cover and high rubble fragments are evidence of blast fishing, although the observed damage appeared old. Depth was a dominant factor in influencing the coral species composition and benthic reef communities in the TMP. Besides filling in the information gaps regarding species richness and benthic cover for reef areas that were previously without any data, the results of this study together with information that is already available on the coral reefs of TMP will be used to make informed decisions on zoning plans for conservation priorities in the proposed park

Some remarks on computational approaches towards sustainable complex agri-food systems

International audienceAbstract Background Agri-food is one of the most important sectors of the industry in Europe and potentially a major contributor to the global warming. Sustainability issues in this context pose a huge challenge for several reasons: the variety of considered scales, the number of disciplines involved, the uncertainties, the out-of-equilibrium states, the complex quantitative and qualitative factors, the normative issues and the availability of data. Although important insight and breakthroughs have been attained in different scientific domains, an overarching and integrated analysis of these complex problems have yet to be realized. Scope and Approach This context creates huge opportunities for research in interaction with mathematical programming, integrative models and decision-support tools. The paper propose a computational viewpoint including questions of holistic approach, multiscale reconstruction and optimization. Some directions are discussed. Key Findings and Conclusions Several research questions based on a mathematical programming framework are emerging: how can such a framework manage uncertainty, cope with complex qualitative and quantitative information essential for social and environmental considerations, encompass diverse scales in space and time, cope with a multivariable dynamic environment and with scarcity of data. Moreover, how can it deal with different perspectives, types of models, research goals and data produced by conceptually disjoint scientific disciplines, ranging from physics and physiology to sociology and ethics? Building models is essential, but highly difficult; it will need a strong iterative interaction combining computational intensive methods, formal reasoning and the experts of the different fields. Some future research directions are proposed, involving all those dimensions: mathematical resilience, human-machine interactive learning and optimization techniques

The influence of depth and distance from the mainland on the benthic communities.

<p>The influence of depth and distance from the mainland on the benthic communities.</p

Overlay of the significant clusters from Fig 3 based on the SIMPROF analysis.

<p>Symbols in blue represent deep reef sites (> 20 m depth). Numbers indicate the total coral species for all three coral families. Sites with ≥ 45 species are shown in red bold font. Wind rose showing dominant wind directions is based on observations between January 2012 and November 2013 obtained from the Kudat Airport, Sabah from <a href="http://windfinder.com/" target="_blank">windfinder.com</a>.</p

The influence of depth, exposure and distance from the mainland on the coral species richness in the TMP.

<p>The influence of depth, exposure and distance from the mainland on the coral species richness in the TMP.</p

The occurrence of common and uncommon coral species in the proposed Tun Mustapha Park.

<p>The occurrence of common and uncommon coral species in the proposed Tun Mustapha Park.</p

Research area at the northern tip of Borneo.

<p>Symbols for data collected at survey sites; green: coral species richness only; blue: benthic community only: black: both. The sites indicated by the black symbol were plotted according to GPS coordinates of the coral species richness surveys (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146006#pone.0146006.s010" target="_blank">S1 Table</a>). Labels (locality names excluding the proposed Tun Mustapha Park boundary) are given according to British Admiralty Nautical Charts no. 948 and 1654. Selat Banggi Selatan (South Banggi Channel) is indicated by the dashed grey line.</p

Species richness accumulation curves (observed and estimated).

<p>(A) Fungiidae at 47 sites, (B) Agariciidae and (C) Euphylliidae, each at 35 sites.</p

Group-averaged hierarchical clustering dendrogram of coral composition based on the Bray-Curtis similarity index.

<p>Coral species composition was based on 35 sites where data was collected for all three coral families. Four significant clusters and one outlier (indicated by the symbols) were computed by the similarity profile (SIMPROF) analysis.</p