The origins of the classic European wine grapes (Vitis vinifera) have been the subject of much speculation. In a search for parental relationships, microsatellite loci were analyzed in more than 300 grape cultivars. Sixteen wine grapes that have long been grown in northeastern France, including 'Chardonnay', 'Gamay noir', 'Aligoté', and 'Melon', have microsatellite genotypes consistent with their being the progeny of a single pair of parents, 'Pinot' and 'Gouais blanc', both of which were widespread in this region in the Middle Ages. Parentage analysis at 32 microsatellite loci provides statistical support for these relationships.
BackgroundAllergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power.ResultsWe have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization.ConclusionsA gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.
A prerequisite for successful screening campaigns in drug discovery or chemical genetics is the availability of structurally and thus functionally diverse compound libraries. Diversity-oriented synthesis (DOS) provides strategies for the generation of such libraries, of which the build/couple/pair (B/C/P) algorithm is the most frequently used. We have developed an advanced B/C/P strategy that incorporates multidimensional coupling. In this approach, structural diversity is not only defined by the nature of the building blocks employed, but also by the linking motif installed during the coupling reaction. We applied this step-efficient approach in a DOS of a library that consisted of 73 macrocyclic compounds based around 59 discrete scaffolds. The macrocycles prepared cover a broad range of different molecular shapes, as illustrated by principal moment-of-inertia analysis. This demonstrates the capability of the advanced B/C/P strategy using multidimensional coupling for the preparation of structurally diverse compound collections.
The formation process(es) responsible for creating the observed geologically recent gully features on Mars has remained the subject of intense debate since their discovery. We present new data and analysis of northern hemisphere gullies from Mars Global Surveyor data which is used to test the various proposed mechanisms of gully formation. We located 137 Mars Orbiter Camera (MOC) images in the northern hemisphere that contain clear evidence of gully landforms and analyzed these images in combination with Mars Orbiter Laser Altimeter (MOLA) and Thermal Emission Spectrometer (TES) data to provide quantitative measurements of numerous gully characteristics. Parameters we measured include apparent source depth and distribution, vertical and horizontal dimensions, slopes, orientations, and present-day characteristics that affect local ground temperatures. Northern hemisphere gullies are clustered in Arcadia Planitia, Tempe Terra, Acidalia Planitia, and Utopia Planitia. These gullies form in craters (84%), knobby terrain (4%), valleys (3%), other/unknown terrains (9%) and are found on all slope orientations although the majority of gullies are equator-facing. Most gullies (63%) are associated with competent rock strata, 26% are not associated with strata, and 11% are ambiguous. Assuming thermal conductivities derived from TES measurements as well as modeled surface temperatures, we find that 95% of the gully alcove bases with adequate data coverage lie at depths where subsurface temperatures are greater than 273 K and 5% of the alcove bases lie within the solid water regime. The average alcove length is 470 m and the average channel length is 690 m. Based on a comparison of measured gully features with predictions from the various models of gully formation, we find that models involving carbon dioxide, melting ground ice in the upper few meters of the soil, dry landslide, and surface snowmelt are the least likely to describe the formation of the martian gullies. Although some discrepancies still exist between prediction and observation, the shallow and deep aquifer models remain as the most plausible theories. Interior processes involving subsurface fluid sources are generally favored over exogenic processes such as wind and snowfall for explaining the origin of the martian gullies. These findings gleaned from the northern hemisphere data are in general agreement with analyses of gullies in the southern hemisphere [Heldmann, J.L., Mellon, M.T., 2004. Icarus 168, 285-304]. Published by Elsevier Inc.
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