ALBERT

Description: With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner. However, obtaining a complete catalog of cancer genes is difficult due to the heterogeneous molecular nature of the disease and the limitations of available computational methods. Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. We provide a list of 291 high-confidence cancer driver genes acting on 3,205 tumors from 12 different cancer types. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumor type. The novel driver candidates complement our current picture of the emergence of these diseases. In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis. Scientific Reports 3 doi: 10.1038/srep02650

Description: Psoriasis is a common chronic inflammatory disease of the skin. We sought to use bacterial community abundance data to assess the feasibility of developing multivariate molecular signatures for differentiation of cutaneous psoriatic lesions, clinically unaffected contralateral skin from psoriatic patients, and similar cutaneous loci in matched healthy control subjects. Using 16S rRNA high-throughput DNA sequencing, we assayed the cutaneous microbiome for 51 such matched specimen triplets including subjects of both genders, different age groups, ethnicities and multiple body sites. None of the subjects had recently received relevant treatments or antibiotics. We found that molecular signatures for the diagnosis of psoriasis result in significant accuracy ranging from 0.75 to 0.89 AUC, depending on the classification task. We also found a significant effect of DNA sequencing and downstream analysis protocols on the accuracy of molecular signatures. Our results demonstrate that it is feasible to develop accurate molecular signatures for the diagnosis of psoriasis from microbiomic data. Scientific Reports 3 doi: 10.1038/srep02620

Description: Among the genotoxic halofuranones formed by chlorination in water are mucochloric acid (MCA, 3,4-dichloro-5-hydroxyfuran-2(5 H )-one) and mucobromic acid (MBA, 3,4-dibromo-5-hydroxyfuran-2(5 H )-one). These acids are direct genotoxins and potential carcinogens, with the capacity to alkylate the DNA bases. In recent years, they have also attracted attention in the synthesis of furanone derivatives. Mucohalic acids (MXA) exist in solution as an equilibrium between three species; a cyclic lactone-lactol , an open-chain aldehyde-acid , and the dissociated form of the latter . The distribution of the three species in the equilibrium has synthetic, toxicological, and environmental implications owing to their different functionalization. The case of the neutral open-chain form is of special interest, since it is expected to be highly reactive. We have experimentally determined the apparent dissociation constant of the cyclic species . Their values suggest that at neutral pH MXA are mostly present as the dissociated carboxylate-aldehyde. The dissociation constant of the open-chain neutral species and the cyclization equilibrium constant were determined in water and organic solvents, using density functional theory and ab initio methods. The results suggest that the undissociated aldehyde is a minor species at any given pH. The structure of MXA in solution and the influence of the level of theory on the calculated geometry are discussed. Copyright © 2011 John Wiley & Sons, Ltd. Mucohalic acids exist in solution as an equilibrium between three species; a cyclic lactone-lactol, an open-chain aldehyde-acid, and the dissociated form of the later. The distribution of the three species in equilibrium has synthetic, toxicological, and environmental implications and thus, we have determined by a combined experimental and computational approach, the respective equilibrium constants.

Description: This study focuses on storm deposits in the Muschelkalk facies of the Betic Cordillera (southern Spain) and interprets their deposition mechanisms. Three types of storm deposit are distinguished: (i) pot/gutter casts; (ii) tempestite beds; and (iii) storm-winnowed deposits. Each deposit provides information about the carbonate platform environment in which it was deposited. The tempestite models proposed are: (i) the bypass-zone tempestite model, occurring in a muddy ramp at the epicontinental basin margin. This model is characterized by potholes and gutters that form in a shoreline bypass-zone during storms; (ii) the gradient-current tempestite model in which frequent tempestite beds are related to storm gradient currents. Thickness and grain size decrease towards the deep distal ramp; and (iii) the winnowed deposit tempestite model whereby storm deposits are winnowed and deposited in the same environment with only short lateral transport having occurred. This model evokes more restricted and shallower conditions, lagoons or inland seas. The distribution of all these deposits in the stratigraphic sections studied corroborate the eustatic third-order cycle identified, although the different features of the storm deposits and their positions in each section indicate a subsidence varying in time and space. In the transgressive stage, the margins of the epicontinental basin were a well-developed ramp with potholes and gutters. In contrast, during the high sea-level stage, storm deposits generated tempestite beds or storm-winnowed deposits in the different areas. The epicontinental carbonate platform with ramp edges evolved into a complex depositional system of coastal and shallow-marine environments with lagoons and restricted inland seas. Thus, the epicontinental platform underwent substantial change from the Late Anisian to the Late Ladinian and this is reflected in its storm deposits.

Description: Microscale electrokinetic techniques have great potential for the separation and sorting of microorganisms, and could solve the need for rapid and early detection of pathogens in medical diagnostics and food safety applications. Presented here is the application of micro particle image velocimetry for the characterization of electrokinetic transport of three types of microorganisms: Escherichia coli, Ankistrodesmus spiralis , and Saccharomyces cerevisiae . The electrokinetic behavior of these microorganisms was characterized employing a straight glass microchannel and direct current electric fields (50–300 V cm –1 ). The effects of the type and size of microorganism, electric field magnitude, and suspending medium characteristics were analyzed. Additionally, electrokinetic differentiation was achieved when a sample containing a mixture of the three types of microorganisms was analyzed by generating an electropherogram in one minute, identifying that three different species were present. These results demonstrate that fast and effective detection, and differentiation of intact microorganisms can be achieved employing microscale electrokinetic techniques. Characterization of electrokinetic transport of three types of microorganisms: Escherichia coli, Ankistrodesmus spiralis , and Saccharomyces cerevisiae employing particle image velocimetry. Electrokinetic detection and differentiation were achieved by generating an electropherogram in one minute, identifying that three different species were present.

Description: Scientific Reports 3 doi: 10.1038/srep02952

Description: The importance of parasitism for host populations depends on local parasite richness and prevalence: usually host individuals face higher infection risk in areas where parasites are most diverse, and host dispersal to or from these areas may have fitness consequences. Knowing how parasites are and will be distributed in space and time (in a context of global change) is thus crucial from both an ecological and a biological conservation perspective. Nevertheless, most research articles focus just on elaborating models of parasite distribution instead of parasite diversity. We produced distribution models of the areas where haemosporidian parasites are currently highly diverse (both at community and within-host levels) and prevalent among Iberian populations of a model passerine host: the blackcap Sylvia atricapilla ; and how these areas are expected to vary according to three scenarios of climate change. Based on these models, we analysed whether variation among populations in parasite richness or prevalence are expected to remain the same or change in the future, thereby reshuffling the geographic mosaic of host-parasite interactions as we observe it today. Our models predict a rearrangement of areas of high prevalence and richness of parasites in the future, with Haemoproteus and Leucocytozoon parasites (today the most diverse genera in blackcaps) losing areas of high diversity and Plasmodium parasites (the most virulent ones) gaining them. Likewise, the prevalence of multiple infections and parasite infracommunity richness would be reduced. Importantly, differences among populations in the prevalence and richness of parasites are expected to decrease in the future, creating a more homogeneous parasitic landscape. This predicts an altered geographic mosaic of host-parasite relationships, which will modify the interaction arena in which parasite virulence evolves. This article is protected by copyright. All rights reserved.

Description: Question How reliable is the process of delimiting plant species by morphotyping sterile specimens from a highly diverse Amazonian forest plot? Location Biological Dynamics of Forest Fragments Project (BDFFP), Central Amazon, Manaus, Brazil. Methods A taxonomic exercise was conducted during a Center for Tropical Forest Science (CTFS) Taxonomy Workshop held in Manaus in April 2011, using specimens collected in a 25-ha forest plot. The plant species from this plot had been previously delimited by morphotyping of ca. 80 000 sterile specimens, a process that resulted in the recognition of 115 cases (accounting for 38% of all trees) in which species delimitation was problematic. For the workshop, we selected a subsample of specimens for eight of these difficult cases (taxonomic groups/complexes) and asked 14 participants with different levels of botanical training to independently sort these specimens into morphospecies. We then compared the classifications made by all participants and explored correlations between botanical training and plant classification. Results The classification of specimens into morphospecies was highly variable among participants, except for one taxonomic group/complex, for which the median pair-wise similarity was 95%. For the other seven taxonomic groups/complexes, median pair-wise similarity values ranged from 52% to 67%. Training did not increase the similarity in the definition of morphospecies except for two taxonomic groups/complexes, for which there was higher congruence between the classifications made by participants with a high level of botanical training than in comparisons that included less-experienced participants. The total number of morphospecies defined by participants was highly variable for all taxonomic groups/complexes, with the total number varying from 12 to 46 (a 383% difference). Conclusions Local plant species delimitation by morphotyping sterile specimens is prone to large uncertainties, and botanical training may not reduce them. We argue that uncertainty in species delimitation should be explicitly considered in plant biodiversity inventories as diversity estimates may be strongly affected by such uncertainties. We recommend that species delimitation and identification be treated as separate processes and that difficulties be explicitly recorded, so as to permit error estimates and the refinement of taxonomic data. Poor taxonomic knowledge, lack of tools and high diversity limit our ability to recognize plant species in Amazon forest plot inventories. While the identification of species is a well-known problem, the delimitation of local species is considered unproblematic. We show that local species delimitation is also prone to large uncertainties, and that botanical experience may not reduce them.

Description: Understanding how environmental variation influences the distribution of parasite diversity is critical if we are to anticipate disease emergence risks associated with global change. However, choosing the relevant variables for modelling current and future parasite distributions may be difficult: candidate predictors are many, and they seldom are statistically independent. This problem often leads to simplistic models of current and projected future parasite distributions, with climatic variables prioritized over potentially important landscape features or host population attributes. We studied avian blood parasites of the genera Plasmodium , Haemoproteus and Leucocytozoon (which are viewed as potential emergent pathogens) in 37 Iberian blackcap Sylvia atricapilla populations. We used Partial Least Squares regression to assess the relative importance of a wide array of putative determinants of variation in the diversity of these parasites, including climate, landscape features and host population migration. Both prevalence and richness of parasites were predominantly related to climate (an effect which was primarily, but not exclusively driven by variation in temperature), but landscape features and host migration also explained variation in parasite diversity. Remarkably, different models emerged for each parasite genus, although all parasites were studied in the same host species. Our results show that parasite distribution models, which are usually based on climatic variables alone, improve by including other types of predictors. Moreover, closely related parasites may show different relationships to the same environmental influences (both in magnitude and direction). Thus a model used to develop one parasite distribution can probably not be applied identically even to the most similar host-parasite systems. This article is protected by copyright. All rights reserved.