SHARDS: Constraints on the dust attenuation law of star-forming galaxies at z~2

We make use of SHARDS, an ultra-deep (<26.5AB) galaxy survey that provides optical photo-spectra at resolution R~50, via medium band filters (FWHM~150A). This dataset is combined with ancillary optical and NIR fluxes to constrain the dust attenuation law in the rest-frame NUV region of star-forming galaxies within the redshift window 1.5<z<3. We focus on the NUV bump strength (B) and the total-to-selective extinction ratio (Rv), targeting a sample of 1,753 galaxies. By comparing the data with a set of population synthesis models coupled to a parametric dust attenuation law, we constrain Rv and B, as well as the colour excess, E(B-V). We find a correlation between Rv and B, that can be interpreted either as a result of the grain size distribution, or a variation of the dust geometry among galaxies. According to the former, small dust grains are associated with a stronger NUV bump. The latter would lead to a range of clumpiness in the distribution of dust within the interstellar medium of star-forming galaxies. The observed wide range of NUV bump strengths can lead to a systematic in the interpretation of the UV slope ($\beta$) typically used to characterize the dust content. In this study we quantify these variations, concluding that the effects are $\Delta\beta$~0.4.Comment: 13 pages, 11+2 figures, 3 tables. MNRAS, in pres

Coding potential of the products of alternative splicing in human

Background: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. Results: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. Conclusions: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity

High-Throughput Proteomics Detection of Novel Splice Isoforms in Human Platelets

Alternative splicing (AS) is an intrinsic regulatory mechanism of all metazoans. Recent findings suggest that 100% of multiexonic human genes give rise to splice isoforms. AS can be specific to tissue type, environment or developmentally regulated. Splice variants have also been implicated in various diseases including cancer. Detection of these variants will enhance our understanding of the complexity of the human genome and provide disease-specific and prognostic biomarkers. We adopted a proteomics approach to identify exon skip events - the most common form of AS. We constructed a database harboring the peptide sequences derived from all hypothetical exon skip junctions in the human genome. Searching tandem mass spectrometry (MS/MS) data against the database allows the detection of exon skip events, directly at the protein level. Here we describe the application of this approach to human platelets, including the mRNA-based verification of novel splice isoforms of ITGA2, NPEPPS and FH. This methodology is applicable to all new or existing MS/MS datasets

Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx

Background: Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction. Results: We generate the first annotated draft of the Iberian lynx genome and carry out genome-based analyses of lynx demography, evolution, and population genetics. We identify a series of severe population bottlenecks in the history of the Iberian lynx that predate its known demographic decline during the 20th century and have greatly impacted its genome evolution. We observe drastically reduced rates of weak-to-strong substitutions associated with GC-biased gene conversion and increased rates of fixation of transposable elements. We also find multiple signatures of genetic erosion in the two remnant Iberian lynx populations, including a high frequency of potentially deleterious variants and substitutions, as well as the lowest genome-wide genetic diversity reported so far in any species. Conclusions: The genomic features observed in the Iberian lynx genome may hamper short- and long-term viability through reduced fitness and adaptive potential. The knowledge and resources developed in this study will boost the research on felid evolution and conservation genomics and will benefit the ongoing conservation and management of this emblematic species

How organic farmers view their own practice: results from the Czech Republic

This paper addresses the development of organic agriculture in the Czech Republic, which is seen as a success story among post-communist countries. The relatively short history of organic farming and specific contextual factors raises questions about the nature and meaning of Czech organic farming. The goal of this study was to find out how farmers view their own practice, interpret its symbolic value, and construct its content. This empirical study uses Q methodology aimed at the identification of the collectively-shared perspectives belonging engaged actors. Data were gathered through semi-standardized interviews with Czech farmers registered in official organic scheme. The analysis emphasized three components, which are considered as three distinct perspectives possessed by organic farmers; that is, (1) organic farming as a way of life, (2) as an occupation, and (3) as a production of food of an alternative quality compared to conventional food. Each viewpoint entails a different understanding of what organic farming means; each then—when considered together—comprises the meaning of organic agriculture in the Czech Republic. The presented classification of the farmers holding the viewpoints contributes to the ongoing theoretical discussion regarding the nature of the current organic sector, its development and potential conventionalization

Measuring Global Credibility with Application to Local Sequence Alignment

Computational biology is replete with high-dimensional (high-D) discrete prediction and inference problems, including sequence alignment, RNA structure prediction, phylogenetic inference, motif finding, prediction of pathways, and model selection problems in statistical genetics. Even though prediction and inference in these settings are uncertain, little attention has been focused on the development of global measures of uncertainty. Regardless of the procedure employed to produce a prediction, when a procedure delivers a single answer, that answer is a point estimate selected from the solution ensemble, the set of all possible solutions. For high-D discrete space, these ensembles are immense, and thus there is considerable uncertainty. We recommend the use of Bayesian credibility limits to describe this uncertainty, where a (1−α)%, 0≤α≤1, credibility limit is the minimum Hamming distance radius of a hyper-sphere containing (1−α)% of the posterior distribution. Because sequence alignment is arguably the most extensively used procedure in computational biology, we employ it here to make these general concepts more concrete. The maximum similarity estimator (i.e., the alignment that maximizes the likelihood) and the centroid estimator (i.e., the alignment that minimizes the mean Hamming distance from the posterior weighted ensemble of alignments) are used to demonstrate the application of Bayesian credibility limits to alignment estimators. Application of Bayesian credibility limits to the alignment of 20 human/rodent orthologous sequence pairs and 125 orthologous sequence pairs from six Shewanella species shows that credibility limits of the alignments of promoter sequences of these species vary widely, and that centroid alignments dependably have tighter credibility limits than traditional maximum similarity alignments

Allelic Gene Structure Variations in Anopheles gambiae Mosquitoes

Allelic gene structure variations and alternative splicing are responsible for transcript structure variations. More than 75% of human genes have structural isoforms of transcripts, but to date few studies have been conducted to verify the alternative splicing systematically.The present study used expressed sequence tags (ESTs) and EST tagged SNP patterns to examine the transcript structure variations resulting from allelic gene structure variations in the major human malaria vector, Anopheles gambiae. About 80% of 236,004 available A. gambiae ESTs were successfully aligned to A. gambiae reference genomes. More than 2,340 transcript structure variation events were detected. Because the current A. gambiae annotation is incomplete, we re-annotated the A. gambiae genome with an A. gambiae-specific gene model so that the effect of variations on gene coding could be better evaluated. A total of 15,962 genes were predicted. Among them, 3,873 were novel genes and 12,089 were previously identified genes. The gene completion rate improved from 60% to 84%. Based on EST support, 82.5% of gene structures were predicted correctly. In light of the new annotation, we found that approximately 78% of transcript structure variations were located within the coding sequence (CDS) regions, and >65% of variations in the CDS regions have the same open-reading-frame. The association between transcript structure isoforms and SNPs indicated that more than 28% of transcript structure variation events were contributed by different gene alleles in A. gambiae.We successfully expanded the A. gambiae genome annotation. We predicted and analyzed transcript structure variations in A. gambiae and found that allelic gene structure variation plays a major role in transcript diversity in this important human malaria vector

Entropy Measures Quantify Global Splicing Disorders in Cancer

Most mammalian genes are able to express several splice variants in a phenomenon known as alternative splicing. Serious alterations of alternative splicing occur in cancer tissues, leading to expression of multiple aberrant splice forms. Most studies of alternative splicing defects have focused on the identification of cancer-specific splice variants as potential therapeutic targets. Here, we examine instead the bulk of non-specific transcript isoforms and analyze their level of disorder using a measure of uncertainty called Shannon's entropy. We compare isoform expression entropy in normal and cancer tissues from the same anatomical site for different classes of transcript variations: alternative splicing, polyadenylation, and transcription initiation. Whereas alternative initiation and polyadenylation show no significant gain or loss of entropy between normal and cancer tissues, alternative splicing shows highly significant entropy gains for 13 of the 27 cancers studied. This entropy gain is characterized by a flattening in the expression profile of normal isoforms and is correlated to the level of estimated cellular proliferation in the cancer tissue. Interestingly, the genes that present the highest entropy gain are enriched in splicing factors. We provide here the first quantitative estimate of splicing disruption in cancer. The expression of normal splice variants is widely and significantly disrupted in at least half of the cancers studied. We postulate that such splicing disorders may develop in part from splicing alteration in key splice factors, which in turn significantly impact multiple target genes