Projections of climate conditions that increase coral disease susceptibility and pathogen abundance and virulence

Rising sea temperatures are likely to increase the frequency of disease outbreaks affecting reef-building corals through impacts on coral hosts and pathogens. We present and compare climate model projections of temperature conditions that will increase coral susceptibility to disease, pathogen abundance and pathogen virulence. Both moderate (RCP 4.5) and fossil fuel aggressive (RCP 8.5) emissions scenarios are examined. We also compare projections for the onset of disease-conducive conditions and severe annual coral bleaching, and produce a disease risk summary that combines climate stress with stress caused by local human activities. There is great spatial variation in the projections, both among and within the major ocean basins, in conditions favouring disease development. Our results indicate that disease is as likely to cause coral mortality as bleaching in the coming decades. These projections identify priority locations to reduce stress caused by local human activities and test management interventions to reduce disease impacts

Cross-species protein sequence and gene structure prediction with fine-tuned Webscipio 2.0 and Scipio

<p>Abstract</p> <p>Background</p> <p>Obtaining transcripts of homologs of closely related organisms and retrieving the reconstructed exon-intron patterns of the genes is a very important process during the analysis of the evolution of a protein family and the comparative analysis of the exon-intron structure of a certain gene from different species. Due to the ever-increasing speed of genome sequencing, the gap to genome annotation is growing. Thus, tools for the correct prediction and reconstruction of genes in related organisms become more and more important. The tool Scipio, which can also be used via the graphical interface WebScipio, performs significant hit processing of the output of the Blat program to account for sequencing errors, missing sequence, and fragmented genome assemblies. However, Scipio has so far been limited to high sequence similarity and unable to reconstruct short exons.</p> <p>Results</p> <p>Scipio and WebScipio have fundamentally been extended to better reconstruct very short exons and intron splice sites and to be better suited for cross-species gene structure predictions. The Needleman-Wunsch algorithm has been implemented for the search for short parts of the query sequence that were not recognized by Blat. Those regions might either be short exons, divergent sequence at intron splice sites, or very divergent exons. We have shown the benefit and use of new parameters with several protein examples from completely different protein families in searches against species from several kingdoms of the eukaryotes. The performance of the new Scipio version has been tested in comparison with several similar tools.</p> <p>Conclusions</p> <p>With the new version of Scipio very short exons, terminal and internal, of even just one amino acid can correctly be reconstructed. Scipio is also able to correctly predict almost all genes in cross-species searches even if the ancestors of the species separated more than 100 Myr ago and if the protein sequence identity is below 80%. For our test cases Scipio outperforms all other software tested. WebScipio has been restructured and provides easy access to the genome assemblies of about 640 eukaryotic species. Scipio and WebScipio are freely accessible at <url>http://www.webscipio.org</url>.</p

Making Sense of Akrasia

There are two extreme poles in the literature on akrasia. Internalists hold that it's impossible to act intentionally against your better judgment, because there's a necessary internal relation between judgment and intentional action. To the contrary, externalists maintain that we can act intentionally against our better judgment, because the will operates independently of judgment. Critics of internalism argue that it fails a realism test—most people seem to think that we can and do act intentionally against our better judgment. And critics of externalism argue that it flirts with incoherence by severing the intimate link between judgment and action. Drawing on resources from phenomenology, the cognitive sciences, analytic action theory, and recent “hybrid models” of skilled action, I argue that one route beyond this theoretical impasse is to understand akrasia as a form of skillful pre-reflective intentional action. This strategy, I argue, preserves the internalist insight that there is indeed an intimate relation between judgment and intentional action; and it also confirms the externalist claim that this relation is defeasible, but it does so without falling into incoherence

Improved annotation with <i>de novo</i> transcriptome assembly in four social amoeba species

Background: Annotation of gene models and transcripts is a fundamental step in genome sequencing projects. Often this is performed with automated prediction pipelines, which can miss complex and atypical genes or transcripts. RNA sequencing (RNA-seq) data can aid the annotation with empirical data. Here we present de novo transcriptome assemblies generated from RNA-seq data in four Dictyostelid species: D. discoideum, P. pallidum, D. fasciculatum and D. lacteum. The assemblies were incorporated with existing gene models to determine corrections and improvement on a whole-genome scale. This is the first time this has been performed in these eukaryotic species. Results: An initial de novo transcriptome assembly was generated by Trinity for each species and then refined with Program to Assemble Spliced Alignments (PASA). The completeness and quality were assessed with the Benchmarking Universal Single-Copy Orthologs (BUSCO) and Transrate tools at each stage of the assemblies. The final datasets of 11,315-12,849 transcripts contained 5,610-7,712 updates and corrections to >50% of existing gene models including changes to hundreds or thousands of protein products. Putative novel genes are also identified and alternative splice isoforms were observed for the first time in P. pallidum, D. lacteum and D. fasciculatum. Conclusions: In taking a whole transcriptome approach to genome annotation with empirical data we have been able to enrich the annotations of four existing genome sequencing projects. In doing so we have identified updates to the majority of the gene annotations across all four species under study and found putative novel genes and transcripts which could be worthy for follow-up. The new transcriptome data we present here will be a valuable resource for genome curators in the Dictyostelia and we propose this effective methodology for use in other genome annotation projects

Identifying Alternative Hyper-Splicing Signatures in MG-Thymoma by Exon Arrays

BACKGROUND: The vast majority of human genes (>70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. METHODOLOGY/PRINCIPAL FINDINGS: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. CONCLUSIONS/SIGNIFICANCE: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatibility gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF(2) and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MG-thymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches