194 research outputs found
"Grant us eyes, grant us eyes! Plant eyes on our brains, to cleanse our beastly idiocy!": FromSoftware's Bloodborne, and the New Frontier of the Gothic
This article will consider the ways that Bloodborne (FromSoftware, 2015) plays on a broad range of Gothic themes and conventions, utilising unusual narrative techniques and gameplay mechanics which offer the player a means by which they might experience a Gothic narrative in ways that the traditional novel format does not allow for. It will argue that Bloodborne showcases the genre's potential new frontier: converting conventions into interesting new gameplay mechanics, and letting the player experience the genre through player-led narrative and agency
GenomeRNAi: a database for cell-based RNAi phenotypes. 2009 update
The GenomeRNAi database (http://www.genomernai.org/) contains phenotypes from published cell-based RNA interference (RNAi) screens in Drosophila and Homo sapiens. The database connects observed phenotypes with annotations of targeted genes and information about the RNAi reagent used for the perturbation experiment. The availability of phenotypes from Drosophila and human screens also allows for phenotype searches across species. Besides reporting quantitative data from genome-scale screens, the new release of GenomeRNAi also enables reporting of data from microscopy experiments and curated phenotypes from published screens. In addition, the database provides an updated resource of RNAi reagents and their predicted quality that are available for the Drosophila and the human genome. The new version also facilitates the integration with other genomic data sets and contains expression profiling (RNA-Seq) data for several cell lines commonly used in RNAi experiments
Pan-parastagonospora comparative genome analysis-effector prediction and genome evolution
We report a fungal pan-genome study involving Parastagonospora spp., including 21 isolates of the wheat (Triticum aestivum) pathogen Parastagonospora nodorum, 10 of the grass-infecting Parastagonospora avenae, and 2 of a closely related undefined sister species. We observed substantial variation in the distribution of polymorphisms across the pan-genome, including repeat-induced point mutations, diversifying selection and gene gains and losses.We also discovered chromosome-scale inter and intraspecific presence/absence variation of some sequences, suggesting the occurrence of one or more accessory chromosomes or regions that may play a role in host-pathogen interactions. The presence of known pathogenicity effector loci SnToxA, SnTox1, and SnTox3 varied substantially among isolates. Three P. nodorum isolates lacked functional versions for all three loci, whereas three P. avenae isolates carried one or both of the SnTox1 and SnTox3 genes, indicating previously unrecognized potential for discovering additional effectors in the P. nodorum-wheat pathosystem. We utilized the pangenomic comparative analysis to improve the prediction of pathogenicity effector candidates, recovering the three confirmed effectors among our top-ranked candidates. We propose applying this pan-genomic approach to identify the effector repertoire involved in other host-microbe interactions involving necrotrophic pathogens in the Pezizomycotina
Integrating splice-isoform expression into genome-scale models characterizes breast cancer metabolism
Motivation: Despite being often perceived as the main contributors to cell
fate and physiology, genes alone cannot predict cellular phenotype. During the
process of gene expression, 95% of human genes can code for multiple proteins
due to alternative splicing. While most splice variants of a gene carry the
same function, variants within some key genes can have remarkably different
roles. To bridge the gap between genotype and phenotype, condition- and
tissue-specific models of metabolism have been constructed. However, current
metabolic models only include information at the gene level. Consequently, as
recently acknowledged by the scientific community, common situations where
changes in splice-isoform expression levels alter the metabolic outcome cannot
be modeled. Results: We here propose GEMsplice, the first method for the
incorporation of splice-isoform expression data into genome-scale metabolic
models. Using GEMsplice, we make full use of RNA-Seq quantitative expression
profiles to predict, for the first time, the effects of splice isoform-level
changes in the metabolism of 1455 patients with 31 different breast cancer
types. We validate GEMsplice by generating cancer-versus-normal predictions on
metabolic pathways, and by comparing with gene-level approaches and available
literature on pathways affected by breast cancer. GEMsplice is freely available
for academic use at https://github.com/GEMsplice/GEMsplice_code. Compared to
state-of-the-art methods, we anticipate that GEMsplice will enable for the
first time computational analyses at transcript level with splice-isoform
resolution
A genotypic analysis of five P. aeruginosa strains after biofilm infection by phages targeting different cell surface receptors
The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb. 2017.01229/full#supplementary-materialAntibiotic resistance constitutes one of the most serious threats to the global public health and urgently requires new and effective solutions. Bacteriophages are bacterial viruses increasingly recognized as being good alternatives to traditional antibiotic therapies. In this study, the efficacy of phages, targeting different cell receptors, against Pseudomonas aeruginosa PAO1 biofilm and planktonic cell cultures was evaluated over the course of 48h. Although significant reductions in the number of viable cells were achieved for both cases, the high level of adaptability of the bacteria in response to the selective pressure caused by phage treatment resulted in the emergence of phage-resistant variants. To further investigate the genetic makeup of phage-resistant variants isolated from biofilm infection experiments, some of these bacteria were selected for phenotypic and genotypic characterization. Whole genome sequencing was performed on five phage-resistant variants and all of them carried mutations affecting the galU gene as well as one of pil genes. The sequencing analysis further revealed that three of the P. aeruginosa PAO1 variants carry large deletions (> 200 kbp) in their genomes. Complementation of the galU mutants with wild-type galU in trans restored LPS expression on the bacterial cell surface of these bacterial strains and rendered the complemented strains to be sensitive to phages. This provides unequivocal evidence that inactivation of galU function was associated with resistance to the phages that uses LPS as primary receptors. Overall, this work demonstrates that P. aeruginosa biofilms can survive phage attack and develop phage-resistant variants exhibiting defective LPS production and loss of type IV pili that are well adapted to the biofilm mode of growth.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the project PTDC/BBB-BSS/6471/2014; the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER006684) and BioTecNorte operation (NORTE-01-0145-FEDER000004)funded by European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. SS is an FCT investigator (IF/01413/2013). Work done in the lab of JL is supported by Canadian Institutes of Health Research (Grant MOP-14687). YH was a recipient of a postdoctoral fellowship award from Cystic Fibrosis, and JL holds a Canada Research Chair in Cystic Fibrosis and Microbial Glycobiology funded by the Canadian Foundation of Innovation. Work done in the lab of CK is supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada(#371639).info:eu-repo/semantics/publishedVersio
Abundant toxin-related genes in the genomes of beneficial symbionts from deep-sea hydrothermal vent mussels
Bathymodiolus mussels live in symbiosis with intracellular sulfur-oxidizing (SOX) bacteria that provide them with nutrition. We sequenced the SOX symbiont genomes from two Bathymodiolus species. Comparison of these symbiont genomes with those of their closest relatives revealed that the symbionts have undergone genome rearrangements, and up to 35% of their genes may have been acquired by horizontal gene transfer. Many of the genes specific to the symbionts were homologs of virulence genes. We discovered an abundant and diverse array of genes similar to insecticidal toxins of nematode and aphid symbionts, and toxins of pathogens such as Yersinia and Vibrio. Transcriptomics and proteomics revealed that the SOX symbionts express the toxin-related genes (TRGs) in their hosts. We hypothesize that the symbionts use these TRGs in beneficial interactions with their host, including protection against parasites. This would explain why a mutualistic symbiont would contain such a remarkable 'arsenal' of TRG
Infection Strategies Deployed by Botrytis cinerea, Fusarium acuminatum, and Rhizopus stolonifer as a Function of Tomato Fruit Ripening Stage
Worldwide, 20–25% of all harvested fruit and vegetables are lost annually in the field
and throughout the postharvest supply chain due to rotting by fungal pathogens.
Most postharvest pathogens exhibit necrotrophic or saprotrophic lifestyles, resulting in
decomposition of the host tissues and loss of marketable commodities. Necrotrophic
fungi can readily infect ripe fruit leading to the rapid establishment of disease symptoms.
However, these pathogens generally fail to infect unripe fruit or remain quiescent until
host conditions stimulate a successful infection. Previous research on infections of
fruit has mainly been focused on the host’s genetic and physicochemical factors that
inhibit or promote disease. Here, we investigated if fruit pathogens can modify their own
infection strategies in response to the ripening stage of the host. To test this hypothesis,
we profiled global gene expression of three fungal pathogens that display necrotrophic
behavior—Botrytis cinerea, Fusarium acuminatum, and Rhizopus stolonifer—during
interactions with unripe and ripe tomato fruit. We assembled and functionally annotated
the transcriptomes of F. acuminatum and R. stolonifer as no genomic resources
were available. Then, we conducted differential gene expression analysis to compare
each pathogen during inoculations versus in vitro conditions. Through characterizing
patterns of overrepresented pathogenicity and virulence functions (e.g., phytotoxin
production, cell wall degradation, and proteolysis) among the differentially expressed
genes, we were able to determine shared strategies among the three fungi during
infections of compatible (ripe) and incompatible (unripe) fruit tissues. Though each
pathogen’s strategy differed in the details, interactions with unripe fruit were commonly
characterized by an emphasis on the degradation of cell wall components, particularly
pectin, while colonization of ripe fruit featured more heavily redox processes, proteolysis,
metabolism of simple sugars, and chitin biosynthesis. Furthermore, we determined that
the three fungi were unable to infect fruit from the non-ripening (nor) tomato mutant, confirming that to cause disease, these pathogens require the host tissues to undergo
specific ripening processes. By enabling a better understanding of fungal necrotrophic
infection strategies, we move closer to generating accurate models of fruit diseases and
the development of early detection tools and effective management strategies
Population Differences in Transcript-Regulator Expression Quantitative Trait Loci
Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1×10−6 revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1×10−7) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis
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