116,036 research outputs found

    Phenotypic microarrays suggest Escherichia coli ST131 is not a metabolically distinct lineage of extra-intestinal pathogenic E. coli

    Get PDF
    Extraintestinal pathogenic E. coli (ExPEC) are the major aetiological agent of urinary tract infections (UTIs) in humans. The emergence of the CTX-M producing clone E. coli ST131 represents a major challenge to public health worldwide. A recent study on the metabolic potential of E. coli isolates demonstrated an association between the E. coli ST131 clone and enhanced utilisation of a panel of metabolic substrates. The studies presented here investigated the metabolic potential of ST131 and other major ExPEC ST isolates using 120 API test reagents and found that ST131 isolates demonstrated a lower metabolic activity for 5 of 120 biochemical tests in comparison to non-ST131 ExPEC isolates. Furthermore, comparative phenotypic microarray analysis showed a lack of specific metabolic profile for ST131 isolates countering the suggestion that these bacteria are metabolically fitter and therefore more successful human pathogens

    JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma.

    Get PDF
    A prominent mechanism of acquired resistance to BRAF inhibitors in BRAF (V600) -mutant melanoma is associated with the upregulation of receptor tyrosine kinases. Evidences suggested that this resistance mechanism is part of a more complex cellular adaptation process. Using an integrative strategy, we found this mechanism to invoke extensive transcriptomic, (phospho-) proteomic and phenotypic alterations that accompany a cellular transition to a de-differentiated, mesenchymal and invasive state. Even short-term BRAF-inhibitor exposure leads to an early adaptive, differentiation state change-characterized by a slow-cycling, persistent state. The early persistent state is distinct from the late proliferative, resistant state. However, both differentiation states share common signaling alterations including JUN upregulation. Motivated by the similarities, we found that co-targeting of BRAF and JUN is synergistic in killing fully resistant cells; and when used up-front, co-targeting substantially impairs the formation of the persistent subpopulation. We confirmed that JUN upregulation is a common response to BRAF inhibitor treatment in clinically treated patient tumors. Our findings demonstrate that events shared between early- and late-adaptation states provide candidate up-front co-treatment targets

    An integrated genomic approach for the study of mandibular prognathism in the European seabass (Dicentrarchus labrax)

    Get PDF
    Skeletal anomalies in farmed fish are a relevant issue affecting animal welfare and health and causing significant economic losses. Here, a high-density genetic map of European seabass for QTL mapping of jaw deformity was constructed and a genome-wide association study (GWAS) was carried out on a total of 298 juveniles, 148 of which belonged to four full-sib families. Out of 298 fish, 107 were affected by mandibular prognathism (MP). Three significant QTLs and two candidate SNPs associated with MP were identified. The two GWAS candidate markers were located on ChrX and Chr17, both in close proximity with the peaks of the two most significant QTLs. Notably, the SNP marker on Chr17 was positioned within the Sobp gene coding region, which plays a pivotal role in craniofacial development. The analysis of differentially expressed genes in jaw-deformed animals highlighted the "nervous system development" as a crucial pathway in MP. In particular, Zic2, a key gene for craniofacial morphogenesis in model species, was significantly down-regulated in MP-affected animals. Gene expression data revealed also a significant down-regulation of Sobp in deformed larvae. Our analyses, integrating transcriptomic and GWA methods, provide evidence for putative mechanisms underlying seabass jaw deformity

    (Re)-conciliation of genetics and genomics approaches for cotton fiber quality improvement

    Full text link
    The integration of genomics and plant breeding is driven by the increasing availability of sequence resources and by technological developments. The simultaneous measurement of the expression of thousands of genes is possible, and comparisons between contrasting genotypes and/or biological states, as well as within segregating populations has become feasible. In genetical genomics, the merger of genetics and genomics, gene expression profiles are quantitatively assessed within a segregating population, and expression quantitative trait loci (eQTL) can be mapped like classical QTLs. Methods and examples of applications related to genetical genomics will be reviewed, with emphasis on hybridisation-based (microarray) and PCR-based (cDNA-AFLP) techniques. Despite the complexity of the molecular mechanisms underlying its development, the study of the cotton fiber has become a trait of primary interest. Several maps, including QTL maps, have been published, structural and metabolic genes related to fiber initiation or elongation have been identified, and several large EST projects have been developed. In this context, the applicability of a genetical genomics approach for the study of cotton fiber quality will be discussed. A new cooperative project with CIRAD, Bayer CropScience and CSIRO, and supported by the French National Agency for Research, ANR, was initiated in 2007. The project aims at the genetic and genomic dissection of fiber quality using an interspecific Gossypium hirsutum X G. barbadense RIL population. Classical QTL mapping of fiber properties will be undertaken using data from different locations, and eQTLs will be detected using both microarray and cDNA-AFLP population-wide profiling. (Résumé d'auteur

    Monitoring drought responses of barley genotypes with semi-robotic phenotyping platform and association analysis between recorded traits and allelic variants of some stress genes

    Get PDF
    Genetic improvement of complex traits such as drought adaptation can be advanced by the combination of genomic and phenomic approaches. Semi-robotic phenotyping platform was used for computer-controlled watering, digital and thermal imaging of barley plants grown in greenhouse. The tested barley variants showed 0–76% reduction in green pixel-based shoot surface area in soil with 20% water content, compared to well-watered plants grown in soil with 60% water content. The barley HvA1 gene encoding the group 3 LEA (Late Embryogenesis Abundant) protein exhibited four (A–D) haplotypes as identified by the EcoTILLING and subsequent DNA sequencing. The green pixel mean value of genotypes with haplotype D was higher than the mean value of the remaining haplotypes, indicating a pivotal role of haplotype D in optimizing the green biomass production under drought condition. In water limitation, the canopy temperature of a highly sensitive genotype was 18.0°C, as opposed to 16.9°C of leaves from a tolerant genotype as measured by thermal imaging. Drought-induced changes in leaf temperature showed moderate correlation with the water use efficiency (r2 = 0.431). The haplotype/trait association analysis based on the t-test has revealed a positive effect of a haplotype B (SNPs:GCCCCTGC) in a gene encoding the barley fungal pathogen induced mRNA for pathogen-related protein (HvPPRPX), on harvest index, thousand grain weight, water use efficiency and grain yield. The presented pilot study established a basic methodology for the integrated use of phenotyping and haplotyping data in characterization of genotype-dependent drought responses in barley
    corecore