40 research outputs found

    Cryptic Disc Structures Resembling Ediacaran Discoidal Fossils from the Lower Silurian Hellefjord Schist, Arctic Norway

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    The Hellefjord Schist, a volcaniclastic psammite-pelite formation in the Caledonides of Arctic Norway contains discoidal impressions and apparent tube casts that share morphological and taphonomic similarities to Neoproterozoic stem-holdfast forms. U-Pb zircon geochronology on the host metasediment indicates it was deposited between 437 Β± 2 and 439 Β± 3 Ma, but also indicates that an inferred basal conglomerate to this formation must be part of an older stratigraphic element, as it is cross-cut by a 546 Β± 4 Ma pegmatite. These results confirm that the Hellefjord Schist is separated from underlying older Proterozoic rocks by a thrust. It has previously been argued that the Cambrian Substrate Revolution destroyed the ecological niches that the Neoproterozoic frond-holdfasts organisms occupied. However, the discovery of these fossils in Silurian rocks demonstrates that the environment and substrate must have been similar enough to Neoproterozoic settings that frond-holdfast bodyplans were still ecologically viable some hundred million years later

    The degree of segmental aneuploidy measured by total copy number abnormalities predicts survival and recurrence in superficial gastroesophageal adenocarcinoma

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    Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC. Methods: We quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses. Results: Recurrent segmental gains and losses involved multiple genes, including: HER2, EGFR, MET, CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those with intermediate CNA counts. These associations persisted when controlling for other prognostic variables. Significance: SNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count). The non-monotonic association of segmental aneuploidy with survival has been described in other tumors. The degree of aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC. Β© 2014 Davison et al

    Epigenetic regulation of prostate cancer

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    Prostate cancer is a commonly diagnosed cancer in men and a leading cause of cancer deaths. Whilst the underlying mechanisms leading to prostate cancer are still to be determined, it is evident that both genetic and epigenetic changes contribute to the development and progression of this disease. Epigenetic changes involving DNA hypo- and hypermethylation, altered histone modifications and more recently changes in microRNA expression have been detected at a range of genes associated with prostate cancer. Furthermore, there is evidence that particular epigenetic changes are associated with different stages of the disease. Whilst early detection can lead to effective treatment, and androgen deprivation therapy has a high response rate, many tumours develop towards hormone-refractory prostate cancer, for which there is no successful treatment. Reliable markers for early detection and more effective treatment strategies are, therefore, needed. Consequently, there is a considerable interest in the potential of epigenetic changes as markers or targets for therapy in prostate cancer. Epigenetic modifiers that demethylate DNA and inhibit histone deacetylases have recently been explored to reactivate silenced gene expression in cancer. However, further understanding of the mechanisms and the effects of chromatin modulation in prostate cancer are required. In this review, we examine the current literature on epigenetic changes associated with prostate cancer and discuss the potential use of epigenetic modifiers for treatment of this disease

    Optic Nerve Changes in Dominant Cone-Rod Dystrophy

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    Genome-wide association analysis identified SNPs closely linked to a gene resistant to Soil-borne wheat mosaic virus

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    Citation: Liu, S., . . . & Bockus, W. (2014). Genome-wide association analysis identified SNPs closely linked to a gene resistant to Soil-borne wheat mosaic virus. Theoretical and Applied Genetics, 127(5), 1039-1047. https//www.doi.org/10.1007/s00122-014-2277-zSoil-borne wheat mosaic virus (SBWMV) disease is a serious viral disease of winter wheat growing areas worldwide. SBWMV infection can significantly reduce grain yield up to 80%. Developing resistant wheat cultivars is the only feasible strategy to reduce the losses. In this study, wheat Infinium iSelect Beadchips with 9K wheat SNPs were used to genotype an association mapping population of 205 wheat accessions. Six new SNPs from two genes were identified to be significantly associated with the gene for SBWMV resistance on chromosome 5D. The SNPs and Xgwm469, a SSR marker that has been reported to be associated with the gene, were mapped close to the gene using F6-derived recombinant inbred lines (RILs) from the cross between a resistant parent β€˜Heyne’ and a susceptible parent β€˜Trego’. Two representative SNPs, wsnp_CAP11_c209_198467 and wsnp_JD_c4438_5568170, from the two linked genes in wheat were converted into KBioscience Competitive Allele-Specific Polymerase (KASP) assays and can be easily used in marker-assisted selection to improve wheat resistance to SBWMV in breeding
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