Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis

BACKGROUND: The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours. METHODS: Two cohorts were compared: one was a group with young-onset PrCa, tested for germline BRCA2 mutations (6 of 263 cases had a germline BRAC2 mutation), and the second was a validation set consisting of a clinical set from Manchester of known BRCA2 mutuation carriers (15 cases) with PrCa. Survival data were compared with a control series of patients in a single clinic as determined by Kaplan-Meier estimates. Loss of heterozygosity was tested for in the DNA of tumour tissue of the young-onset group by typing four microsatellite markers that flanked the BRCA2 gene, followed by sequencing. RESULTS: Median survival of all PrCa cases with a germline BRCA2 mutation was shorter at 4.8 years than was survival in controls at 8.5 years (P = 0.002). Loss of heterozygosity was found in the majority of tumours of BRCA2 mutation carriers. Multivariate analysis confirmed that the poorer survival of PrCa in BRCA2 mutation carriers is associated with the germline BRCA2 mutation per se. CONCLUSION: BRCA2 germline mutation is an independent prognostic factor for survival in PrCa. Such patients should not be managed with active surveillance as they have more aggressive disease. British Journal of Cancer (2010) 103, 918-924. doi:10.1038/sj.bjc.6605822 www.bjcancer.com Published online 24 August 2010 (C) 2010 Cancer Research U

ELAC2 polymorphisms and prostate cancer risk: a meta-analysis based on 18 case–control studies

Polymorphisms in the elaC homolog-2 (ELAC2)/HPC2 gene have been hypothesized to alter the risk of prostate cancer. However, the results of the related published studies remained conflicting. We performed a meta-analysis of 18 studies evaluating the association between ELAC2 Ser217Leu and Ala541Thr polymorphisms and prostate cancer risk. Overall, ELAC2 Leu217 allele was associated with increased prostate cancer risk as compared with the Ser217 allele (odds ratio (OR)=1.13, 95% confidence interval (CI): 1.03–1.24, P=0.019 for heterogeneity), as well as in the heterozygote comparison (OR=1.21, 95% CI: 1.07–1.36, P=0.034 for heterogeneity) and the dominant genetic model (OR=1.20, 95% CI: 1.07–1.35, P=0.025 for heterogeneity). Furthermore, the ELAC2 Thr541 allele was associated with increased prostate cancer risk as compared with the Ala541 allele (OR=1.22, 95% CI: 1.00–0.48, P=0.131 for heterogeneity). In the stratified analyses for Ser217Leu polymorphism, there was significantly increased prostate cancer risk in Asian and Caucasian populations, and studies using sporadic and familial prostate cancer cases. Similar result was found in the Asian population in the stratified analyses for Ala541Thr polymorphism. This meta-analysis showed evidence that ELAC2 Ser217Leu and Ala541Thr polymorphisms were associated with prostate cancer risk, and might be low-penetrance susceptibility markers of prostate cancer

Morphological and molecular identification of fungi associated with South African apple core rot

CITATION: Basson, E., Meitz-Hopkins, J. C. & Lennox, C. L. 2018. Morphological and molecular identification of fungi associated with South African apple core rot. European Journal of Plant Pathology, 153:849-868, doi:10.1007/s10658-018-1601-x.The original publication is available at https://link.springer.comCore rot is a major contributor to postharvest losses in apples worldwide. Pathogens most commonly associated with the disease are Alternaria spp. and Penicillium spp. Although both genera show specific morphological characteristics, they can be difficult to identify to species level. In this study, Alternaria spp. (49) and Penicillium spp. isolates (97), associated with pre- and post-harvest apple core rot-symptoms and isolates from potential inoculum sources were identified using molecular methods. Initially, dry core rot causing Alternaria spp. were identified morphologically in an average of 70% of infected fruit pre-harvest and 32% postharvest. Furthermore, 78% of mouldy core rot causing pathogens were identified as Alternaria spp. preharvest and 40% postharvest. Wet core rot was associated with Penicillium spp. in 64% of cases preharvest and 36% postharvest. Species identity of a selection of samples was confirmed using the endopolygalacturonase (endo-PG) gene, the ITS region, and the anonymous genomic regions (OPA1–3, 2–1), which resulted in the identification of A. alternata, A. arborescens, A. dumosa, A. eureka and A. tenuissima. Penicillium species were identified through ITS sequencing and partial beta-tubulin polymerase chain reaction – random fragment length polymorphisms (PCR-RFLP) for the samples collected from wet core rot symptoms. Phylogenetic analyses separated the Alternaria spp. into five clades, including three separate clades for A. alternata, A. tenuissima and A. arborescens, respectively. This is the first report of A. eureka and P. polonicum as potential core rot pathogens. Phylogenetic analysis identified Penicillium ramulosum and P. expansum as the most commonly occurring species associated with WCR symptoms.https://link.springer.com/article/10.1007/s10658-018-1601-xPost prin

Morphological and phylogenetic analyses of Pythium species in South Africa

The genus Pythium is important in agriculture, since it contains many plant pathogenic species, as well as species that can promote plant growth and some that have biocontrol potential. In South Africa, very little is known about the diversity of Pythium species within agricultural soil, irrigation and hydroponic systems. Therefore, the aim of the study was to characterise a selection of 85 Pythium isolates collected in South Africa from 1991 through to 2007. The isolates were characterised morphologically as well as through sequence and phylogenetic analyses of the internal transcribed spacer regions (ITS) and the 5.8S gene of the nuclear ribosomal DNA. Phylogenetic analyses showed that the isolates represented ten of the 11 published Pythium clades [Lévesque & De Cock, 2004. Molecular phylogeny and taxonomy of the genus Pythium. Mycological Research 108: 1363-1383]. Characterisation of isolates in clade D and J suggested that the phylogenetic concept of Pythium acanthicum and Pythium perplexum respectively, needs further investigation in order to enable reliable species identification within these clades. Our phylogenetic analyses of Pythium species in clade B also showed that species with globose sporangia group basal within this clade, and are not dispersed within the clade as previously reported. The 85 South African isolates represented 34 known species, of which 20 species have not been reported previously in South Africa. Additionally, three isolates (PPRI 8428, 8300 and 8418) were identified that may each represent putative new species, Pythium sp. WJB-1 to WJB-3. © 2009 The British Mycological Society.Articl

Use of sulfur dioxide to reduce postharvest decay and preserve the quality of fresh tomatoes

Tomatoes are an important and versatile crop with a short shelf life. Postharvest losses due to fruit decay and handling are reportedly as high as 30–50% globally; therefore, the agricultural sector would benefit from solutions that target the preservation of crops such as tomatoes. In this study, we investigated the potential use of sulfur dioxide (SO2) to provide postharvest protection against fungal decay in tomatoes whilst maintaining the quality of tomato fruit. Three tomato varieties packed as bulk (3–5 kg) cartons were exposed to SO2-generating sheets applied as either a top sheet over the fruit or a bottom sheet placed on the base of the carton before packing the fruit on the top. The results show that the application of SO2-generating sheets reduced the natural progression of decay on ‘Roma’ tomatoes by up to 60% and up to 80% on ‘Rosa’ tomatoes. Only marginal decay control was observed on ‘Round’ tomatoes. The top sheet application rendered the best results, as the application of the bottom sheet resulted in phytotoxicity in the form of SO2 damage. SO2 application reduced fruit shrivelling, especially when tomatoes were stored at higher temperatures during their shelf life. The application of SO2 on the tomatoes did not have any negative effects on fruit firmness. The results of this study provide a case to further explore the use of SO2-generating sheets on tomatoes to prevent postharvest decay. Differences in varietal physiology may be key to the successful application of this technology. Significance: Tomatoes are a crop that is highly susceptible to postharvest decay. These effects lie mainly with the end consumer. Besides the monetary loss of buying a commodity that rots quickly, pathogens infecting tomatoes are known to produce mycotoxins that pose a risk to human health. With food availability and safety concerns, the application of a product that could reduce these concerns would be beneficial to the agricultural sector

Natural variation reveals key amino acids in a downy mildew effector that alters recognition specificity by an Arabidopsis resistance gene

RPP13, a member of the cytoplasmic class of disease resistance genes, encodes one of the most variable Arabidopsis proteins so far identified. This variability is matched in ATR13, the protein from the oomycete downy mildew pathogen Hyaloperonospora parasitica recognized by RPP13, suggesting that these proteins are involved in tight reciprocal coevolution. ATR13 exhibits five domains: an N-terminal signal peptide, an RXLR motif, a heptad leucine/isoleucine repeat, an 11-amino-acid repeated sequence and a C-terminal domain. We show that the conserved RXLR-containing domain is dispensable for ATR13-mediated recognition, consistent with its role in transport into the plant cytoplasm. Sequencing ATR13 from 16 isolates of H. parasitica revealed high levels of amino acid diversity across the entire protein. The leucines/isoleucines of the heptad leucine repeat were conserved, and mutation of particular leucine or isoleucine residues altered recognition by RPP13. Natural variation has not exploited this route to detection avoidance, suggesting a key role of this domain in pathogenicity. The extensive variation in the 11-amino-acid repeat units did not affect RPP13 recognition. Domain swap analysis showed that recognition specificity lay in the C-terminal domain of ATR13. Variation analyses combined with functional assays allowed the identification of four amino acid positions that may play a role in recognition specificity. Site-directed mutagenesis confirmed that a threonine residue is absolutely required for RPP13 recognition and that recognition can be modulated by the presence of either an arginine or glutamic acid at other sites. Mutations in these three amino acids had no effect on the interaction of ATR13 with a resistance gene unlinked to RPP13, consistent with their critical role in determining RPP13-Nd recognition specificity

Reynolds-Averaged Navier-Stokes Calculations Of Unsteady Turbulent Flow

In this study, a combination of the unsteady incompressible Navier-Stokes equations in vorticityvelocity formulation and the Algebraic Stress Model (ASM) of Gatski and Speziale (1996) is employed for Unsteady Reynolds Averaged Navier-Stokes (URANS) calculations of turbulent boundary layer flows. The Navier-Stokes equations are solved using a fourth-order compact difference scheme in space and a fourth-order Runge-Kutta method in time. The highly accurate numerical method greatly reduces the possibility of contamination of the results by second-order artificial dissipation from the numerical schemes. A flat plate boundary layer subjected to a strong adverse pressure gradient with laminar separation and turbulent reattachment is investigated. Performing URANS calculations for this flow, we found that unsteady vortical structures remain in the flow field despite the large "effective eddy viscosity" produced by the turbulence model (ASM). This is due to the fact that a special function is ..

A Multiple Regime Nonlinear Asymmetric AR(p)-GARCH(1,1) Model

In this article a multiple regime extension for the Heston-Nandi GARCH(1,1) model is presented to describe the asymmetries and intermittent dynamics in financial volatility. The statistical properties and the estimation of their parameters are addressed in detail. The number of regimes in the model is determined through a statistical procedure based on a novel robust Lagrange Multiplier (LM) specification. The ability of the model to forecast financial market volatility is empirically compared to other GARCH models for a set comprising some of the major world stock indexes and their corresponding foreign exchange rates during the recent financial crisis