Model analysis of temperature impact on the Norway spruce provenance specific bud burst and associated risk of frost damage

The annual growth cycle of boreal trees is synchronized with seasonal changes in photoperiod and temperature. A warmer climate can lead to an earlier bud burst and increased risk of frost damage caused by temperature backlashes. In this study we analysed site- and provenance specific responses to interannual variation in temperature, using data from 18 Swedish and East-European provenances of Norway spruce (Picea abies), grown in three different sites in southern Sweden. The temperature sum requirements for bud burst, estimated from the provenance trials, were correlated with the provenance specific place of origin, in terms of latitudinal and longitudinal gradients. Frost damage had a significant effect on tree height development. Earlier timing of bud burst was linked to a higher risk of frost damage, with one of the sites being more prone to spring frost than the other two. The estimated provenance specific temperature sum requirements for bud burst were used to parametrize a temperature sum model of bud burst timing, which was then used together with the ensemble of gridded climate model data (RCP8.5) to assess the climate change impact on bud burst and associated risk of frost damage. In this respect, the simulated timing of bud burst and occurrence of frost events for the periods 2021-2050 and 2071-2100 were compared with 1989-2018. In response to a warmer climate, the total number of frost events in southern Sweden will decrease, while the number of frost events after bud burst will increase due to earlier bud burst timing. The provenance specific assessments of frost risk under climate change can be used for a selection of seed sources in Swedish forestry. In terms of selecting suitable provenances, knowledge on local climate conditions is of importance, as the gridded climate data may differ from local temperature conditions. A comparison with temperature logger data from ten different sites indicated that the gridded temperature data were a good proxy for the daily mean temperatures, but the gridded daily minimum temperatures tended to underestimate the local risk of frost events, in particular at the measurements 0.5 m above ground representing the height of newly established seedlings

Controlled exposure to diesel exhaust and traffic noise - Effects on oxidative stress and activation in mononuclear blood cells

Particulate air pollution increases risk of cancer and cardiopulmonary disease, partly through oxidative stress. Traffic-related noise increases risk of cardiovascular disease and may cause oxidative stress. In this controlled random sequence study, 18 healthy subjects were exposed for 3h to diesel exhaust (DE) at 276μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine were unaltered. In auxiliary ex vivo experiments whole blood was incubated with particles from the exposure chamber for 3h without effects on DNA damage in PBMCs or intracellular reactive oxygen species production and expression of CD11b and CD62L adhesion molecules in leukocyte subtypes

Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

ObjectiveOvarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30–50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome.MethodsGene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2). Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3) was used for validation by immunohistochemistry and chromogenic in situ hybridization.ResultsGene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors.ConclusionOCCCs appear genetically heterogeneous, but harbor frequent alterations in chromatin remodeling genes. Overexpression of TFAP2A and ERBB2 was observed on the mRNA level in relation to other ovarian cancer subtypes. However, overexpression of ERBB2 was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct biological features of OCCC discovered here may provide a basis for novel targeted treatment strategies

Effect of commercial rye whole-meal bread on postprandial blood glucose and gastric emptying in healthy subjects

<p>Abstract</p> <p>Background</p> <p>The intake of dietary fibre has been shown to reduce the risk of developing diabetes mellitus. The aim of this study was to compare the effects of commercial rye whole-meal bread containing whole kernels and white wheat bread on the rate of gastric emptying and postprandial glucose response in healthy subjects.</p> <p>Methods</p> <p>Ten healthy subjects took part in a blinded crossover trial. Blood glucose level and gastric emptying rate (GER) were determined after the ingestion of 150 g white wheat bread or 150 g whole-meal rye bread on two different occasions after fasting overnight. The GER was measured using real-time ultrasonography, and was calculated as the percentage change in antral cross-sectional area 15 and 90 minutes after completing the meal.</p> <p>Results</p> <p>No statistically significant difference was found between the GER values or the blood glucose levels following the two meals when evaluated with the Wilcoxon signed rank sum test.</p> <p>Conclusion</p> <p>The present study revealed no difference in postprandial blood glucose response or gastric emptying after the ingestion of rye whole-meal bread compared with white wheat bread.</p> <p>Trial registration</p> <p>NCT00779298</p

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Intrinsic subtypes and prognostic implications in epithelial ovarian cancer

Ovarian cancer is the seventh most common cancer in women globally, with approximately 240,000 new cases annually. Although a rare disease, it is the most lethal gynecologic malignancy. Unspecific symptoms result in late diagnosis and a generally poor prognosis. However, ovarian cancer is a heterogeneous disease comprising different disease entities, which is of importance in clinical decision-making as well as in research. This thesis describes explorative approaches to investigate the ovarian cancer heterogeneity in a hereditary ovarian cancer subset and in histopathological and molecular subtypes of ovarian cancer. In study I, a gene expression profile differentiating the rare subgroup of Lynch syndrome-associated ovarian cancer from a matched sporadic cohort was identified. The Lynch syndrome-related expression profile was associated with proliferation and cell death processes. An external dataset was used to refine the gene expression profile, but validation with immunohistochemical staining of key proteins did not reveal any differences between the hereditary and sporadic cases. A distinct cluster of hereditary serous and endometrioid cancers was seen, whereas clear cell carcinomas (OCCCs) clustered together, whether hereditary or sporadic. In study II, gene expression profiling of OCCCs revealed extensive inter-tumor heterogeneity. Targeted deep sequencing of 60 cancer-related genes in an OCCC cohort revealed frequent mutations of chromatin remodeling genes, including mutations not previously reported in ovarian cancer. These results remain to be validated. Study III outlined gene expression profiles in malignant, borderline, and benign serous ovarian tumors. Pre-defined molecular subtypes of ovarian cancer as well as intrinsic breast cancer subtypes were applied to our cohort. Associations between the most aggressive ovarian cancer subtypes and the basal-like breast cancer subtype were identified. The results were validated using a large, external dataset. Furthermore, associations between borderline ovarian tumors and the luminal A breast cancer subtype were discovered. The luminal A breast cancer subtype characterizes hormone receptor positive breast cancer. In study IV, we therefore outlined the protein expression of estrogen receptor (ER) α, ERβ, the progesterone receptor (PR), and the androgen receptor (AR) as well as the prognostic effect of receptor expression in serous and endometrioid ovarian cancer. Expression of PR and AR was associated with a favorable prognosis, and co-expression of PR and AR conferred an additional prognostic benefit. The mRNA levels of the encoding genes were investigated in the molecular subtypes of ovarian cancer using an external dataset. The expression varied between the different subtypes, but no prognostic benefit of dual high PGR and AR levels were revealed. In conclusion these studies further characterize the ovarian cancer heterogeneity, and support that future ovarian cancer studies need to be stratified for both histopathologic subtypes and molecular feature