Phenotyping progenies for complex architectural traits: a strategy for 1-year-old apple trees (Malus x domestica Borkh.)

International audienceThe aim of this study was to define a methodology for describing architectural traits in a quantitative way on tree descendants. Our strategy was to collect traits related to both tree structural organization, resulting from growth and branching, and tree form and then to select among these traits relevant descriptors on the basis of their genetic parameters. Because the complexity of tree architecture increases with tree age, we chose to describe the trees in the early stages of development. The study was carried out on a 1-year-old apple progeny derived from two parent cultivars with contrasted architecture. A large number of variables were collected at different positions and scales within the trees. Broad-sense heritability and genetic correlations were estimated and the within tree variability was analyzed for variables measured on long sylleptic axillary shoots (LSAS). These results were combined to select heritable and not correlated variables. Finally, the selection of variables proposed combines topological with geometric traits measured on both trunks and LSAS: (1) on the trunk, mean internode length, and number of sylleptic axillary shoots; (2) on axillary shoots, conicity, bending, and number of sylleptic axillary shoots born at order 3. The trees of the progeny were partitioned on the basis of these variables. The putative agronomic interest of the selected variables with respect to the subsequent tree development is discussed

Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and death cell in microglial cells

Excessive Zn2+ causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H2O2/Zn2+-induced Ca2+ signalling and cell death in microglial cells. H2O2/Zn2+ induced concentration-dependent increases in cytosolic Ca2+ concentration ([Ca2+]c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H2O2/Zn2+ induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO. Further analysis indicate that Zn2+ induced ROS production, PARP-1 stimulation, increase in the [Ca2+]c and cell death, which were suppressed by chelerythrine, a protein kinase C inhibitor, DPI, a NADPH-dependent oxidase (NOX) inhibitor, GKT137831, a NOX1/4 inhibitor, and Phox-I2, a NOX2 inhibitor. Furthermore, Zn2+-induced PARP-1 stimulation, increase in the [Ca2+]c and cell death were inhibited by PF431396, a Ca2+-sensitive PYK2 inhibitor, and U0126, a MEK/ERK inhibitor. Taken together, our study shows PKC/NOX-mediated ROS generation and PARP-1 activation as an important mechanism in Zn2+-induced TRPM2 channel activation and, TRPM2-mediated increase in the [Ca2+]c to trigger the PYK2/MEK/ERK signalling pathway as a positive feedback mechanism that amplifies the TRPM2 channel activation. Activation of these TRPM2-depenent signalling mechanisms ultimately drives Zn2+-induced Ca2+ overloading and cell death

Time dependent ethnic convergence in colorectal cancer survival in hawaii

BACKGROUND: Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. METHODS: Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese). The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. RESULTS: Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. CONCLUSION: Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated

Is breast cancer prognosis inherited?

Introduction: A genetic component is well established in the etiology of breast cancer. It is not well known, however, whether genetic traits also influence prognostic features of the malignant phenotype. Methods: We carried out a population-based cohort study in Sweden based on the nationwide Multi-Generation Register. Among all women with breast cancer diagnosed from 1961 to 2001, 2,787 mother-daughter pairs and 831 sister pairs with breast cancer were identified; we achieved complete follow-up and classified 5-year breast cancer-specific prognosis among proband (mother or oldest sister) into tertiles as poor, intermediary, or good. We used Kaplan-Meier estimates of survival proportions and Cox models to calculate relative risks of dying from breast cancer within 5 years depending on the proband's outcome. Results: The 5-year survival proportion among daughters whose mothers died within 5 years was 87% compared to 91% if the mother was alive (p = 0.03). Among sisters, the corresponding proportions were 70% and 88%, respectively (p = 0.001). After adjustment for potential confounders, daughters and sisters of a proband with poor prognosis had a 60% higher 5-year breast cancer mortality compared to those of a proband with good prognosis (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.2 to 2.2; p for trend 0.002). This association was slightly stronger among sisters (HR, 1.8; 95% CI, 1.0 to 3.4) than among daughters (HR, 1.6; 95% CI, 1.1 to 2.3). Conclusion: Breast cancer prognosis of a woman predicts the survival in her first-degree relatives with breast cancer. Our novel findings suggest that breast cancer prognosis might be inherited

Residence, income and cancer hospitalizations in British Columbia during a decade of policy change

BACKGROUND: Through the 1990s, governments across Canada shifted health care funding allocation and organizational foci toward a community-based population health model. Major concerns of reform based on this model include ensuring equitable access to health and health care, and enhancing preventive and community-based resources for care. Reforms may act differentially relative to specific conditions and services, including those geared to chronic versus acute conditions. The present study therefore focuses on health service utilization, specifically cancer hospitalizations, in British Columbia during a decade of health system reform. METHODS: Data were drawn from the British Columbia Linked Health Data resource; income measures were derived from Statistics Canada 1996 Census public use enumeration area income files. Records with a discharge (separation) date between 1 January 1991 and 31 December 1998 were selected. All hospitalizations with ICD-9 codes 140 through 208 (except skin cancer, code 173) as principal diagnosis were included. Specific cancers analyzed include lung; colorectal; female breast; and prostate. Hospitalizations were examined in total (all separations), and as divided into first and all other hospitalizations attributed to any given individual. Annual trends in age-sex adjusted rates were analyzed by joinpoint regression; longitudinal multivariate analyses assessing association of residence and income with hospitalizations utilized generalised estimating equations. Results are evaluated in relation to cancer incidence trends, health policy reform and access to care. RESULTS: Age-sex adjusted hospitalization rates for all separations for all cancers, and lung, breast and prostate cancers, decreased significantly over the study period; colorectal cancer separations did not change significantly. Rates for first and other hospitalizations remained stationary or gradually declined over the study period. Area of residence and income were not significantly associated with first hospitalizations; effects were less consistent for all and other hospitalizations. No interactions were observed for any category of separations. CONCLUSIONS: No discontinuities were observed with respect to total hospitalizations that could be associated temporally with health policy reform; observed changes were primarily gradual. These results do not indicate whether equity was present prior to health care reform. However, findings concur with previous reports indicating no change in access to health care across income or residence consequent on health care reform