Genetic and environmental variation in seed, cone and progeny characteristics of black spruce clones in a northern Ontario seed orchard

Genetic and environmental variance in cone and seed properties and early progeny growth of Picea mariana (Mill.) B.S.P. clones were evaluated using cones and seed from two to three ramets of 19 clones each growing in a northern Ontario grafted clonal seed orchard. A cone analysis and a germination test were conducted to estimate variation among clones and among ramets within clones. Variation in growth of 19 open-pollinated families growing under two fertilizer regimes in a greenhouse was evaluated after three, four and five months of test establishment. Mean cone volume and mean cone length were found to be 2.2 cm[superscript 3] and 24.4 mm, respectively. The mean for number of seed per cone was 71, although only 18% of these seeds were filled. Nested analyses of variance indicated that clones accounted for 23% to 39% of the total variation in cone size and seed yield per cone. Variation among ramets within clones for these characteristics accounted for 13% to 19% of total variance. The average germination percent, based on filled seed, was 68% and was completed (90%) after 11 days. Genetic variance in germination percent and germination speed acccounted for 67% and 21% of the total variance, respectively. For germination percent and germination speed, 18% and 33% of the total variation, respectively, were due to ramets within clones. In the progeny test, family heights were highly significant at all three ages. At five months family height means ranged from 30 cm to 34 cm and from 11 cm to 14 cm at the low and high fertilizer level, respectively, Ramet-within-clone effects were only significant after three and four months, when seedling heights were significantly correlated with seed weights. Family-fertilizer interactions were not significant at all three ages, although the variance component for this source of variation increased substantially towards the end of the test period

Linkage disequilibrium vs. pedigree: Genomic selection prediction accuracy in conifer species

Background The presupposition of genomic selection (GS) is that predictive accuracies should be based on population-wide linkage disequilibrium (LD). However, in species with large, highly complex genomes the limitation of marker density may preclude the ability to resolve LD accurately enough for GS. Here we investigate such an effect in two conifer species with similar to 20 Gbp genomes, Douglas-fir (Pseudotsuga menziesiiMirb. (Franco)) and Interior spruce (Picea glauca(Moench) Voss xPicea engelmanniiParry ex Engelm.). Random sampling of markers was performed to obtain SNP sets with totals in the range of 200-50,000, this was replicated 10 times. Ridge Regression Best Linear Unbiased Predictor (RR-BLUP) was deployed as the GS method to test these SNP sets, and 10-fold cross-validation was performed on 1,321 Douglas-fir trees, representing 37 full-sib F(1)families and on 1,126 Interior spruce trees, representing 25 open-pollinated (half-sib) families. Both trials are located on 3 sites in British Columbia, Canada. Results As marker number increased, so did GS predictive accuracy for both conifer species. However, a plateau in the gain of accuracy became apparent around 10,000-15,000 markers for both Douglas-fir and Interior spruce. Despite random marker selection, little variation in predictive accuracy was observed across replications. On average, Douglas-fir prediction accuracies were higher than those of Interior spruce, reflecting the difference between full- and half-sib families for Douglas-fir and Interior spruce populations, respectively, as well as their respective effective population size. Conclusions Although possibly advantageous within an advanced breeding population, reducing marker density cannot be recommended for carrying out GS in conifers. Significant LD between markers and putative causal variants was not detected using 50,000 SNPS, and GS was enabled only through the tracking of relatedness in the populations studied. Dramatically increasing marker density would enable said markers to better track LD with causal variants in these large, genetically diverse genomes; as well as providing a model that could be used across populations, breeding programs, and traits

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Coastal Douglas-fir provenance variation: patterns and predictions for British Columbia seed transfer

• We evaluated performance variability in two series of provenance trials of Pseudotsuga menziesii var. menziesii. EP 480 included 16 reciprocal provenances planted from British Columbia to Oregon, measured up to age 45. EP 599.03 featured five common provenances, plus the local source, planted at 23 British Columbia sites, measured up to age 33. • Although residual variance was high, site accounted for 31 to 60% of the volume variance, while provenance accounted for 1–6%. Interactions were also significant across ages and trials. Genotype-environment interaction was evident in EP 599.03, but not EP 480, which may reflect differences in experimental design. • The worst provenances always ranked low across sites and over time. No geographic or climatic (annual, seasonal, monthly) variables consistently explained patterns of volume across sites or ages, singly or in combination for either trial, similar to findings from other studies of coastal Douglas-fir. Provenances from Washington to central Oregon often performed as well as the local provenance or better at British Columbia trial sites. Populations from higher elevations, poor sites and submaritime provenances were less vigorous. • Results support maintaining elevational and ecotypic transfer limits, emphasizing site-specific decision making, and permitting wider latitudinal transfer on similar quality sites

2013. Multivariate detection of hybridization using conifer terpenes II: analysis of terpene inheritance patterns in Pseudotsuga menziesii F1 hybrids. Phytologia 95:42–57

ABSTRACT The compositions of the volatile leaf oils of Pseudotsuga menziesii var. menziesii and var. glauca and their hybrids were examined and utilized to examine multi-variate methods for the detection of hybridization. The first cross (coastal parent 226 x inland parent 267) produced four hybrids whose oils were much like the inland (var. glauca) parent, and 6 hybrids with composition more intermediate between the parents. Eleven of the terpenes were generally intermediate in the hybrids, whereas the other 15 terpenes were transgressive. Truncation of the terpene values to those of the maximum or minimum value of the parents improved PCO ordination using character weights of Fs from ANOVA. A second set of hybrids between coastal parent 517 x intermediate parent 521 yielded similar kinds of variation in the terpenes of the hybrids. Only 2 compounds were intermediate between parents whereas 8 terpenoids showed dominance with values like one of the parents. Nine of the terpenes and percent oil yield were transgressive to both parents. Using F weighting and truncation of transgressives, improved the ordination separating parents from hybrids. However, again, the hybrids were ordinated in two groups. Selecting a balanced set of discriminating terpenes, aided in ordination. In a study of natural field hybridization, the terpenes should be useful to classify the hybrids, but it may be difficult to accurately classify back-crossed or F 2 individuals. Published on-line: www.phytologia.org Phytologia 95(1): 42-57 (Feb. 1, 2013)

Supplementary Material Douglas-fir data [Conjunto de datos]

Supplementary information of the three Douglas-fir trials, family numbers, and pedigree data including identity information of trees, fathers, and mothers of the paper entitled: Identification and joint modeling of competition effects and environmental heterogeneity in three Douglas-fir (Pseudotsuga menziesii var. menziesii) trials. Tree genetics & genomes 12 (6) : 102. (December 2016)Instituto de Recursos BiológicosFil: Cappa, Eduardo Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Cappa, Eduardo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stoehr, Michael U. British Columbia Ministry of Forests. Lands and Natural Resource Operations. Tree Improvement Branch; CanadáFil: Chang-Yi, Xie. British Columbia Ministry of Forests. Lands and Natural Resource Operations. Tree Improvement Branch; CanadáFil: Yanchuk, Alvin D. British Columbia Ministry of Forests. Lands and Natural Resource Operations. Tree Improvement Branch; Canad

validation genotypes

SNP data for 136 samples from Jordan River validation population (69951 SNPs)