The contribution of insects to global forest deadwood decomposition

The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks. The decomposition of deadwood is largely governed by climate with decomposer groups—such as microorganisms and insects—contributing to variations in the decomposition rates. At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood. Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect—including the direct consumption by insects and indirect effects through interactions with microorganisms—insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and −0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

Refined histopathological predictors of BRCA1 and BRCA2 mutation status : a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Abstract Introduction The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. Results ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). Conclusions These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management

Plant reproduction in the alpine landscape : reproductive ecology, genetic diversity and gene flow of the rare monocarpic "Campanula thyrsoides" in the Swiss Alps

Aims & Objectives The work presented in this thesis forms part of a larger project “How patchy habitat and isolation affect alpine plant life: genetic diversity, gene flow and mating systems”, which includes the PhD studies of Patrick Kuss and the author under the supervision of Professor Jürg Stöcklin. This doctoral thesis investigates the consequences of the natural fragmentation and patchiness of alpine landscapes on the life of alpine plant populations. The central focus of the thesis is on the mating system, the role of inbreeding and/or outbreeding depression, genetic diversity and geographic structure within and among populations of the rare Alpine monocarpic perennial Campanula thyrsoides. The main objectives and research questions addressed are: • Is Campanula thyrsoides self-compatible (SI) and if not, does the SI system break down with flower age? Do inbred C. thyrsoides offspring in the common garden suffer from inbreeding depression? • Do we find a distance related inbreeding depression (poorer reproducive output) or outbreeding depression (increased reproductive output) in field populations of C. thyrsoides following crosses of different crossing distances (selfing, 1m, 10m, 100m and among distant populations)? • How much genetic diversity exists within populations of C. thyrsoides and how does it relate to population size and altitude? Has the natural habitat fragmentation let to strong genetic differentiation and restricted gene flow among populations of C. thyrsoides resulting in a pronounced geographic structure? Study species In order to seek answers to our research questions, we choose to study a yellow bellflower; Campanula thyrsoides. The choice was based on the information that C. thyrsoides is a rare plant species, which is only found on calcarious soils within the European Alps and adjacent mountain ranges (Aeschimann et al. 2005). The plants selectiveness for carbonate bearing soils together with the fact that its seeds are not adapted to long-distance dispersal (Tackenberg 2003) are the main reasons for the isolation and small sizes of many of its populations. These population characteristics, therefore, made C. thyrsoides a suitable study species. Another important characteristic of C. thyrsoides, and one of the main reasons for its inclusion in the study is because it is a monocarpic perennial which flowers once and subsequently dies (Jäger 2000). Monocarpic plants species, which are more commonly found in subtropical and tropical mountain systems (e.g. the giant rosettes of Puya spp, Espeletia spp., Echium spp. etc., Smith & Young 1987; Young & Augspurger 1991) are rare amidst the temperate alpine flora (for the Alps, see Aeschimann et al. 2005). Monocarpy can promote genetic differentiation between populations by reducing the effective population size due to a shorter generation time and lower density of populations (Loveless & Hamrick 1984; Vitalis et al. 2004). When studying the effects of population isolation and habitat fragmentation on plant reproduction (e.g. mating system and inbreeding depression), it is, moreover, ideal to study a Campanula species. Although most Campanula species are selfincompatible and allogamous (Nyman 1993), both a break-down in the SI system with flower age (Vogler et al. 1998) and an evolution towards complete self-compatibility (Ægisdóttir & Thórhallsdóttir 2006) have been recorded. Design We studied the reproductive ecology and genetic diversity of Campanula thyrsoides by firstly setting up pollination experiments in the common garden and in the field and secondly by sampling leaf material in 32 field populations in Switzerland. In the common garden study, we set up a pollination experiment in order to study the breeding system of C. thyrsoides, including the consequences of selfing, half-sibling crossings and outcrossing on reproductive output and seedling performance. Moreover, field experiments in four populations were set up in the Swiss Alps in order to study the effect of different crossing distances on reproduction in C. thyrsoides and to see if evidence would be found of hidden inbreeding depression or outbreeding depression following large-distance crossings compared to within-population crossings. In addition, we studied the genetic diversity, gene flow and geographical structure within and among 32 field populations of C. thyrsoides in Switzerland, covering both large geographical and altitudinal ranges. The genetic study was conducted using 5 co-dominant microsatellite markers. In addition, we studied the genetic diversity in C. thyrsoides and two other alpine plants using random amplified polymorphic DNA (RAPD) marker as well as studing the evolutionary demography of C. thyrsoides

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

IntroductionThe distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.MethodsSelection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.ResultsER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).ConclusionsThese results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management

Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1.

The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ERα to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease