Short Communication. Comparing flammability traits among fire-stricken (low elevation) and non fire-stricken (high elevation) conifer forest species of Europe: A test of the Mutch hypothesis

Aim of study. The flammability of the main coniferous forest species of Europe, divided into two groups according to their fire regime and altitudinal distribution, was tested in an effort to detect species-specific differences that may have an influence on community-wide fire regimes.Area of study. Conifer species comprising low- and high-elevation forests in Europe.Materials and Methods. The following conifer species were tested: low elevation; Pinus halepensis (Aleppo pine), Pinus brutia (Turkish pine), Pinus pinaster (maritime pine), Pinus pinea (stone pine) and Cupressus sempervirens (cypress), high elevation (i.e., above 600 m a.s.l.); Pinus sylvestris (Scots pine), Abies alba (white fir), Picea excelsa (Norway spruce), Abies borissii regis (Macedonian fir) and Pinus nigra (black pine). Flammability assessment (time-to-ignition and ignition temperature) was conducted by an innovative ignition apparatus, heat content was measured with an IKA Adiabatic Bomb Calorimeter and ash content by heating 5 g of plant material in a muffle furnace at 650ºC for 1 h. Differences among species was statistically analysed by Duncan’s multiple comparison test.Main results. The results did not distinguish separate groups among traits between fire- and non-fire-stricken communities at the individual species level.Research highlights. Differences in fire regimes among low and high elevation conifer forests could be attributed either to differences in flammability of the plant communities as a whole (i.e., fuelbed or canopy properties vs. individual fuel properties) or to other factors (climatic or anthropogenic).Key words: flammability; ignitability; heat content; ash content; conifer species; Mutch hypothesis

Greece's Sudden Faltering Economy: From Boom to Bust With special reference to the debt problem

In this paper, we deal with theoretical propositions and empirical evidence that are needed to explain the paradox of rapid GDP growth in the face of the dismal competitiveness of the Greek economy during 1995-2008. We show how Greece’s economy structural weaknesses have hit the domestic economy and we investigate their impact on the current turmoil of the economy. We show that the previous favourable global economic environment acted as a locomotive to domestic growth, and now that it is gone, structural problems of poor governance, low competitiveness and a ballooning public deficit and debt, have come to the surface. Also, in the context of debt sustainability we look at the recent actions to reduce debt that are taken by the Growth and Stability Program. We construct five scenarios regarding the level of public debt at the end of the 2011-2015 period that is commonly accepted that Greece will return to global financial markets to finance its debt. We find that only under a very optimistic scenario of robust growth of the economy based on structural and institutional reforms that boost productivity, significantly improve competitiveness, and boost the financial sector as described in the Growth and Stability Program along with a successful privatization of 50 billion euros the public debt to gdp ratio can reach the 60% threshold that the financial markets find comfortable. We offer a specific explanation of the current unfortunate state of the economy and we briefly suggest avenues of necessary progressive reforms to overcome it

Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment

Introduction: The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised. Methods: Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made. Results: Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species. Conclusions: These results provide new insights into genetic regulatory mechanisms of mammary development, particularly identification of novel potential regulators of mammary fate and mesenchymal-epithelial cross-talk. Since cancers may represent diseases of mesenchymal-epithelial communications, we anticipate these results will provide foundations for further studies into the fundamental links between developmental, stem cell and breast cancer biology

Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer

Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function

Plasticity in dendroclimatic response across the distribution range of Aleppo pine (Pinus halepensis)

We investigated the variability of the climate-growth relationship of Aleppo pine across its distribution range in the Mediterranean Basin. We constructed a network of tree-ring index chronologies from 63 sites across the region. Correlation function analysis identified the relationships of tree-ring index to climate factors for each site. We also estimated the dominant climatic gradients of the region using principal component analysis of monthly, seasonal, and annual mean temperature and total precipitation from 1,068 climatic gridpoints. Variation in ring width index was primarily related to precipitation and secondarily to temperature. However, we found that the dendroclimatic relationship depended on the position of the site along the climatic gradient. In the southern part of the distribution range, where temperature was generally higher and precipitation lower than the regional average, reduced growth was also associated with warm and dry conditions. In the northern part, where the average temperature was lower and the precipitation more abundant than the regional average, reduced growth was associated with cool conditions. Thus, our study highlights the substantial plasticity of Aleppo pine in response to different climatic conditions. These results do not resolve the source of response variability as being due to either genetic variation in provenance, to phenotypic plasticity, or a combination of factors. However, as current growth responses to inter-annual climate variability vary spatially across existing climate gradients, future climate-growth relationships will also likely be determined by differential adaptation and/or acclimation responses to spatial climatic variation. The contribution of local adaptation and/or phenotypic plasticity across populations to the persistence of species under global warming could be decisive for prediction of climate change impacts across populations. In this sense, a more complex forest dynamics modeling approach that includes the contribution of genetic variation and phenotypic plasticity can improve the reliability of the ecological inferences derived from the climate-growth relationships.This work was partially supported by Spanish Ministry of Education and Science co-funded by FEDER program (CGL2012-31668), the European Union and the National Ministry of Education and Religion of Greece (EPEAEK- Environment – Archimedes), the Slovenian Research Agency (program P4-0015), and the USDA Forest Service. The cooperation among international partners was supported by the COST Action FP1106, STREeSS

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms.

Multiple myeloma (MM) is a biologically heterogeneous malignancy, however, the mechanisms underlying this complexity are incompletely understood. We report an analysis of the whole-genome sequencing of 765 MM patients from CoMMpass. By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Wildfire Risk Assessment in a Typical Mediterranean Wildland–Urban Interface of Greece

The purpose of this study was to assess spatial wildfire risk in a typical Mediterranean wildland–urban interface (WUI) in Greece and the potential effect of three different burning condition scenarios on the following four major wildfire risk components: burn probability, conditional flame length, fire size, and source–sink ratio. We applied the Minimum Travel Time fire simulation algorithm using the FlamMap and ArcFuels tools to characterize the potential response of the wildfire risk to a range of different burning scenarios. We created site-specific fuel models of the study area by measuring the field fuel parameters in representative natural fuel complexes, and we determined the spatial extent of the different fuel types and residential structures in the study area using photointerpretation procedures of large scale natural color orthophotographs. The results included simulated spatially explicit fire risk components along with wildfire risk exposure analysis and the expected net value change. Statistical significance differences in simulation outputs between the scenarios were obtained using Tukey’s significance test. The results of this study provide valuable information for decision support systems for short-term predictions of wildfire risk potential and inform wildland fire management of typical WUI areas in Greece. © 2014, Springer Science+Business Media New York