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

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

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

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

Elevation-layered dendroclimatic signal in eastern Mediterranean tree rings

Networks of tree-ring data are commonly applied in statistical reconstruction of spatial fields of climate variables. The importance of elevation to the climatic interpretation of tree-ring networks is addressed using 281 station precipitation records, and a network of 79 tree-ring chronologies from different species and a range of elevations in the eastern Mediterranean. Cluster analysis of chronologies identifies 6 tree-ring groups, delineated principally by site elevation. Correlation analysis suggests several of the clusters are linked to homogenous elevational moisture regimes. Results imply that climate stations close to the elevations of the tree-ring sites are essential for assessing the seasonal climatic signal in tree-ring chronologies from this region. A broader implication is that the elevations of stations contributing to gridded climate networks should be considered in the design and interpretation of field reconstructions of climate from tree rings. Finally, results suggest elevation-stratified tree-ring networks as a strategy for seasonal climate reconstruction

Typology, structural characterization and sustainability of integrated broiler farming system in epirus, Greece

The aim of this study was the detailed characterization of the existing zootechnical and financial management applied in broiler poultry farms in the Region of Epirus, Greece. The current situation was captured through the formation of a typology on the structural characterization of broiler farming system. The variables were recorded based on data from a stratified random sample according to Neyman’s methodology of 110 poultry farms. In the typology, hierarchical cluster analysis was applied to identify differences between farms and to support most of this differentiation. Chebyshev distance was used to maximize the effect of the cluster elements distance, as well as Ward’s clustering method, which aims to achieve greater homogeneity within the clusters. Bonferroni multiple comparison tests were used to evaluate the differences. Four clusters of different farm types were identified from the hierarchical cluster analysis. In conclusion, the production system of broiler farms in Epirus is intensive, especially in large farms that have made significant investments in fixed capital and implement successful management. However, the poultry sector in Epirus has further margin for improvement in both its productivity and profitability. © 2021 by the authors. Licensee MDPI, Basel, Switzerland