Development and Optimisation of the GM Oilseed Rape Event-Specific Pre-Spotted Plate (OSR-PSP) EURL-SP-07/16

This report describes the development of the "GM oilseed rape event-specific pre-spotted plates (OSR-PSP)" as a ready-to-use tool for GMO detection and identification. The OSR-PSP allows the detection of all GM oilseed rape events listed in the EU register of authorised GM events as of February 2017 and one not authorised event. The plate includes a total of 12 assays, consisting of 11 event-specific assays and one taxon-specific assay selected from those validated and approved by the EU Reference Laboratory for GM Food and Feed (EURL GMFF). The reaction conditions were standardised and the performance of the assays, in terms of specificity and sensitivity, were re-assessed in a single-laboratory study. The results confirm that the assays, under the new reaction conditions, fulfil the EU requirements for GMO testing and can be used for the detection of single and stacked oilseed rape GM events in food and feed samples.JRC.F.5-Food and Feed Complianc

The Translational Status of Cancer Liquid Biopsies

Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient’s body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay Summary: Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient’s body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research

Pan-cancer analysis of the metabolic reaction network

Metabolic reprogramming is considered a hallmark of malignant transformation. However, it is not clear whether the network of metabolic reactions expressed by cancers of different origin differ from each other or from normal human tissues. In this study, we reconstructed functional and connected genome-scale metabolic models for 917 primary tumor samples across 13 types based on the probability of expression for 3765 reference metabolic genes in the sample. This network-centric approach revealed that tumor metabolic networks are largely similar in terms of accounted reactions, despite diversity in the expression of the associated genes. On average, each network contained 4721 reactions, of which 74% were core reactions (present in >95% of all models). Whilst 99.3% of the core reactions were classified as housekeeping also in normal tissues, we identified reactions catalyzed by ARG2, RHAG, SLC6 and SLC16 family gene members, and PTGS1 and PTGS2 as core exclusively in cancer. These findings were subsequently replicated in an independent validation set of 3388 genome-scale metabolic models. The remaining 26% of the reactions were contextual reactions. Their inclusion was dependent in one case (GLS2) on the absence of TP53 mutations and in 94.6% of cases on differences in cancer types. This dependency largely resembled differences in expression patterns in the corresponding normal tissues, with some exceptions like the presence of the NANP-encoded reaction in tumors not from the female reproductive system or of the SLC5A9-encoded reaction in kidney-pancreatic-colorectal tumors. In conclusion, tumors expressed a metabolic network virtually overlapping the matched normal tissues, raising the possibility that metabolic reprogramming simply reflects cancer cell plasticity to adapt to varying conditions thanks to redundancy and complexity of the underlying metabolic networks. At the same time, the here uncovered exceptions represent a resource to identify selective liabilities of tumor metabolism

Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome

Protein secretory pathway in eukaryal cells is responsible for delivering functional secretory proteins. The dysfunction of this pathway causes a range of important human diseases from congenital disorders to cancer. Despite the piled-up knowledge on the molecular biology and biochemistry level, the tissue-specific expression of the secretory pathway genes has not been analyzed on the transcriptome level. Based on the recent RNA-sequencing studies, the largest fraction of tissue-specific transcriptome encodes for the secretome (secretory proteins). Here, the question arises that if the expression levels of the secretory pathway genes have a tissue-specific tuning. In this study, we tackled this question by performing a meta-analysis of the recently published transcriptome data on human tissues. As a result, we detected 68 as called “extreme genes” which show an unusual expression pattern in specific gene families of the secretory pathway. We also inspected the potential functional link between detected extreme genes and the corresponding tissues enriched secretome. As a result, the detected extreme genes showed correlation with the enrichment of the nature and number of specific post-translational modifications in each tissue’s secretome. Our findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined gene families to support the diversity of secreted proteins and their modifications

Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

The prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic targeted therapy. However, it is still unclear which biological processes underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans aggregated into diagnostic scores correlated with ccRCC prognosis.Thirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous (Low vs. High) or a continuous variable in a multivariate survival analysis.The survival difference between High vs. Low-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3% vs. 100%, p = 310-4 and 2-year OS rate = 73.3% vs. 100%, p = 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60% vs. 84%, p = 0.0591 and 2-year OS rate = 66.7% vs. 90%, p = 0.0206). In multivariate analysis, the urine biomarker score was an independent predictor of PFS (HR: 4.62, 95% CI: 1.66 to 12.83, p = 0.003) and OS (HR: 10.13, 95% CI: 1.80 to 57.04, p = 0.009).This is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted

Evidenze empiriche dalla volatilità dei prezzi elettrici durante la crisi energetica californiana. Cattura del regolatore nel caso Enron?

This work analyzes the trade data of the three major hubs of the Western US electricity markets – SP-15, Palo Verde, and Mid-C -, proposing the reconstruction and the organization of a new complete dataset of the daily time series of the electricity prices for the years 2001-2017. They are examined Enron operations and the main regulations and policy measures adopted in the American financial markets, before, during, and after the California crisis of 2000-2001, through a normative and a statistical analysis of the electricity prices. The objectives are to verify the existence of a relationship amongst price volatility and manipulative phenomena, and to test the effectiveness of the regulative policies applied. The results suggest a significant role played by Enron operations in the increase of the episodes and intensity of the volatility of the electricity prices in California and validate the hypothesis of a regulator capture. Questo lavoro analizza i trade data dei tre hubs principali dei mercati elettrici occidentali USA – SP-15, Palo Verde e Mid-C –, proponendo la costruzione e l’organizzazione di un nuovo dataset completo delle serie temporali giornaliere dei prezzi elettrici per gli anni 2001-2017. Si esaminano le operazioni Enron e le principali regolamentazioni e misure di policy adottate nei mercati finanziari americani prima, durante e dopo la crisi californiana del 2000-2001, attraverso un’analisi normativa e statistica dei prezzi elettrici. Gli obiettivi sono di verificare l’esistenza di una relazione tra volatilità dei prezzi e fenomeni manipolativi, e testare l’efficacia delle politiche regolative applicate. I risultati suggeriscono un ruolo significativo delle operazioni Enron nell’aumento di episodi e dell’intensità della volatilità dei prezzi elettrici in California e avvalorano l’ipotesi di una cattura del regolatore

Energy vulnerability around the world: The global energy vulnerability index (GEVI)

Vulnerability has garnered an increasing attention from academia, international community and industry. Nonetheless, formal definition, mainstreaming, and measurement of vulnerability are still flawed in the economic literature. Energy vulnerability, intended as the exposure of an energy system to adverse events and change, often overlaps with other energy policy concepts such as resilience, security, poverty, justice, and sustainability. This paper improves understanding of vulnerability in economics, energy, and sustainability studies by: i) constructing a dataset on energy vulnerability made of 180.000 observations; ii) formally defining energy vulnerability, while considering the regulatory framework and development agenda; iii) building a composite indicator on energy vulnerability; iv) analyzing and ranking the energy vulnerability of a vast number of OECD and non-OECD countries; v) testing for robustness checks. The analysis suggests that GDP is not necessarily a leading driver for energy vulnerability, whilst resource embedment is, since fossil and renewable energy producers are less vulnerable. Eventually, the paper validates that green countries are less vulnerable, differently from cold, heavily-industrialized, and highly-consuming countries

Checklist of the flora of the Monte Baldo (Italy)

Zweite Version einer Checkliste der Flora des Monte Baldo (Italien).Revisited and enlarged checklist of the flora of the Monte Baldo contains some 1100 taxa of vascular plants

Defining, measuring and ranking energy vulnerability

Vulnerability is reaching an increasing attention from both academia, international community and industry, being detected as a pillar of the development agenda. If the formal definition of overall vulnerability and resilience is still flawed in the economic literature, the measurement and mainstreaming of outlying characteristics and sound policies for energy vulnerability results almost uncovered, often overlapping with other energy issues. Energy vulnerability also results poorly enforced by regulatory, governmental, and legislative systems. After reviewing and furnishing a univocal ambient merging the multiple interpretations on such concepts, this work: i) defines energy vulnerability; ii) builds a composite indicator to measure energy vulnerability; and iii) analyzes and ranks OECD and non-OECD countries in terms of energy vulnerability. The regulatory framework, SDGs and the development agenda are examined, selected indicators from the WB’s WDI are analyzed. The indicator is weighted by a multivariate analysis and its robustness is checked through different techniques