| 1. |
- Angiolini, Francesca, et al.
(författare)
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A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing
- 2019
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Ingår i: eLIFE. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-ΔTM. The latter exerts high angiogenic function through both autocrine and paracrine activities. Mechanistically, L1-ΔTM-induced angiogenesis requires fibroblast growth factor receptor-1 signaling, implying a crosstalk between the two molecules. NOVA2 and L1-ΔTM are overexpressed in the vasculature of ovarian cancer, where L1-ΔTM levels correlate with tumor vascularization, supporting the involvement of NOVA2-mediated L1-ΔTM production in tumor angiogenesis. Finally, high NOVA2 expression is associated with poor outcome in ovarian cancer patients. Our results point to L1-ΔTM as a novel, EC-derived angiogenic factor which may represent a target for innovative antiangiogenic therapies.
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| 2. |
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| 3. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 4. |
- De Chiara, Matteo, et al.
(författare)
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Domestication reprogrammed the budding yeast life cycle
- 2022
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X .- 2397-334X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Domestication of plants and animals is the foundation for feeding the world human population but can profoundly alter the biology of the domesticated species. Here we investigated the effect of domestication on one of our prime model organisms, the yeast Saccharomyces cerevisiae, at a species-wide level. We tracked the capacity for sexual and asexual reproduction and the chronological life span across a global collection of 1,011 genome-sequenced yeast isolates and found a remarkable dichotomy between domesticated and wild strains. Domestication had systematically enhanced fermentative and reduced respiratory asexual growth, altered the tolerance to many stresses and abolished or impaired the sexual life cycle. The chronological life span remained largely unaffected by domestication and was instead dictated by clade-specific evolution. We traced the genetic origins of the yeast domestication syndrome using genome-wide association analysis and genetic engineering and disclosed causative effects of aneuploidy, gene presence/absence variations, copy number variations and single-nucleotide polymorphisms. Overall, we propose domestication to be the most dramatic event in budding yeast evolution, raising questions about how much domestication has distorted our understanding of the natural biology of this key model species.
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| 5. |
- Moro, Giulia, et al.
(författare)
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Amino acid modified graphene oxide for the simultaneous capture and electrochemical detection of glyphosate
- 2024
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Ingår i: Materials Today Chemistry. - 2468-5194. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- Amino acid modified graphene oxide derivatives (GO-AA) are herein proposed as active materials for the capture and consequent electrochemical detection of organic pollutants in aqueous media. Glyphosate (GLY), an herbicide present in many water compartments, was chosen as benchmark species to test the effectiveness of these materials for its electroactive nature, allowing direct evidence of the capture event. L-Lysine, L-Arginine or L-Methionine were grafted on GO surface through epoxide ring opening reaction, promoting the amino acids binding and the concomitant partial reduction of GO. The synthetic process results in a charge resistance drop from 8.1 KΩ for GO to 0.8–2.1 KΩ for the various GO-AA, supporting the applicability of these materials in electrochemical sensing. The resulting GO-Lysine, GO-Arginine and GO-Methionine were exploited for GLY adsorption from water. GO-Lysine was found to have the strongest interaction with GLY, with a removal efficiency of 76 % after 1 h, which is about two-fold higher than those of granular activated carbon, the industrial benchmark adsorbent. GO-AAs outperform the pristine unmodified material also when exploited as active materials for the capturing and following electrochemical detection of GLY. GO-Lysine showed the best sensitivity and allowed the recognition of GLY in water even when present at concentration levels down to 2 μg/L. Molecular dynamics simulations confirmed that the enhanced performance of this material can be ascribed to the hydrogen bond and salt bridge interactions between Lys moieties and GLY, originated from hydrogen bond and salt bridge interactions.
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| 6. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 7. |
- Tellini, Nicolo, et al.
(författare)
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Ancient and recent origins of shared polymorphisms in yeast
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X. ; 8, s. 761-776
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Tidskriftsartikel (refereegranskat)abstract
- Shared genetic polymorphisms between populations and species can be ascribed to ancestral variation or to more recent gene flow. Here, we mapped shared polymorphisms in Saccharomyces cerevisiae and its sister species Saccharomyces paradoxus, which diverged 4-6 million years ago. We used a dense map of single-nucleotide diagnostic markers (mean distance 15.6 base pairs) in 1,673 sequenced S. cerevisiae isolates to catalogue 3,852 sequence blocks (>= 5 consecutive markers) introgressed from S. paradoxus, with most being recent and clade-specific. The highly diverged wild Chinese S. cerevisiae lineages were depleted of introgressed blocks but retained an excess of individual ancestral polymorphisms derived from incomplete lineage sorting, perhaps due to less dramatic population bottlenecks. In the non-Chinese S. cerevisiae lineages, we inferred major hybridization events and detected cases of overlapping introgressed blocks across distinct clades due to either shared histories or convergent evolution. We experimentally engineered, in otherwise isogenic backgrounds, the introgressed PAD1-FDC1 gene pair that independently arose in two S. cerevisiae clades and revealed that it increases resistance against diverse antifungal drugs. Overall, our study retraces the histories of divergence and secondary contacts across S. cerevisiae and S. paradoxus populations and unveils a functional outcome. Analysis of 1,673 sequenced Saccharomyces cerevisiae isolates identifies 3,852 sequence blocks introgressed from Saccharomyces paradoxus, most of which are recent and clade-specific. By contrast, divergent Chinese strains of S. cerevisiae show little evidence of introgression but do share ancient polymorphisms with S. paradoxus due to incomplete lineage sorting.
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| 8. |
- Amendoeira, Isabel, et al.
(författare)
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New digital confocal laser microscopy may boost real-time evaluation of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from solid pancreatic lesions: Data from an international multicenter study
- 2022
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Ingår i: EBioMedicine. - : ELSEVIER. - 2352-3964. ; 86
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Tidskriftsartikel (refereegranskat)abstract
- Background Pancreatic cancer is an aggressive malignancy and a leading cause of cancer death worldwide; its lethality is partly linked to the difficulty of early diagnosis. Modern devices for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) were recently developed to improve targeting and sampling of small lesions, but innovative technologies for microscopic assessment are still lacking. Ex vivo fluorescence confocal laser microscopy (FCM) is a new digital tool for real-time microscopic assessment of fresh unfixed biological specimens, avoiding conventional histological slide preparation and potentially being highly appealing for EUS-FNB specimens. Methods This study evaluated the possible role of FCM for immediate evaluation of pancreatic specimens from EUS-FNB. It involved comparison of the interobserver agreement between the new method and standard histological analysis during international multicenter sharing of digital images. Digital images from 25 cases of EUS-FNB obtained with real-time FCM technology and 25 paired digital whole-slide images from permanent conventional paraffin sections were observed by 10 pathologists from different Institutions in Europe, Japan, and the United States, in a blinded manner. The study evaluated 500 observations regarding adequacy, morphological clues, diagnostic categories, and final diagnosis. Findings Statistical analysis showed substantial equivalence in the interobserver agreement among pathologists using the two techniques. There was also good inter-test agreement in determining sample adequacy and when assigning a diagnostic category. Among morphological features, nuclear enlargement was the most reproducible clue, with very good inter-test agreement. Interpretation Findings in this study are from international multicenter digital sharing and are published here for the first time. Considering the advantages of FCM digital diagnostics in terms of reduced time and unaltered sample maintenance, the ex vivo confocal laser microscopy may effectively improve traditional EUS-FNB diagnostics, with significant implications for planning modern diagnostic workflow for pancreatic tumors. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 9. |
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| 10. |
- Bales, Chris, et al.
(författare)
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D2.1c Simulation Results of Reference Buildings
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is the third part of the deliverable D2.1, where the other two parts report on the energy consumption in the building stock in Europe based on the available energy statistics (D2.1a) and the energy policies related to buildings (D2.1b).The aim of this report is to give complementary information about the heating and cooling demands of residential and office buildings based on simulations, so that the many gaps in the energy statistics can be filled and the statistics can be critically evaluated. The methodology results in a complete and consistent overview of the heating and cooling demands in residential and office buildings for seven different climate regions covering the whole of the EU and six different periods of construction, covering pre-1945 to post 2000. In addition, the data for the residential building stock is split into single family houses, small and large multifamily houses, while for offices the results are given for low and high rise offices with 6 or 12 office units per floor.The simulation models have been benchmarked (calibrated) against the energy statistics for each of the seven climate regions based on the aggregated data for the whole residential building stock and then for the office building stock in that climate region (in D2.1a). The methodology derives the aggregated average using weighted averages of data split into periods of construction and typology for both energy statistics and simulation results. The weighting is done based on heated and cooled floor area. As nearly all of the energy statistics are given in terms of consumption, while simulation results were calculated as demand, the demand data were converted to consumption data. One fixed conversion factor was used for heating (average efficiency 0.8) and one for cooling (average EER 2.5). Since the calculated demands strongly depend on the imposed heating or cooling set temperatures, this simulation parameter was varied so that the aggregated simulation result was the same as that for the consumption derived from the energy statistics. The calibrated models were then used to derive the average heating and cooling consumptions of the building stock in the seven climate regions.The methodology has a number of uncertainties, both in terms of the energy statistics as well as in terms of the simplifications and assumptions in the simulation models. During the calibration process a number of inconsistencies have been detected for individual countries and climate regions between simulation results and energy use from statistic data. The mismatches are analytically assessed, showing improvements necessary both in terms of statistic data necessary for reliable energy estimations and data to be gathered in order to guarantee consistent simulations outcomes.Beside the building stock survey completion and statistic data quality assessment, the work is also the basis for the definition of suitable Energy Renovation Packages and Products within the iNSPiRe project. The simulation results will be used to identify which building typologies, periods of construction and climate region have the largest potential for impact on the European scenario. Such information will be used within the iNSPiRe project to define reference Target buildings, as virtual demonstration cases to prove the potential improvements and impacts following the renovation process of a given share of the European building stock.
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