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| 2. |
- Ageron, M., et al.
(författare)
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ANTARES : The first undersea neutrino telescope
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
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Tidskriftsartikel (refereegranskat)abstract
- The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given. (C) 2011 Elsevier B.V. All rights reserved.
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| 3. |
- Aguilar, J A, et al.
(författare)
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Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope
- 2005
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 555:1-2, s. 132-141
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Tidskriftsartikel (refereegranskat)abstract
- The ANTARES neutrino telescope, to be immersed depth in the Mediterranean Sea, will consist of a three-dimensional matrix of 900 large area photomultiplier tubes housed in pressure-resistant glass spheres. The selection of the optimal photomultiplier was a critical step for the project and required an intensive phase of tests and developments carried out in close collaboration with the main manufacturers worldwide. This paper provides an overview of the tests performed by the collaboration and describes in detail the features of the photomultiplier tube chosen for ANTARES. (c) 2005 Elsevier B.V. All rights reserved.
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| 8. |
- De Palma, FDE, et al.
(författare)
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The Multifaceted Roles of MicroRNAs in Cystic Fibrosis
- 2020
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Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is a lifelong disorder affecting 1 in 3500 live births worldwide. It is a monogenetic autosomal recessive disease caused by loss-of-function mutations in the gene encoding the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR), the impairment of which leads to ionic disequilibria in exocrine organs. This translates into a chronic multisystemic disease characterized by airway obstruction, respiratory infections, and pancreatic insufficiency as well as hepatobiliary and gastrointestinal dysfunction. Molecular characterization of the mutational heterogeneity of CFTR (affected by more than 2000 variants) improved the understanding and management of CF. However, these CFTR variants are linked to different clinical manifestations and phenotypes, and they affect response to treatments. Expanding evidence suggests that multisystemic disease affects CF pathology via impairing either CFTR or proteins regulated by CFTR. Thus, altering the expression of miRNAs in vivo could constitute an appealing strategy for developing new CF therapies. In this review, we will first describe the pathophysiology and clinical management of CF. Then, we will summarize the current knowledge on altered miRNAs in CF patients, with a focus on the miRNAs involved in the deregulation of CFTR and in the modulation of inflammation. We will highlight recent findings on the potential utility of measuring circulating miRNAs in CF as diagnostic, prognostic, and predictive biomarkers. Finally, we will provide an overview on potential miRNA-based therapeutic approaches.
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| 9. |
- Ferrari, E, et al.
(författare)
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Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation
- 2017
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 8:1, s. e2544-
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF), the most common lethal monogenic disease in Caucasians, is characterized by recurrent bacterial infections and colonization, mainly by Pseudomonas aeruginosa, resulting in unresolved airway inflammation. CF is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel in epithelial cells, macrophages, and other cell types. Impaired bacterial handling by macrophages is a feature of CF airways, although it is still debated how defective CFTR impairs bacterial killing. Recent evidence indicates that a defective autophagy in CF macrophages leads to alterations of bacterial clearance upon infection. Here we use bone marrow-derived macrophages from transgenic mice to provide the genetic proof that defective CFTR compromises both uptake and clearance of internalized Pseudomonas aeruginosa. We demonstrate that the proteostasis regulator cysteamine, which rescues the function of the most common F508del-CFTR mutant and hence reduces lung inflammation in CF patients, can also repair the defects of CF macrophages, thus restoring both bacterial internalization and clearance through a process that involves upregulation of the pro-autophagic protein Beclin 1 and re-establishment of the autophagic pathway. Altogether these results indicate that cysteamine restores the function of several distinct cell types, including that of macrophages, which might contribute to its beneficial effects on CF.
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| 10. |
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| 11. |
- Maiuri, L, et al.
(författare)
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Defective proteostasis in celiac disease as a new therapeutic target
- 2019
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 10:2, s. 114-
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is a disease caused by loss-of-function mutations affecting the CF transmembrane conductance regulator (CFTR), a chloride channel. Recent evidence indicates that CFTR is inhibited by a gluten/gliadin-derived peptide (P31-43), causing an acquired state of CFTR inhibition within the gut that contributes to the pathogenesis of celiac disease (CD). Of note, CFTR inhibition does not only cause intra- and extracellular ion imbalances but also affects proteostasis by activating transglutaminase-2 (TGM2) and by disabling autophagy. These three phenomena (CFTR inhibition, TGM2 activation, and autophagy impairment) engage in multiple self-amplifying circuitries, thus forming an “infernal trio”. The trio hinders enterocytes from returning to homeostasis and instead locks them in an irreversible pro-inflammatory state that ultimately facilitates T lymphocyte-mediated immune responses against another gluten/gliadin-derived peptide (P57–68), which,upon deamidation by activated TGM2, becomes fully antigenic. Hence, the pathogenic protein gliadin exemplifies a food constituent the exceptional immunogenicity of which arises from a combination of antigenicity (conferred by deaminated P57–68) and adjuvanticity (conferred by P31-43). CF can be treated by agents targeting the “infernal trio” including CFTR potentiators, TGM2 inhibitors, and autophagy enhancers. We speculate that such agents may also be used for CD therapy and indeed could constitute close-to-etiological treatments of this enteropathy.
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| 14. |
- Piras, P., et al.
(författare)
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Evolution of the sabertooth mandible: A deadly ecomorphological specialization
- 2018
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Ingår i: Palaeogeography Palaeoclimatology Palaeoecology. - : Elsevier BV. - 0031-0182. ; 496, s. 166-174
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Tidskriftsartikel (refereegranskat)abstract
- Saber-toothed cats were armed with formidable weapons. They evolved a number of highly derived morphological features, most notably a pair of extremely long upper canines, which makes them unique within the felid family. Although the sabertooth character evolved several times among carnivorous mammals, sabertooth clades mostly had disjunctive occurrences both in space and time, and no sabertooth is alive today. We studied the rates of phenotypic and taxonomic diversification in the mandible of sabertooths, as compared to the rates calculated for both extinct and extant conical toothed cats. We found that the mandible's shape and physical properties in sabertooth clades evolved at distinctly higher rates than the rest of the felid tree. In addition, sabertooths had similar speciation rate to conical toothed cats, but statistically higher extinction rate. The wealth of morphological specializations required to be a sabertooth, and their tendency to focus on large-sized species as prey, was likely responsible for such high extinction rate, and for the peculiar, disjunctive patterns of sabertooth Glade occurrence in the fossil record.
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| 15. |
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| 16. |
- Villella, VR, et al.
(författare)
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Autophagy suppresses the pathogenic immune response to dietary antigens in cystic fibrosis
- 2019
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 10:4, s. 258-
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Tidskriftsartikel (refereegranskat)abstract
- Under physiological conditions, a finely tuned system of cellular adaptation allows the intestinal mucosa to maintain the gut barrier function while avoiding excessive immune responses to non-self-antigens from dietary origin or from commensal microbes. This homeostatic function is compromised in cystic fibrosis (CF) due to loss-of-function mutations in the CF transmembrane conductance regulator (CFTR). Recently, we reported that mice bearing defective CFTR are abnormally susceptible to a celiac disease-like enteropathy, in thus far that oral challenge with the gluten derivative gliadin elicits an inflammatory response. However, the mechanisms through which CFTR malfunction drives such an exaggerated response to dietary protein remains elusive. Here we demonstrate that the proteostasis regulator/transglutaminase 2 (TGM2) inhibitor cysteamine restores reduced Beclin 1 (BECN1) protein levels in mice bearing cysteamine-rescuable F508del-CFTR mutant, either in homozygosis or in compound heterozygosis with a null allele, but not in knock-out CFTR mice. When cysteamine restored BECN1 expression, autophagy was increased and gliadin-induced inflammation was reduced. The beneficial effects of cysteamine on F508del-CFTR mice were lost when these mice were backcrossed into a Becn1 haploinsufficient/autophagy-deficient background. Conversely, the transfection-enforced expression of BECN1 in human intestinal epithelial Caco-2 cells mitigated the pro-inflammatory cellular stress response elicited by the gliadin-derived P31–43 peptide. In conclusion, our data provide the proof-of-concept that autophagy stimulation may mitigate the intestinal malfunction of CF patients.
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