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- Accomando, E., et al.
(författare)
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Physics with e + e - linear colliders
- 1998
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Ingår i: Physics Reports. - 0370-1573. ; 299:1, s. 1-78
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Tidskriftsartikel (refereegranskat)abstract
- The physics potential of e + e - linear colliders is summarized in this report. These machines are planned to operate in the first phase at a center-of-mass energy of 500 GeV, before being scaled up to about 1 TeV. In the second phase of the operation, a final energy of about 2 TeV is expected. The machines will allow us to perform precision tests of the heavy particles in the Standard Model, the top quark and the electroweak bosons. They are ideal facilities for exploring the properties of Higgs particles, in particular in the intermediate mass range. New vector bosons and novel matter particles in extended gauge theories can be searched for and studied thoroughly. The machines provide unique opportunities for the discovery of particles in supersymmetric extensions of the Standard Model, the spectrum of Higgs particles, the supersymmetric partners of the electroweak gauge and Higgs bosons, and of the matter particles. High precision analyses of their properties and interactions will allow for extrapolations to energy scales close to the Planck scale where gravity becomes significant. In alternative scenarios, i.e. compositeness models, novel matter particles and interactions can be discovered and investigated in the energy range above the existing colliders up to the TeV scale. Whatever scenario is realized in Nature, the discovery potential of e + e - linear colliders and the high precision with which the properties of particles and their interactions can be analyzed, define an exciting physics program complementary to hadron machines.
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- Gaglione, R., et al.
(författare)
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Insights into the anticancer properties of the first antimicrobial peptide from Archaea
- 2017
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - : Elsevier BV. - 1872-8006 .- 0304-4165. ; 1861:9, s. 2155-2164
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Tidskriftsartikel (refereegranskat)abstract
- Background: The peptide VLL-28, identified in the sequence of an archaeal protein, the transcription factor Stf76 from Sulfolobus islandicus, was previously identified and characterized as an antimicrobial peptide, possessing a broad-spectrum antibacterial activity. Methods: Through a combined approach of NMR and Circular Dichroism spectroscopy, Dynamic Light Scattering, confocal microscopy and cell viability assays, the interaction of VLL-28 with the membranes of both parental and malignant cell lines has been characterized and peptide mechanism of action has been studied. Results: It is here demonstrated that VLL-28 selectively exerts cytotoxic activity against murine and human tumor cells. By means of structural methodologies, VLL-28 interaction with the membranes has been proven and the binding residues have been identified. Confocal microscopy data show that VLL-28 is internalized only into tumor cells. Finally, it is shown that cell death is mainly caused by a time-dependent activation of apoptotic pathways. Conclusions: VLL-28, deriving from the archaeal kingdom, is here found to be endowed with selective cytotoxic activity towards both murine and human cancer cells and consequently can be classified as an ACP.
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- Brunk, Elizabeth, et al.
(författare)
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Recon3D enables a three-dimensional view of gene variation in human metabolism
- 2018
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 36:3, s. 272-281
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures. These data provide a unique resource for investigating molecular mechanisms of human metabolism. Recon3D is available at http://vmh.life.
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- Coenen-Stass, Anna M. L., et al.
(författare)
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Comprehensive RNA-Sequencing Analysis in Serum and Muscle Reveals Novel Small RNA Signatures with Biomarker Potential for DMD
- 2018
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Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier BV. - 2162-2531. ; 13, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their biological relevance is largely unknown. To investigate the relationship between intracellular and extracellular sRNA levels on a global scale, we performed sRNA sequencing in four muscle types and serum from wild-type, dystrophic mdx, and mdx mice in which dystrophin protein expression was restored by exon skipping. Differentially abundant sRNAs were identified in serum (mapping to miRNA, small nuclear RNA [snRNA], and PIWI-interacting RNA [piRNA] loci). One novel candidate biomarker, miR-483, was increased in both mdx serum and muscle, and also elevated in DMD patient sera. Dystrophin restoration induced global shifts in miRNA (including miR-483) and snRNA-fragment abundance toward wild-type levels. Specific serum piRNA-like sRNAs also responded to exon skipping therapy. Absolute miRNA expression in muscle was positively correlated with abundance in the circulation, although multiple highly expressed miRNAs in muscle were not elevated in mdx serum, suggesting that both passive and selective release mechanisms contribute to serum miRNA levels. In conclusion, this study has revealed new insights into the sRNA biology of dystrophin deficiency and identified novel DMD biomarkers.
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- D'Avanzo, F, et al.
(författare)
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Mucopolysaccharidoses Differential Diagnosis by Mass Spectrometry-Based Analysis of Urine Free Glycosaminoglycans-A Diagnostic Prediction Model
- 2023
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Impaired glycosaminoglycans (GAGs) catabolism may lead to a cluster of rare metabolic and genetic disorders called mucopolysaccharidoses (MPSs). Each subtype is caused by the deficiency of one of the lysosomal hydrolases normally degrading GAGs. Affected tissues accumulate undegraded GAGs in cell lysosomes and in the extracellular matrix, thus leading to the MPS complex clinical phenotype. Although each MPS may present with recognizable signs and symptoms, these may often overlap between subtypes, rendering the diagnosis difficult and delayed. Here, we performed an exploratory analysis to develop a model that predicts MPS subtypes based on UHPLC-MS/MS measurement of a urine free GAG profile (or GAGome). We analyzed the GAGome of 78 subjects (38 MPS, 37 healthy and 3 with other MPS symptom-overlapping disorders) using a standardized kit in a central-blinded laboratory. We observed several MPS subtype-specific GAGome changes. We developed a multivariable penalized Lasso logistic regression model that attained 91.2% balanced accuracy to distinguish MPS type II vs. III vs. any other subtype vs. not MPS, with sensitivity and specificity ranging from 73.3% to 91.7% and from 98.4% to 100%, depending on the predicted subtype. In conclusion, the urine GAGome was revealed to be useful in accurately discriminating the different MPS subtypes with a single UHPLC-MS/MS run and could serve as a reliable diagnostic test for a more rapid MPS biochemical diagnosis.
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