1. Ge(2), Ge(1) and Ge-E´ centers in irradiated Ge-doped silicaLayla Martin-Samos, Nicolas Richard, Sylvain Girard, A. Boukenter, Youcef Ouerdane, Luigi Giacomazzi, 2015, izvirni znanstveni članek Najdeno v: ključnih besedah Povzetek najdenega: ...silica, density-functional theory, defects, ... Ključne besede: silica, density-functional theory, defects Objavljeno: 17.05.2016; Ogledov: 3340; Prenosov: 97
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2. MODIFIED U1 RNAs AS SPLICING CORRECTORS IN HUMAN GENETIC DISORDERSKatarzyna Rajkowska, 2018, doktorska disertacija Opis: The experimental work of this thesis was performed at the International Centre
for Genetic Engineering and Biotechnology (ICGEB) in the Human Molecular
Genetics Group, under the scientific direction of Prof. Franco Pagani. The project
was developed during the academic years 2014-2017.
Modified U1 RNAs, also named Exon Specific U1s (ExSpeU1s) represent a novel
class of small RNA-based molecules that correct exons splicing defects. To evaluate
their therapeutic potential focused on Familial Dysautonomia (FD), a rare autosomal
recessive disorder characterized by progressive degeneration of the sensory and
autonomic nervous system. More than 99% of patients are homozygous for the T to
C transition in position 6 of the IKBKAP intron 20 (c.2204+6T>C). This substitution
modifies the exon 20 5’ splice site (5’ss) inducing exon skipping in a tissue-specific
manner and reducing the total amount of IKAP protein. The molecular mechanisms
underlying the IKBKAP mis-splicing are not completely clear and there
are no effective treatments.
In this thesis, I investigated the therapeutic potential of ExSpeU1s and the role
of cis- and trans-acting factors that regulates IKBKAP splicing. Using a splicing
functional assay, I identified ExSpeU1s that bind to intron 20 sequences and rescue
the exon 20 skipping defect. Interestingly, their rescue activity was modulated
by several splicing factors and requires a critical exonic splicing enhancer element.
Transfection experiment showed the involvement of both enhancing (TIA1, PTBP1
and PTB4) and inhibitory (SRSF3, hnRNPA1, FOX and FUS) splicing factors
in IKBKAP splicing. To better evaluate the ExSpeU1s therapeutic efficacy,
I transduced FD patient’s fibroblasts with a lentiviral vector expressing the most
active ExSpeU1. This resulted in a complete rescue of the exon skipping defect and
improvement in IKAP protein expression. Most importantly, intraperitoneal delivery
of ExSpeU1s by AAV9 into a transgenic mouse model, that recapitulates
the tissue-specific mis-splicing seen in FD patients, corrected the aberrant splicing
patterns in several tissues increasing the amount of the corresponding IKAP protein.
All together, these results identify novel regulatory splicing factors involved in the
IKBKAP exon 20 regulation and provide the proof of principle that ExSpeU1s
delivered in vivo by AAV vectors represent a novel therapeutic strategy for FD. Najdeno v: ključnih besedah Povzetek najdenega: ...small RNA-based molecules that correct exons splicing defects. To evaluate
their therapeutic potential focused on Familial... Ključne besede: Familial Dysautonomia, IKBKAP, IKAP, splicing, splicing defects, ExSpeU1, U1 snRNA, mouse model, AAV Objavljeno: 26.03.2018; Ogledov: 3112; Prenosov: 88
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4. EPR parameters of E' centers in v-SiO2 from first-principles calculationsNicolas Richard, Sylvain Girard, Youcef Ouerdane, A. Boukenter, Layla Martin-Samos, Luigi Giacomazzi, 2014, izvirni znanstveni članek Najdeno v: ključnih besedah Povzetek najdenega: ...silica, paramagnetic defects, EPR, disordered semiconductors... Ključne besede: silica, paramagnetic defects, EPR, disordered semiconductors Objavljeno: 03.10.2018; Ogledov: 2639; Prenosov: 0
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5. Neutron irradiation effects on the structural properties of KU1, KS-4V and I301 silica glassesYoucef Ouerdane, A. Boukenter, A. Ibarra, Layla Martin-Samos, P. Martín, Nicolas Richard, Sylvain Girard, Luigi Giacomazzi, M. León, 2014, izvirni znanstveni članek Najdeno v: ključnih besedah Povzetek najdenega: ...silica, defects, optical fibers, hardening... Ključne besede: silica, defects, optical fibers, hardening Objavljeno: 03.10.2018; Ogledov: 2378; Prenosov: 0
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6. Coupled theoretical and experimental studies for the radiation hardening of silica-based optical fibersR. Boscaino, M. Cannas, Youcef Ouerdane, A. Boukenter, S. Agnello, P. Paillet, Antonino Alessi, C. Marcandella, Diego Di Francesca, Layla Martin-Samos, Luigi Giacomazzi, Sylvain Girard, Nicolas Richard, 2014, izvirni znanstveni članek Najdeno v: ključnih besedah Povzetek najdenega: ...silica, defects, optical fibers, hardening... Ključne besede: silica, defects, optical fibers, hardening Objavljeno: 03.10.2018; Ogledov: 2333; Prenosov: 0
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7. Paramagnetic centers in amorphous GeO2Nicolas Richard, Layla Martin-Samos, Luigi Giacomazzi, 2015, objavljeni znanstveni prispevek na konferenci Najdeno v: ključnih besedah Povzetek najdenega: ...germanium dioxide, defects, density-functional theory, EPR... Ključne besede: germanium dioxide, defects, density-functional theory, EPR Objavljeno: 03.10.2018; Ogledov: 2336; Prenosov: 0
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8. Radiation Effects on Optical Fibers and Fiber-Based SensorsNicolas Richard, Philippe Paillet, Youcef Ouerdane, A. Boukenter, Sylvain Girard, Layla Martin-Samos, Luigi Giacomazzi, Claude Marcandella, 2015, samostojni znanstveni sestavek ali poglavje v monografski publikaciji Najdeno v: ključnih besedah Povzetek najdenega: ...Optical Fibers, radiation-induced point defects, dosimetry, ab-initio... Ključne besede: Optical Fibers, radiation-induced point defects, dosimetry, ab-initio Objavljeno: 24.10.2018; Ogledov: 2393; Prenosov: 0
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9. Overview of radiation induced point defects in silica-based optical fibersBlaz Winkler, Imène Reghioua, Simonpietro Agnello, Marco Cannas, Philippe Paillet, Nicolas Richard, Adriana Morana, A. Boukenter, Youcef Ouerdane, Vincenzo De Michele, Antonino Alessi, Sylvain Girard, Layla Martin-Samos, Luigi Giacomazzi, Diego Di Francesca, Thierry Robin, 2019, pregledni znanstveni članek Najdeno v: ključnih besedah Ključne besede: optical fibers, point defects, radiation-induced attenuation, GLPC, NBOHC, STH, ODC, P-doping, Ge-doping, Al-doping Objavljeno: 09.05.2019; Ogledov: 2037; Prenosov: 0
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