| 1. |
- Aguado, J, et al.
(författare)
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Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson-Gilford Progeria Syndrome
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4990-
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Tidskriftsartikel (refereegranskat)abstract
- Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo.
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| 2. |
- Carini, G., et al.
(författare)
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Thermally activated relaxations and vibrational anharmonicity in alkali-borate glasses: Brillouin scattering study
- 2008
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 78:2, s. 7-
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of Brillouin light scattering have been performed in (M2O)(0.14)(B2O3)(0.86) alkali-borate glasses, where M=Li and K, as a function of temperature between 15 and 300 K. The temperature behaviors of hypersonic attenuation and velocity have been explained in terms of thermally activated relaxations of intrinsic structural defects and of anharmonic interactions between hypersonic waves and thermal vibrational modes. In the temperature region above 150 K, where the mean free path of thermal modes is shorter than the acoustic wavelength, it has been shown that the sound propagation is mainly regulated by the Akhiezer mechanism of "phonon viscosity." It causes a linear increase in the hypersonic attenuation and a linear decrease in the sound velocity with increasing temperature.
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| 3. |
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| 4. |
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| 5. |
- Carini, Giovanni, et al.
(författare)
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Hypersonic attenuation in cesium borate glasses: Relaxation and anharmonicity
- 2009
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Ingår i: Materials Science & Engineering A: Structural Materials: Properties, Microstructure and Processing. - : Elsevier BV. - 0921-5093. ; 521-22, s. 247-250
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Konferensbidrag (refereegranskat)abstract
- The internal friction and the sound velocity in a cesium borate glass (Cs(2)O)(0.14)(B(2)O(3))(0.86) were measured at ultrasonic and hypersonic frequencies by Brillouin scattering measurements over the temperature range between 15 and 300 K. The analysis of the experimental results show that, in addition to thermally activated local motions of structural defects, the vibrational anharmonicity contributes substantially to the temperatures dependences of both the hypersonic loss and velocity. It has been also proved that above 150 K the vibrational anharmonicity appears to be governed by the Akhiezer mechanism of phonon viscosity.
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| 6. |
- Carini, Giovanni, et al.
(författare)
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Ultrasonic and hypersonic behaviours of borate glasses
- 2007
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Ingår i: Philosophical Magazine. - 1478-6435 .- 1478-6443. ; 87, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Comparative measurements of Brillouin light scattering and ultrasound in (K2O)0.04(B2O3)0.96 and (Ag2O)0.14(B2O3)0.86 borate glasses as a function of temperature between 1.5 and 300 K reveal that distinct mechanisms regulate the temperature behaviours of the acoustic attenuation. In the MHz range the attenuation and the sound velocity are mainly governed by (i) quantum-mechanical tunnelling below 20 K, (ii) thermally activated relaxations between 20 and 200 K and (iii) vibrational inharmonicity at even higher temperatures. In the GHz range and in the temperature interval between 77 and 300 K, additional contributions besides the relaxation process must be taken into consideration to account for the hypersonic attenuation.
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