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56 result(s) for "Gardiol, D"
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Human and primate tumour viruses use PDZ binding as an evolutionarily conserved mechanism of targeting cell polarity regulators
A unique feature of the cancer-causing mucosotropic human papillomaviruses (HPVs) is the ability of their E6 proteins to interact with a number of PDZ domain-containing cellular substrates, including the cell polarity regulators hDlg and hScrib. These interactions are essential for the ability of these viruses to induce malignant progression. Rhesus papillomaviruses (RhPV) are similar to their human counterparts in that they also cause anogenital malignancy in their host, the Rhesus Macaque. However, unlike HPV E6, the RhPV E6 has no PDZ-binding motif. We now show that such a motif is present on the RhPV E7 oncoprotein. This motif specifically confers PDZ-binding activity and directs the interaction of RhPV E7 with the cell polarity regulator Par3, which it targets for proteasome-mediated degradation. These results demonstrate an amazing evolutionary conservation of function between the RhPV and the HPV oncoproteins, where both target proteins of the same cell polarity control network, although through different components and pathways.
A case study of the May 30, 2017, Italian fireball
On May 30, 2017, at about 21 h 09 min 17 s UTC a green bright fireball crossed the sky of northeastern Italy. The fireball path was observed from some all-sky cameras starting from a mean altitude of 81.1 ± 0.2  km (Lat. 44 . 369 ∘ ± 0 . 002 ∘ N; Long. 11 . 859 ∘ ± 0 . 002 ∘ E) and extinct at 23.3 ± 0.2  km (Lat. 45 . 246 ∘ ± 0 . 002 ∘ N; Long. 12 . 046 ∘ ± 0 . 002 ∘ E), between the Italian cities of Venice and Padua. In this paper, on the basis of simple physical models, we will compute the atmospheric trajectory, analyze the meteoroid atmospheric dynamics, the dark flight phase (with the strewn field) and compute the best heliocentric orbit of the progenitor body. Search for meteorites on the ground has not produced any results so far.
Improvement of the extraction method of faint signals in γ -activity measurements of meteorites
. At the underground laboratory of Monte dei Cappuccini (OATo-INAF) in Torino (Italy) we set up selective HPGe-NaI(Tl) spectrometers for measurements of cosmogenic radioisotopes in meteorites in order to study centennial-scale modulation of solar activity. 44 Ti is a suitable proxy for this timescale, but its detection is difficult due to the strong interference by naturally occurring 214 Bi. In order to optimize the extraction of the 44 Ti signal, we have developed software procedures specifically designed to improve selectivity of the Ge-NaI detectors coincidence.
Developments and results in the context of the JEM-EUSO program obtained with the ESAF simulation and analysis framework
JEM-EUSO is an international program for the development of space-based Ultra-High Energy Cosmic Ray observatories. The program consists of a series of missions which are either under development or in the data analysis phase. All instruments are based on a wide-field-of-view telescope, which operates in the near-UV range, designed to detect the fluorescence light emitted by extensive air showers in the atmosphere. We describe the simulation software ESAF in the framework of the JEM-EUSO program and explain the physical assumptions used. We present here the implementation of the JEM-EUSO, POEMMA, K-EUSO, TUS, Mini-EUSO, EUSO-SPB1 and EUSO-TA configurations in ESAF. For the first time ESAF simulation outputs are compared with experimental data.
Role of a p53 polymorphism in the development of human papilloma-virus-associated cancer
The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.
Role of a p53 polymorphism in the development of human papillomavirus-associated cancer
The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.
The restoration of the quadrupole light bending
The ESA astrometric mission Gaia will be able to put to test General Relativity thanks to differential astrometric measurements. The differential experiment, GAREX, implemented in the form of repeated Eddington-like measurement, aims at measuring the quadrupole light bending due to an oblate planet by comparing the evolution of relative distances in stellar fields in the vicinity of it. Simulations which utilize (i) selected fields extracted from the GSCII data base, (ii) a realistic error model as function of the star's magnitude and distance from Jupiter's edge, show the real best scenarios and how to improve the Gaia ability to detect this relativistic effect.
Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation
Previous studies have shown that the oncogenic HPV E6 proteins form a complex with the human homologue of the Drosophila tumour suppressor protein, discs large (Dlg). This is mediated by the carboxy terminus of the E6 proteins and involves recognition of at least one PDZ domain of Dlg. This region of E6 is not conserved amongst E6 proteins from the low risk papillomavirus types and, hence, binding of HPV E6 proteins to Dlg correlates with the oncogenic potential of these viruses. We have performed studies to investigate the consequences of the interaction between E6 and Dlg. Mutational analysis of both the HPV18 E6 and Dlg proteins has further defined the regions of E6 and Dlg necessary for complex formation. Strikingly, co-expression of wild type HPV18 E6 with Dlg in vitro or in vivo results in a dramatic decrease in the amount of Dlg protein, whereas mutants of E6 which fail to complex with Dlg have minimal effect on Dlg protein levels. The oncogenic HPV16 E6 also decreased the Dlg levels, but this was not observed with the low risk HPV11 E6 protein. Moreover, a region within the first 544 amino acids of Dlg containing the three PDZ domains confers susceptibility to E6 mediated degradation. Finally, treatment of cells with a proteasome inhibitor overrides the capacity of E6 to degrade Dlg. These results demonstrate that Dlg is targeted by high risk HPV E6 proteins for proteasome mediated degradation.
Design of a compact astrometric instrument for the GAME mission
We present the design of a Fizeau interferometer to be implemented for the GAME mission. The aim is to measure the PPN γ parameter with the same technique used for the first time by Dyson, Eddington et al., but at a 10−6 accuracy level. GAME will observe about 106 sufficiently bright stars at about 2° from the Sun. A dedicated space mission has the advantage of observing the light bending without waiting for an eclipse.