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Molecular characterization of a Mecp2Y120D mouse model and MeCP2 role in primary cilia formation: implications in Rett syndrome
No full textRett syndrome (RTT) is a neurological progressive disorder affecting about 1/10,000 new born females. Most cases of “classic” RTT are primarily ascribable to sporadic mutations in the X-linked MECP2 gene, encoding the multifunctional methyl-CpG-binding protein 2 (MeCP2). Studies of different mouse models of Mecp2 indicate that MeCP2 activities are modulated by a series of post-translational modifications.
We generated a knockin mouse model harboring the human pathogenic tyrosine 120aspartic acid (Y120D) mutation in Mecp2. This mutation was found in a female patient affected by RTT. Studies carried out on Mecp2Y120D mouse line showed a surprisingly severe phenotype overlapping that of Mecp2 null mice. The obtained data showed that the Y120D mutation causes a significant reduction in protein levels of Mecp2 and a clear defect in its chromatin binding. Since our studies on tyrosine 120 phosphorylation allowed us to functionally connect MeCP2 with the centrosome, we investigated whether Mecp2 deficiency might lead to centrosomal dysfunctions also in neurons that represent the most affected cells in RTT. Thus, we undertook a study to determine whether MeCP2 is required for the proper formation of the primary cilium. Our studies demonstrate that loss of MeCP2 determines a defect in ciliogenesis in all tested cells including murine neurons and astrocytes and RTT patients’ fibroblasts. We have also observed a functional defect in the activation of the Sonic Hedgehog pathway. Both morphological and functional defects are rescued by the stabilization of microtubules with an histone deacetylase 6 inhibitor
Atrofia Muscolare Spinale: presentazione clinica, quadri radiologici, nuovi trattamenti e biomarcatori
Full text linkSpinal Muscular Atrophy is an autosomal recessive disorder affecting 1:100,000 live births, in which survival motor neuron (SMN) protein deficiency leads to motor neuron degeneration and progressive muscle atrophy, weakness,and early mortality.
Most of SMA patients harbor homozygous SMN1 deletions while SMN2 copy number predicts the clinical subtype (SMA-I, -II, -III-IV). Few (3-5%) SMA patients display small mutations point mutations on the second allele. The behavior of point mutations in SMN1/SMN2 is heterogenous and requires proper validation.
In recent years the discovery of effective therapies has marked the history of Spinal Muscular Atrophy(SMA). The only currently approved drug is Nusinersen, which is an antisense oligonucleotide that binds to the SMN2 pre-mRNA downstream of exon 7,leading to the translation of a fully functional SMN protein. The treatment has opened up a new scenario with the creation of a new phenotypic spectrum.
We have studied prospectively patients treated with nusinersen, by planning serial evaluations : neurological exam, muscle strength (MRC), motor functional scales, timed tests, muscle MRI, CMAP and MUNE.
Monitoring long-term outcome measures will allow us to characterize the new phenotypes of the disease and to define the efficacy spectrum of Nusinersen in patients with different ages and degrees of motor impairment.
Neurofilament chains (Nf) are sensitive, liquor-based marker that can identify patients with neurodegenerative diseases, aid in the prediction of their long-term outcomes, and be used for assessing effects of treatment. At present, little is known about serum Nf levels in patients with SMA. To that purpose, we have measured the levels of Nf during the treatment with Nusinersen
Il corpo e l’immaginario politico nella società contemporanea
No full textThought, word, hermeneutics and imaginary - understood as a social product suspended between the spiritual/virtual and real/material dimensions - which we categorize as "performative saying", construct, influence and modify in the individual, social and therefore political sense, the life of bodies. There are different concepts of corporeity, because each society has its own performative saying, and what unites the performative saying of each society is precisely what binds it to the body, and the power of the performative saying lies in its imaginative dimension that produces real effect, effects that act on the body intended as the foundation of politics.
Considering that all social, economic, legal etc. practices are deeply influenced by the imaginary and performative saying that a society has about human body, the political meaning that this concept has in itself becomes clear: the scientific performative saying, the religious performative saying or the tribal one, ecc., determine the structures and the political organization of a society, in a continuous relationship of co-construction with the imaginary. Influencing and influenced by the complex network of relationships built through performative saying, the body is now more than ever a political saying itself, expression of the imaginary and therefore it is the field of experimentation and continuous changes
Effect of blueberry supplementation in overweight and obese pregnant women
Full text linkChildhood obesity is a serious problem growing worldwide that needs to be early considered and treated. Maternal overweight and obesity lead to foetal complications and to an increased risk of child obesity. Blueberry bio-active compounds have antioxidant properties and improve insulin sensitivity in obese individuals. We proposed a daily integration of a freeze-dried blueberry extract in the last trimester of a population of overweight and obese pregnant women. Mother cytokine milieu, birth weight and at age one, were compared with a matched control group.
Results: birth weight was significantly lower in those whose mothers assumed the blueberry extract (male: 3636 gr ± 56,7 in control group and 3302 gr ± 60,9 in the blueberry, P=.001; female: 3446 gr ± 53 in control group and 3094 gr ± 65,5 in the blueberry, P <.0001) and this result remained comparable at age one (male control group: 9597 gr ± 134,4; blueberry: 8656 gr ± 271,9; P=.0021; female control group: 8812 ± 167,5; blueberry: 8083 ± 266,3; P=.0211); pro-inflammatory cytokines (TNF-α and leptin) were significantly reduced in the blueberry group (control 29,89 pg/mL ± 0,283 vs blueberry 8,124 ng/mL ± 0,1085 and 17,28 ± 0,4742 vs 6,977 ± 0,1187, respectively); anti-inflammatory cytokines (TGF-β and IL-4) were significantly increased in the blueberry group (control 4,196 pg/ml ± 0,9752 vs blueberry 14,87 pg/ml ± 0,8844 and 14,87 pg/ml ± 0,8844 vs 55,22 ± 1,47, respectively), CRP levels were significantly lower in the blueberry group (control 5,917 mg/L ± 0,698 vs blueberry 3,741 mg/L ± 0,6279).
Conclusion: a daily dietary supplementation with bioactive from whole blueberries in overweight and/or obese pregnant women is an effective intervention to reduce the risk of foetal macrosomia and early childhood obesity
The prototype phase of the ENUBET positron tagger
Full text linkUnderstanding the interaction of neutrinos with the other particles of the Standard Model is a fundamental activity in particle physics.
The uncertainties on the initial neutrino flux limit the sensitivity on the neutrino cross section measurement in the GeV range to a precision of 10-20%.
The scientific goal of the ENUBET project is to improve this sensitivity up to 1% by developing an active decay tunnel, as opposed to traditional neutrino beams, which have a passive decay region.
By tagging the positrons emitted in the Ke3 decay (K+ -> π0 + e+ + νe) it is possible to infer the initial neutrino flux. If the tunnel is short enough (about 50 m) the Ke3 decay is the only source of neutrinos.
Shashlik calorimeters are suitable to instrument such a tunnel, because they are cost effective, have a good geometrical adaptability and their energy resolution can be tuned with the proper absorbing/scintillator tiles thickness and fiber frequency. To separate the positrons from the pion background these calorimeters are longitudinally segmented with a compact readout based on Silicon PhotoMultipliers embedded in the bulk of the calorimeter itself.
This thesis describes the prototyping activity of the ENUBET Collaboration for the positron tagger and the tests performed at the CERN PS-T9 beamline from July 2016 to October 2017. The details of each prototype design and the results in terms of linearity and energy resolution are presented
Physical Layer Identification and authentication of electronic devices
Full text linkIn this thesis, I have investigated the problem of identification and authentication of electronic devices through their physical layer intrinsic features or fingerprints. The concept is that small differences in the electronic components of electronic devices leave small but significant traces in the digital output generated by the electronic device. Then, an analysis of the digital output provides the capability to identify and/or authenticate an electronic device from its digital output with a degree of accuracy, which is based on various factors including environmental effects. This research area has become more prominent in recent times due to the increasing computing power available for signal processing and analysis, which allows a more efficient and accurate extraction of the fingerprints. Even if there is considerable research in this area, which has proven the concept both with theoretical analysis and experimental results, there are still many aspects to be investigated both for the different types of electronic devices and for the analysis of the digital output through signal processing and machine learning techniques. The PhD activities have investigated various novel aspects in comparison to the existing literature. This thesis describes most of the results and describes the novelty in comparison to previous research literature. Three specific use cases were considered: identification of wireless devices, microphones and magnetometers
Multimodal representation and learning
Full text linkRecent years have seen an explosion in multimodal data on the web. It is therefore important to perform multimodal learning to understand the web. However, it is challenging to join various modalities because each modality has a different representation and correlational structure. In addition, various modalities generally carry different kinds of information that may provide enrich understanding; for example, the visual signal of a flower may provide happiness; however, its scent might not be pleasant. Multimodal information may be useful to make an informed decision. Therefore, we focus on improving representations from individual modalities to enhance multimodal representation and learning. In this doctoral thesis, we presented techniques to enhance representations from individual and multiple modalities for multimodal applications including classification, cross-modal retrieval, matching and verification on various benchmark datasets
Enhancing data privacy and security related process through machine learning
Full text linkIn this thesis, we exploit the advantages of Machine learning (ML) in the domains of data security and data privacy. ML is one of the most exciting technologies being developed in the world today.
The major advantages of ML technology are its prediction capability and its ability to reduce the need for human activities to perform tasks. These benefits motivated us to exploit ML to improve users' data privacy and security. Firstly, we use ML technology to try to predict the best privacy settings for users, since ML has a strong prediction ability and the average user might find it difficult to properly set up privacy settings due to a lack of knowledge and subsequent lack of decision-making abilities regarding the privacy of their data. Besides, since the ML approach has the potential to considerably cut down on manual efforts by humans, our second task in this thesis is to exploit ML technology to redesign security mechanisms of social media environments that rely on human participation for providing such services. In particular, we use ML to train spam filters for identifying and removing violent, insulting, aggressive, and harassing content creators (a.k.a. spammers) from a social media platform. It helps to solve violent and aggressive issues that have been growing on social media environments. The experimental results show that our proposals are efficient and effective
Analogue Hawking radiation in Bose-Einstein condensates
Full text linkThis Thesis develops in the field of analogue gravity, a branch of physics which relies on a specific correspondence that exists between fluid dynamics and curved spacetimes; thanks to that, effects which are hard to study in the gravitational context are investigated in the realm of hydrodynamics with the hope that the consequent results could be transferred back to the cosmological domain and give us better insights in the gravitational context. In this Thesis, I try to introduce the reader to the realm of analogue gravity and to the concepts of Bose-Einstein condensation, Hawking radiation and its analogue counterpart (Chapter 1 and 2); then in Chapter 3 and 4 I describe the details of our work. In the past years, we have developed two directions of research, both aimed at the characterization of the analogue Hawking radiation in Bose-Einstein condensates. One side of our work had the purpose of investigating the results obtained in recent experiments apt to the detection of the analogue Hawking radiation in a quantum gas. Our results are very important in the description of the phenomena and give insights on how to develop future experiments (Chapter 3). The other side of our work aimed at the characterization of this effect from a theoretical point of view by means of an innovative approach, which allows for a much deeper and more detailed description of the radiation and helps shine new light on this effect (Chapter 4). In Chapter 5 we briefly discuss the possible developments of our studying, highlighting the missing pieces of this field and suggesting possible ways to approach the existing problems
Neutrino emission from Blazars.
Full text linkDuring the last decade, multi-messenger astronomy has become increasingly relevant for the astrophysical community. In this context the discovery of PeV neutrinos by IceCube in 2012, in clear excess to the expected atmospheric flux at very-high energy (≳ 100 TeV ), marked the beginning of the high-energy neutrino astrophysics era. Differently from photons, neutrinos can carry information about the core of the astrophysical objects that produce them, giving us a better understanding of the internal composition of their sources. The origin of these neutrinos is still an open issue. Among the possible extragalactic neutrino sources, Blazars start to stand out.
Blazars are associated to active galactic nuclei hosting a relativistic jet oriented close to our line of sight. The presence of jets and the strong non-thermal emission up to the TeV band makes them natural accelerators of particles. In September 2017 the spatial coincidence between a neutrino event detected by IceCube, with a good angular resolution, and a blazar, TXS 0506+056, was observed for the rst time. This event is even more intriguing because of the high-state emission in γ-ray band of this blazar. During the three years of my PhD, I focused my attention on the study of blazar objects as neutrino emitters. In this thesis all my work on this topic is presented