Archivio Aperto di Ateneo
Not a member yet
5899 research outputs found
Sort by
Alterationi delle funzioni perossisomiali indotte dall’instabilità genomica e la loro rilevanza nell’invecchaimento
No full textPeroxisomes are single-membrane, multipurpose, cytoplasmic organelles
playing a crucial role in numerous anabolic and catabolic functions, mainly
related to lipid and reactive oxygen species (ROS) metabolism. Defects in
either their biogenesis or metabolic aspects result in severe developmental
disorders, involving multiple organs, markedly liver and brain. Peroxisomes
are remarkably heterogeneous in the different cell types and are capable of
modifying their own shape and functions, according to the cellular needs, to
meet prevailing environmental conditions. Because of their essential role in
cell homeostasis and preservation, peroxisomes' contribution to the ageing
process is receiving increasing attention. Indeed, it has been shown that in
normal ageing the inner organization of these organelles is compromised
and upset. In addition, when catalase activity is chronically reduced, cells
respond in a dramatic manner, displaying a cascade of accelerated ageing
reactions.
Ageing has been intrinsically associated with accumulation of
macromolecular damage, particularly in DNA. Consistently, defects in
DNA repair mechanisms result in accelerated ageing. Nucleotide excision
repair (NER) is a versatile pathway responsible for repairing helixdistorting
DNA lesions - including UV radiation-induced pyrimidine dimers
- chemical adducts, and oxidative lesions. NER progresses along two subpathways:
the global-genome NER (GG-NER) and the transcriptioncoupled
NER (TC-NER). GG-NER removes lesions genomewide, while
TC-NER repairs DNA damage that hampers the progression of the RNA
polymerase II complex (RNAPIIo) and therefore concerns transcriptionally
active genes. Both sub-pathways converge into a common mechanism that
involves DNA unwinding, lesion verification and dual incision, followed by
DNA re-synthesis and ligation.
Null and hypomorphic Ercc1 mutant mice display accelerated ageing
phenotype accurately recapitulating that observed in progeroid human
syndromes - which are caused by inherited defective NER - such as
xeroderma pigmentosum and Cockayne syndrome. Particularly, previous
investigations on hepatic tissue of Ercc1 mutant mice have revealed
alterations in the expression of peroxisome proliferator-activated receptor
(PPAR)-α and –γ. Changes in these genes, which are not only crucial
ii
regulators of peroxisomal biogenesis and function, but more generally of
cell metabolism, were framed in a context of bioenergetics.
Collectively, these findings emphasize the involvement of peroxisomes in
ageing processes and provided the rationale for my PhD project. This aimed
at exploring mutual relationship between peroxisomes and DNA damage,
clarifying whether: (i) genomic instability affects peroxisomal function
and/or biogenesis, and (ii) modulating peroxisomal function/biogenesis may
influence cellular response to exogenous genotoxic insult.
The first part of my PhD project focussed on possible peroxisomal
alterations in a progeroid condition generated by Ercc1 deficiency. To this
end, we performed molecular and morphological experiments in the liver
tissue of wild type and Ercc1Δ/- to evaluate the expression of peroxisomal
membrane and matrix markers.
Relevantly, several important pathways seem to be dysregulated, in
particular those related to ROS and lipid metabolism, and the variation of
specific peroxisomal proteins emphasized that some alterations actually
involved peroxisomes. Additionally, ultrastructural analyses highlighted
abnormalities in the cellular organization of mutants in respect to wild type,
especially concerning mitochondrial membrane system. This interesting
finding is in line with the compelling evidence establishing a close
evolutionary, functional, and biogenetic link between peroxisomes and
mitochondria.
Furthermore, peroxisomal changes were investigated even in the brain,
where the expression of peroxisomal proteins varies among specific
neuronal populations. Defective DNA repair was demonstrated to also
influence brain peroxisomes, in a non-linear fashion, since changes
observed in mild vs. severe mutants can consist in either induction or
repression of peroxisomal functions, also depending on the considered
cerebral area.
As a conclusion for this part of my work, we may assert that defects in NER
impact peroxisomal metabolism not only in the liver of mutants mice, but
even in their brain, where their importance is still dimly understood and that
we were able to shed light on the unexplored role of peroxisomes in
accelerated ageing process.
iii
The second part of the study further explored the link between DNA
damage accumulation and peroxisomes, shifting to cell models, including
human dermal fibroblasts (CHDF) and neuroblastoma cells (SH-SY5Y). In
view of a flipped experimental procedure, we have begun modulating the
dynamic feature of peroxisomes, by pre-treating cells with fenofibrate (FF),
a peroxisome proliferator mainly employed as a hypolipidemic drug.
Subsequently, cells underwent exogenous DNA injury (UVC radiation). FF
is able to influence the expression levels of peroxisomal proteins. This
effect was observed in all cell types considered, and generally dosedependent.
Interestingly, UV radiation enhances the response to the drug,
probably exacerbating microenvironmental stress conditions, which
promote cellular response to the damaging insult.
More specifically, FF impacts NER capacity of the cells modulating both
the unscheduled DNA synthesis (UDS) and transcription recovery.
Noteworthy, cells, because of the combination of a double induced-stress
condition, responded varying their own redox status according to the dose
of the drug administered.
Definitively, our data provide a consistent depiction of how treatment with
FF induces changes in damaged cells. Yet FF affects cellular metabolism
depending on cell type considered and dose administered. Particularly, in
non-neuronal, dividing, primary and secondary cells FF improves DNA
repair; conversely in differentiated post-mitotic neuronal cells (retinoic acid
treated SH-SY5Y) FF impairs DNA repair. The effect is dichotomous and
may, or may not, involve PPARα activation, thus further studies will
address the reasons of such differences.
In conclusion, data collected during my three-year PhD project strongly
argue for a reciprocal modulation of the organelles and DNA damage repair
mechanisms, particularly in accelerated ageing, either endogenously
generated, or exogenously produced. These findings, shedding new light
into the relationship linking cell senescence with peroxisomal functions and
biogenesis, open the way to future studies aiming at investigating potential
protective strategies against age-related processes
La rilevanza penale della tortura. Questioni tradizionali, istanze sovranazionali e prospettive di riforma
No full textLa presente tesi si volge ad analizzare il divieto di tortura in ambito internazionale, europeo e italiano. La tutela assicurata dal diritto internazionale si rivela in Italia, al cospetto della mancanza di una regolamentazione in ambito interno, completamente priva di efficacia.
Gli Stati aderenti alla Convenzione Europea dei Diritti dell’Uomo, in ragione della natura inderogabile e assoluta del divieto previsto nell’art. 3 di tale Convenzione, si devono impegnare a proteggere in modo effettivo l’integrità fisica e la dignità umana delle persone private della loro libertà nel loro territorio. Per tanto in caso di violazione del divieto suddetto, gli Stati aderenti hanno il dovere di procedere ad indagini ufficiali, adeguate e approfondite che consentano di identificare e di punire le persone responsabili di tortura.
Abbiamo riscontrato anche l’inadeguatezza delle carceri dove la tortura diventa, in sostanza, un dato di sistema collegato alla situazione disumana e degradante dei luoghi di detenzione: da qui l’ulteriore necessità di aggiungere nel nostro ordinamento la fattispecie di tortura. Per quanto riguarda le discipline ed istituzioni particolarmente rigide nei confronti dei detenuti (come ad esempio il regime di cui all’art. 41 bis o.p.,gli opg, l’ergastolo, ecc), riteniamo che essi violino il divieto di praticare la tortura cui siamo costituzionalmente ed internazionalmente vincolati
Primo rapporto sulla scelta dei comitati tecnici della "Università Nazionale Somala"
No full textRapporto presentato dal dott. Malesani alla Direzione Generale per la Cooperazione allo Sviluppo del Ministero degli Affari Esteri relativamente alla costituzione dei Comitati Tecnici delle diverse facoltà dell'Università Nazionale Somala nell'ambito dell'implementazione del progetto di cooperazione italo-somala.Warbixin uu dott. Malesani siiyay Xafiiska Guud ee Iskaashiga Horumarinta ee Wasaaradda Arrimaha Dibadda ee Talyaaniga, oo ku saabsan sida kulliyadaha kala duwan ee Jaamacadda Ummadda Soomaaliyeed loogu sameeyay guddi cilmiyeeddo, si loo hirgeliyo mashruuca iskaashiga Talyaani-Soomaali.Report presented by Dr. Malesani to the Directorate General for Development Cooperation of the Ministry of Foreign Affairs about the the formation of the Technical Committees of the various faculties of the Somali National University within the implementation of the Italian-Somali cooperation project.Documento messo a disposizione dal Dott. Malesani (archivio personale).Dr. Malesani ayaa dokumentigan ku deeqay xarunta cilmibaarista.Document provided by Dr. Malesani (personal archive)
Protocollo nel quadro della Convenzione italo-somala di Cooperazione Scientifica, Culturale e Tecnica
No full textDefinizione dell'accordo nel quadro della Convenzione italo-somala di Cooperazione Scientifica, Culturale e Tecnica di potenziamento del programma estendendolo alla ricerca scientifica.Qeexidda heshiiska dhex maray Talyaaniga iyo Soomaaliya, oo ku saabsan: iskaashiga cilmiyeed, dhaqameed iyo farsameed, si loo xoojiyo barnaamijka, isagoo lagu sii kordhinayo cilmibaarista.Within the framework of the Italian-Somali Scientific, Cultural and Technical Cooperation Agreement: finalization of the agreement of the enhancement program with the aim of extending it to scientific research
Mogadiscio - Panorama del Quartiere di Amarini
No full textImmagine tratta dal sito "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) e inclusa nell'Archivio Somalia con il consenso del curatore della collezione Rick Davies.Sawir laga soo qaatay mareegta "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/), waxaana lagu biiriyay Kaydka af Soomaaliga, kaddib markii oggolaasho laga helay qofka diyaariyay oo ah Rick Davies.Image taken from the website "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) and included in the Somali Archive with the permission of the owner of the collection, Mr. Davies
Bibliografia Ost-Afrika
No full textArchivio bibliografico e documentario relativo alla Somalia, curato dal Prof. Ernesto Milanese e contenente più di 9000 entrate bibliografiche.Kayd raadraac iyo dokumentooyin ku saabsaan Soomaaliya, waxaana soo diyaariyay Prof. Ernesto Milanese. In ka badan 9000 raadraaceed ayaa halkaas ku kaydsan.Biliographical and documentary archive about Somalia, edited by Prof. Ernesto Milanese and including more than 9000 bibliographical entries.Link: http://www.sba.unifi.it/CMpro-v-p-745.htm
Radio Mogadiscio: Radiodramma 2
No full textMasraxiyad raadiyeed oo laga soo daayay raadiyo Muqdisho 80meeyadii.Radiodramma mandato in onda da Radio Mogadiscio negli anni '80.Radio drama broadcast by Radio Mogadishu in the 80s
Mogadiscio - Viale Sorrentino
No full textImmagine tratta dal sito "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) e inclusa nell'Archivio Somalia con il consenso del curatore della collezione Rick Davies.Sawir laga soo qaatay "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) waxaa lagu biiriyay Kaydka Soomaaliyeed kaddib markii laga helay ruqsad milkiilaha xogururinta Rick Davies.Image taken from the website "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) and included in the Somali Archive with the permission of the owner of the collection, Mr. Davies
Somalia Ex Britannica
No full textImmagine tratta dal sito "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) e inclusa nell'Archivio Somalia con il consenso del curatore della collezione Rick Davies.Sawir laga soo qaatay "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) waxaa lagu biiriyay Kaydka Soomaaliyeed kaddib markii laga helay ruqsad milkiilaha xogururinta Rick Davies.Images from the past" (https://mogadishuimages.wordpress.com/) and included in the Somali Archive with the permission of the owner of the collection, Mr. Davies
Colonial period building on the lower Juba
No full textImage taken from the website "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) and included in the Somali Archive with the permission of the owner of the collection, Mr. Davies.Image taken from the website "Mogadishu: Sawirkan oo laga soo qaatay mareegta " (https://mogadishuimages.wordpress.com/) waxaa lagu biiriyay Kaydka Soomaaliyeed, kaddib markii laga helay ruqsad milkiilaha sawirkan, Mr. Davies.Immagine tratta dal sito "Mogadishu: Images from the past" (https://mogadishuimages.wordpress.com/) e inclusa nell'Archivio Somalia con il consenso del curatore della collezione Rick Davies