225 research outputs found
The Syntesis of zeolites from hydrothermal experiments on Sardinian Tertiary clinoptilolite-bearing ignibrites.
No full textRuolo delle alterazioni mitocondriali nel processo di morte cellulare in patologie neurodegenerative
No full textI processi di morte cellulare sono caratterizzati da profondi cambiamenti morfologico-funzionali delle diverse componenti cellulari. In queste condizioni i mitocondri vanno incontro ad una serie di evidenti alterazioni, tra le quali la perdita del potenziale di membrana mitocondriale (MMP) (Reed and Kroemer, 2000) può rappresentare sia un evento precoce dei processi di apoptosi sia un segnale associato all’autofagocitosi degli organelli stessi (Rodriguez-Enriquez et al., 2004).
Nel nostro gruppo è stato osservato che cellule di neuroblastoma umano (TGA) iper-esprimenti la Ttransglutaminasi di tipo 2 (TG2), presentavano alterazioni sia nell’ultrastuttura sia nella fisiologia dei mitocondri (Piacentini et al., 2002), tra cui una iperpolarizzazione costitutiva della membrana interna. Benché l’espressione della TG2 venga indotta durante i processi di morte cellulare per apoptosi, il ruolo di questo enzima nella cascata di eventi che inducono la cellula a morire, non è stata ancora completamente chiarito. Lo scopo di parte di questa tesi di dottorato è stato quello di verificare, a livello molecolare, quali fossero le modificazioni TG2-dipendenti dei mitocondri e le eventuali interazioni con proteine implicate nella regolazione della via mitocondriale dell’apoptosi.
L’analisi della sequenza primaria della TG2 ha portato all’identificazione di una regione con un’elevata omologia col dominio BH3 delle proteine della famiglia di Bcl-2, le quali controllano l’omeostasi mitocondriale e mediano il rilascio dei fattori pro- ed anti-apoptotici dai mitocondri. Il ruolo biologico di questo dominio della TG2 è stato studiato mediante l’utilizzo di peptidi in grado di penetrare la cellula e mimare l’azione del dominio stesso. Questa strategia ha rivelato come la TG2 sia in grado di interagire con Bax a livello mitocondriale e mediante questa interazione provocare la fuoriuscita del citocromo c dagli organelli. La prima parte dei risultati presentati in questa tesi, analizzano l’azione della TG2 e suggeriscono che essa possa essere un nuovo tipo di proteina “BH3-only” e le modalità della sua interazione e/o attivazione di Bax, la collocano esattamente tra le così dette “Bid-like proteins”. Queste proteine, tramite il loro dominio BH3, sono in grado di attivare in modo diretto Bax e sono potenzialmente in grado di regolare la funzionalità si altri membri della famiglia di Bcl-2.
Contestualmente, il nostro gruppo si è occupato dello studio del possibile coinvolgimento della TG2 come modulatore della morte cellulare nella corea di Huntington (HD), una patologia caratterizzata da notevoli disfunzioni mitocondriali. Malgrado l’iper-espressione della TG2 induca alterazioni mitocondriali e stress ossidativo favorendo la morte cellulare (Piacentini et al., 2002), l’incrocio di topi transgenici (HD) R6/1 con i topi knock out per la TG2, evidenzia una riduzione della morte cellulare, un significativo miglioramento della motilità degli animali ed una prolungata sopravvivenza (Mastroberardino et al., 2002). Questo effetto è comunque indipendente dalla capacità dell’attività transamidasica della TG2 a formare le caratteristiche inclusioni intranucleari osservate nella patologia (Bailey and Johnson, 2005). Nella corea di Huntington, la degenerazione cellulare sembra dipendere dall’acquisizione di funzione tossica da parte dell’huntingtina mutata e la perdita di funzione protettiva da parte della proteina normale. Entrambi questi eventi portano a numerose alterazioni cellulari, che coinvolgono anche i mitocondri. Tali alterazioni possono indurre morte cellulare, che può manifestarsi sia come apoptosi sia come autofagia.
La seconda parte di questa tesi riguarda lo studio dell’effetto delle alterazioni mitocondriali che si riscontrano in linfociti derivati da pazienti affetti da HD. I linfoblasti presentano alcune delle caratteristiche osservate nei neuroni HD, d'altra parte, non essendo interessati dal processo degenerativo, permettono sia un'analisi diretta degli effetti dell'htt mutata rispetto a quella wild-type sia l’effetto della mutazione in etero- ed omo-zigosi. Infatti, recenti evidenze, hanno evidenziato una più rapida progressione della malattia nei pazienti omozigoti (Squitieri et al., 2003) probabilmente imputabile alla presenza in doppia dose della proteina mutata ed alla totale mancanza del ruolo protettivo svolto dall'htt normale.
Nella seconda parte di questa tesi sono state analizzate le diverse vie di morte cellulare e le alterazioni mitocondriali attraverso uno studio comparativo tra eterozigoti e omozigoti. In entrambi i casi si osservano evidenti e significative alterazioni morfologico-funzionali dei mitocondri che correlano con il genotipo delle linee cellulari.Apoptosis and autophagy are cell death pathways characterised by great modification of the cell structure, among which morphological and functional alterations of mitochondria. The loss of mitochondrial membrane potential (MMP) (Reed and Kroemer, 2000) could be considered both an early event towards apoptosis or a signal associated with autophagy of the organelles (Rodriguez-Enriquez et al., 2004).
We previously observed that TG2 (Transglutaminase 2) over-expressing cells showed mitochondria that were greatly modified with respect to both their ultrastructure and physiology (Piacentini et al., 2002), with a constitutive hyperpolarization of the inner membrane. Even if TG2 expression is increased during apoptosis, the exact role of the enzyme in the cascade of events leading to cell death remain to be clarified. The first part of this thesis investigated, at a molecular level, the extension of TG2- mitochondrial modification as well as the possible interaction between TG2 and the proteins involved in the regulation of the mitochondrial pathway of apoptosis.
The analysis of the TG2 primary sequence lead to the identification of a region with high homology with the BH3 domain of Bcl-2 family, to which belongs pro- and anti-apoptotic proteins. The biological role of the TG2 domain has been studied by means of cell-permeable peptides, mimicking the domain sequence. This kind of approach allow us to characterise the effect of TG2 at mitochondrial level, where it interacts with Bax and causes cytochrome c release. The obtained results suggest that TG2 might be a new kind of BH3-only protein and its modality of interaction and/or activation of Bax, place it in the so called “Bid-like” proteins. These proteins, by means of their BH3 domain, are direct activators of Bax and potentially able to regulate others Bcl-2 family members.
At the same time our group had been studying the possible involvement of TG2 as a cell death modulator in Huntington’s disease (HD). In fact, it is known that over-expression of TG2 leads to cell death in human neuronal cells by inducing mitochondrial alterations and oxidative stress (Piacentini et al., 2002), but also by crossing HD R6/1 transgenic mice with TG2 knockout mice, a marked reduction in cell death is observed in R6/1, TG2 null when compared withR6/1 transgenic mice. The reduction in cell death is paralleled by a significant improvement in motor performances of R6/1, TG2 null versus R6/1 mice and extended survival (Mastroberardino et al., 2002). However this is independent from TG2 capability to make intranuclear inclusions by its cross-linking activity (Bailey and Johnson, 2005). The degenerative process of Huntington disease, relies both on the acquisition of toxic function by mutated huntingtin (htt) as well as on the loss of protection exerted by the wild type protein. Both these events lead to a lot of cellular alterations, which involve also mitochondria and they lead to cell death by apoptosis and/or autophagy. The second part of this thesis deal with the study of mitochondrial alterations observed in lymphocyte derived from HD patients. Lymphoblasts display some characteristics observed in HD neurons, otherwise, as they are not involved in neurodegenerative process, they allow a direct analysis of mutated htt effects in respect to the wild-type one as well as the effect of the mutation in hetero- and homo-zygosis. Recent evidences suggested that, the faster progression of the disease observed in homozygous patients, might be due to the presence in double dose of the mutated protein, coupled to the complete loss of the wild type one’s protective role (Squitieri et al., 2003).
The second part of this thesis analyzes the different cell death pathways and the mitochondrial alterations in HD cell lines, through comparative study between heterozygous and homozygous patients. The results obtained show that in both cases we can observe plain and remarkable morfologial-functional alterations of mitochondria that correlates with the genotype of the patient
The Syntesis of zeolites from hydrothermal experiments on Sardinian Tertiary clinoptilolite-bearing ignibrites.
No full text
EPMA, SIMS and FTIR investigations on sodalites and haüynes from Somma-Vesuvius volcano (southern Italy). 14th European workshop EMAS, Modern Developments and Applications in Microbeam Analysis
No full textSodalite-group minerals (sodalite, tugtupite and danalite subgroups) commonly occur in
alkaline igneous rocks, and in some hydrothermal and metamorphic rocks. These minerals
present a zeolite-like cubic structure and two structural cavities per unit cell. Cationic and
anionic contents of SSG are of interest for the study of magmatic systems; in particular, their
volatile components can be useful because they can provide key information on the genetic
environment, like degassing dynamics, fluids behaviour during hydrothermal processes and so
on [1-4]. Besides, SSG are very promising in different fields of material science, since their
(ultra)microporous structures show high flexibility and versatility in hosting tetrahedral cations
and variable channels/cavities components. Hence, they can be suitable as advanced materials
and behave as models for many technological and commercial applications [5, 6], for instance
separation processing (i.e. hydrogen from gaseous macromolecules). The present study is
focused on crystal-chemical characterization of cationic and anionic components of SSG
occurring in various igneous to metamorphic rocks and ejecta from the alkaline-potassic
Somma-Vesuvius volcano (southern Italy), as revealed by using combined microbeam
techniques, i.e., EPMA, SIMS and μ-FTIR. Previous studies on sodalite-group minerals by
means of EPMA, Raman, and LA-ICP-MS techniques focussed on halogen- (Cl, Br) and
S-contents [2, 3, 8]. To the authors’ knowledge no studies on volatiles in SSG have been
performed so far by integrated SIMS-FTIR investigations. Compared to bulk analyses, SIMS
and μ-FTIR methods are particularly pivotal to probe trace to ultra-trace contents, speciations
and orientations of an absorber across the samples [1, 7]. Our investigations show that the
studied SSG correspond to sodalite sensu stricto, nosean (sulfatic sodalite) and haüyne. SIMS
measurements on H, F and C (quantified as H2O, F and CO2, respectively) show contents:
0.02 - 5.0 wt% H2O, 0.01 - 0.14 wt% F, and 0.69 - 2.95 wt% CO2. Within the single crystals,
the F and CO2 concentrations are virtually homogeneous, whereas in terms of H2O, samples
can vary from homogenous to strongly heterogeneous. Single-crystal FTIR spectra of SSG can
be grouped into sodalites and sulphatic sodalites/haüynes, according to the occurrence of the
12CO2 absorption at 2340 cm-1 [1, 9]. The absorption due to H2O and/or OH groups occurs as a
very broad band extending from 3700 cm-1 to 3000 cm-1. In all samples FTIR data show the
presence of CO32-. μ-FTIR focal plane array imaging shows a very heterogeneous and
antithetical distribution of CO2 and especially of H2O according to the SIMS data.
[ 1] Bellatreccia F, Della Ventura G, Piccinini M, Cavallo A and Brilli M 2009 Min. Mag.
73 399-413
[ 2] Hettmann K, Wenzel T, Marks M and Markl G 2012 Am. Mineral. 97 1653-1661
[ 3] Hammerli J, Spandler C, Oliver N H S and Rusk B 2014 Metam. Geol. 32 93-112
[ 4] Wang L X, Marks M A W, Keller J and Markl G 2014 Chem. Geol. 380 133-144
[ 5] Ferraris G and Merlino S 2005 Rew. Min., Geoch. MSA 57 448 pp.
[ 6] Riley B J, Pierce D A, Frank S M, Matyáša J and Burns C A 2015 J. Nuclear Mat. 459
313–322
[ 7] Ottolini L and Le Fèvre B 2008 Microchim. Acta 161 329-336
[ 8] Hammerli J, Rusk B, Spandler C, Emsbo P and Oliver N H S 2013 Chem. Geol. 337-
338 75-87
[ 9] Balassone G, Bellatreccia F, Mormone A, Biagioni C, Pasero M, Petti C, Mondillo N and
Fameli G 2012 Mineral. Mag. 76 191-21
The Jabali nonsulfide Zn-Pb-Ag deposit, western Yemen
No full textThe Jabali Zn–Pb–Ag deposit is located about 110 km east of Sana'a, the capital of Yemen, along the western border of the Marib-Al-Jawf/Sab'atayn basin. The economic mineralization at Jabali is a nonsulfide deposit, consisting of 8.7 million tons at an average grade of 9.2% zinc, derived from the oxidation of primary sulfides. The rock hosting both primary and secondary ores is a strongly dolomitized carbonate platform limestone of the Jurassic Shuqra Formation (Amran Group). The primary sulfides consist of sphalerite, galena and pyrite/marcasite. Smithsonite is the most abundant economic mineral in the secondary deposit, and is associated with minor hydrozincite, hemimorphite, acanthite and greenockite. Smithsonite occurs as two main generations: smithsonite 1, which replaces both host dolomite and sphalerite, and smithsonite 2, occurring as concretions and vein fillings in the host rock. At the boundary between smithsonite 1 and host dolomite, the latter is widely replaced by broad, irregular bands of Zn-bearing dolomite, where Zn has substituted for Mg. The secondary mineralization evolved through different stages: 1) alteration of original sulfides (sphalerite, pyrite and galena), and release of metals in acid solutions; 2) alteration of dolomite host rock and formation of Zn-bearing dolomite; 3) partial dissolution of dolomite by metal-carrying acid fluids and replacement of dolomite and Zn-bearing dolomite by a first smithsonite phase (smithsonite 1). To this stage also belong the direct replacement of sphalerite and galena by secondary minerals (smithsonite and cerussite); 4) precipitation of a later smithsonite phase (smithsonite 2) in veins and cavities, together with Ag- and Cd-sulfides.
The δ18O composition of Jabali smithsonite is generally lower than in other known supergene smithsonites, whereas the carbon isotope composition is in the same range of the negative δ13C values recorded in most supergene nonsulfide ores. Considering that the groundwaters and paleo-groundwaters in this area of Yemen have negative δ18O values, it can be assumed that the Jabali smithsonite precipitated in different stages from a combination of fluids, possibly consisting of local groundwaters variably mixed with low-temperature hydrothermal waters. The carbon isotope composition is interpreted as a result of mixing between carbon from host rock carbonates and soil/atmospheric CO2.
The most favorable setting for the development of the Jabali secondary deposit could be placed in the early Miocene (~ 17 Ma), when supergene weathering was favored by major uplift and exhumation resulting from the main phase of Red Sea extension. Low-temperature hydrothermal fluids may have also circulated at the same time, through the magmatically-induced geothermal activity in the area
Fluorophlogopite and F-rich phases in limestone clasts from the Campanian Ignimbrite quarried at Fiano (southern Italy): mineralogical, geochemical and volcanological insights.
No full textFluorine-rich metamorphosed xenoliths associated to the distal Campanian Ignimbrite (CI) tephra (Campania region,
southern Italy) have long attracted the interest of the mineralogical community (i.e. Scacchi, 1890; Zambonini, 1919;
Masi & Turi, 1972; Balassone et al., 2002). These rocks derive from the Mesozoic carbonate lithotypes of the
Campanian Apennine, embedded in the pyroclastic flow and presently resting at the bottom of the tuff formations. The
sedimentary protoliths suffered from the action of hot, volatile-rich pyroclastic flow, and consequently were affected by
thermal metamorphism to various degrees. Their peculiarity is the occurrence of F- and Mg-bearing phases, with an
ubiquitous presence of neoformed fluorite. The occurrence at Fiano quarries (the so-called “Tufare”) is the classical
locality for these rock xenoliths. Similar rocks were also found in the CI of the Caserta area, and in the Latium region
(Colli Albani). This research aims both at a crystal chemical study of fluorophlogopite occurring in the Fiano xenoliths,
and at a geochemical and volcanological survey, to constrain the petrogenesis processes related to this rare F-, Mg-rich
assemblage and to CI.
The analysed samples belong to two lithotypes: mica-bearing clasts and variably metamorphosed carbonate blocks.
The former lithotype is represented by abundant fluorite, followed by fluorophogopite, F-rich chondrodite, fluoborite,
diopside and (Fe,Mg)-oxides. Minor to trace contents of calcite, humite, tremolite, and grossular also occur. Carbonate
rocks can show calcite only, or also trace amounts of fluorite. The Fiano micas composition approaches that of the
Vesuvius micas from the 1872 eruption (Balassone et al., 2013). The micas belong to the 1M polytype and have crystal
chemical features typical of fluorophlogopites i.e., low c lattice parameter (~ 10.13 Å), (~ 2.060 Å) and (~ 3.135 Å)
distances. New data on minor to ultratrace elements amounts found in the studied clasts, together with Carbon and
Oxygen isotope data will be reported and interpreted in a petrogenetic and volcanological frame.
Balassone G., Franco E., Mattia C.A., Petti C. & Puliti R. 2002. Re-examination of fluosiderite, an unknown mineral
from southern Italy: equal to fluorine-rich chondrodite. Eur. J. Min., 14, 151-155.
Balassone G., Scordari F., Lacalamita M., Schingaro E., Mormone A., Piochi M., Petti C. & Mondillo N. 2013.
Trioctahedral micas in xenolithic ejecta from recent volcanism of the Somma-Vesuvius (Italy): crystal chemistry and
genetic inferences. Lithos, 160-161, 84-97.
Masi U. & Turi B. 1972. Frazionamento isotopico del carbonio e dell'ossigeno negli inclusi calcarei metamorfosati del
"Tufo grigio campano" Auct. di Fiano (Salerno). Per. Min., 41, 291-310.
Scacchi A. 1890. La regione vulcanica fluorifera della Campania. Mem. R. Com. Geol. It., I, 1-48.
Zambonini F. 1919. Il tufo pipernoide della Campania e i suoi minerali. Mem. Descr. Carta Geol. It., 7, 130 pp
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