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Caratterizzazione strutturale e funzionale dei sistemi emoglobinici di due specie di pesci (Mugil cephalus e Ophisurus serpens) e di due varianti emoglobiniche umane (HbRoma e HbF-SS-Monserrato)
Get PDFThe hemoglobin is a very important protein that in vertebrates binds reversibly the oxygen and transport it to the tissue through the circulatory sistem. The aim of this study is to contribute to the knowledge of structural-functional relationship of the hemoglobin molecule through
structural and funcional characterisation of human hemoglobins natural variants and those present in different animal species. We report the identification and characterisation of two new hemoglobin variant, never described before, that we have named HbF-Monserrato-Sassari [Gγ93(F9) Cys Arg] and Hb Roma [β115(G17)Ala Val], and the hemoblobin systems of two species of fish, Mugil cephalus and Ophisurus serpens. HbF-Monserrato-Sassari [Gγ93(F9) Cys Arg] is an abnormal fetal hemoglobin observed in an apparently normal newborn baby during an hemoglobinopathies survey at birth in North Sardinian population. Sequencing of the γ globin genes revealed the TGT CGT transition at codon 93 in one of the two Gγ genes which causes the Arg for Cys amino acid replacement at position 93. The substitution was confirmed by mass spectrometric analysis which confirmed the presence of an additional Gγ chain whose mass value corresponds to the Arg Cys substitution already observed at the DNA level. Since modifications or substitutions at position β93 of HbA are known to affect the arrangement of a salt bridge at the α1β2 sliding contacts that are crucial for subunit cooperativity, the functional properties of the HbF-Monserrato-Sassari variant were analyzed to evaluate the effect of the substitution at the same position of the Gγ chain. The data indicate that substitution Cys Arg causes a significant increase in oxygen affinity and a slight decrease of both Bohr effect and cooperativity, with respect of normal HbF, indicating that Cys γ93 plays a key role for subunit cooperativity in the T R transition of the HbF tetramer. Since studies had shown that nitric oxide, the most important vasodilator agent, in the erytrocytes interacts in part with Cys β93 residues as S-nitrosohemoglobin (SNO-Hb), this variant, because of the loss of Cys γ93 residue, is considered to be potentially compromised in nitric oxide transport. Hb Roma [β115(G17)Ala Val] is an abnormal adult hemoglobin found in a 33- year-hold woman of Central Italian descent. We studied this previously uncharacterised variant because the β115(G17)Ala Val replacement occurs at the α1β1 (or α2β2) interface of the Hb molecule and then provides the opportunity to study how β115(G17)Ala Val substitution could perturb the hemoglobin structure and alter its function. Sequencing of the β-globin gene revealed the GCC GTC transition at codon 115 which causes the substitution of Ala, normally present at position β115, with Val. The substitution was confirmed by mass spectrometric analysis of the globins and tryptic peptides. The oxygen-binding properties, carried out on the mixture HbA/Hb Roma as the variant tetramer is undistinguishable by usual separation procedures, showed a significant increase in oxygen affinity with respect to normal HbA, both in the absence and
presence of 2,3- bisphosphoglycerate. With regard to the two species of fish, Mugil cephalus and Ophisurus serpens, it is known that among the vertebrates, fish display the most extensive presence of multiple Hb components, which show considerable differences in amino acid sequence. These structural differences are often responsible for different functional properties. In the case of Mugil cephalus structural and functional characterisations of its
hemoglobin system showed two major hemoglobins: HbI and HbII, which have the same functional properties, while hemoglobin system of O. serpens showed at least four anodic (isoelectric points, pI < 8) and one cathodic (pI > 8) components, which have different functional properties: the cathodic Hb may safeguard oxygen uptake under hypoxic and acidotic conditions, the anodic Hbs may be involved in pumping O2 in the swim bladder in order to maintain the neutral buoyancy of the fish. The natural hemoglobin variants are very important to evaluate how an amino acid
replacement could perturb the hemoglobin molecule and alter its function, whereas the comparative analysis between hemoglobins of different species allows to verify how this protein might have changed during evolution in relation with the different physiological and habitat needs
Metabolomic investigation of food matrices by ¹H NMR spectroscopy
Get PDFThe present Ph.D. work shows some applications on the NMR-based metabolomic approach in food science. The investigated food matrices are largely different, from a manufactured product that undergoes only physical treatments (bottarga), to a manufactured product where biochemical transformations take place (Fiore Sardo cheese), and, finally, a raw food (Argentina sphyraena). All of these food matrices were not chosen by chance, but they represent an important piece of economy of the island of Sardinia, or might be further valorized, gaining more importance in the near future. Indeed, bottarga and Fiore Sardo are typical products exported all over the world, while Argentina sphyraena is a fish a low economic interest, finding no appreciation, at the moment, on
the market. The results of this PhD study have contributed with new insights and deeper understanding of the potential perspective of the combined NMR/multivariate methods approach in food science, showing the great versatility of NMR spectroscopy and the strong synergetic relation between
NMR and chemometrics. NMR revealed its extraordinary potential, when applied to natural samples and products, while chemometric analytical technique proved to be an essential tool to get information on the properties of interest (e.g., geographical origin for bottarga) based on the knowledge of other properties easily obtained (i.e. NMR spectra). The investigation performed on bottarga demonstrated that a NMR-based metabolomics technique can be a powerful tool for the detection of novel biomarkers and establishing quality control parameters for bottarga. The work presented in this study evidenced the effectiveness of
metabolite fingerprinting as a tool to distinguish samples according both to the geographical origin of fish and the manufacturing process. The results relative to the Fiore Sardo showed the potential of the combination of NMR
spectroscopy and chemometrics as a promising partnership for detailed cheese analysis, providing knowledge that can facilitate better monitoring of the food production chain and create new opportunities for targeted strategies for processing. Such analysis may be performed in any stage
of the cheese manufacturing, allowing for thorough evaluation of every step in the process. Finally, the preliminary results relative to the metabolomic investigation of Argentina sphyraena should certainly serve as a basis for implement a research tool able to provide deeper insights on the biology of this fish species with all advantages offered by the metabolomics approach
Synthesis and anti-retroviral activity of novel 1,2-benzisothiazol-3(2H)-one benzenesulfonamides targeting the HIV nucleocapsid protein 7
Get PDFThe biological activity of new 1,2-benzisothiazol-3(2H)-one benzenesulfonamides is described. In cell-based assays the lead compound 6 inhibits multiplication, but not entry
into target cells, of HIV-1, HIV-2 and HIV-1 variants carrying clinically relevant mutations to non-nucleoside, nucleoside and protease inhibitors. In enzyme assays 6 fails to inhibit HIV-1 reverse transcriptase and integrase. Genome sequencing of HIV-1 mutants selected for resistance to 6 shows no mutations in both pol and env genes. On the contrary, two mutations map in the gag region coding for the nucleocapsid (NC) protein p7 (NCp7), which is involved in early and late key processes of retrovirus multiplication. Overall, the above results suggest that NCp7 is the target of title 1,2-benzisothiazol-3(2H)-
one benzenesulfonamides. Interestingly, 6 also shows concentration-dependent virucidal activity against cell-free HIV- 1 and HIV-2. Therefore, title compounds represent a new class of antiretroviral agents with
intriguing spectrum and mode of action
Valutazione ambientale strategica e governance territoriale: metodologie e procedure
Get PDFThe concepts of governance and sustainable development on which the thesis is based, are present in the literature with various meanings and are often misused in everyday language, so as to be regarded by many as words full of rhetoric, ambiguous, devoid of any real content, used to express everything and nothing. The likely cause of this misuse is that they are concepts related to complex
systems and processes, in terms of problems and implications, with a variety of people involved in different ways and whose number has increased over time.
While the concept of sustainability in the administration of the territory goes beyond the protection of the environment by including economic and social development as well as the environmental dimension, the analysis of the territorial governance processes requires the reconstruction of behaviour of the multiple participants, called stakehorders, which act in these processes.
An important governance tool, useful in guiding the plan of action to the paradigm of sustainable development, is the Strategic Environmental Assessment (SEA). Compared to its relationship with governance, the SEA could be defined as a set of rules, principles, techniques and tools with the
function of continually supporting the decision making process in order to generate consensus on actions to be taken and, above all, to ensure that such consent will last over time and become a network of stable relationships that can ensure continuity and consistency in the planning process. Governance, evaluation and planning are “inseparable concepts”, recalling Abdul Khakee’s article,
written in 1998. Using these considerations as a starting point, the aim of the thesis is to highlight, in terms of issues, the question of relationship between governance, planning and evaluation . At different levels of government (regional, provincial and local), through the analysis of case studies, the thesis identifies, in an original way, for territorial governance problems and possible solutions.
It define, in particular, procedural requirements for a SEA fully integrated in urban and territorial planning process with the creation of a procedural Protocol
Movements assessment and analysis for IMU based wearable networks
Get PDFMovements assessment and analysis based on Inertial Measurement Units (IMUs) is becoming a common feature for many kinds of applications, such as industrial, videogames, sports and medical. The approach predominantly used is the processing of sensors output as a waveform in which a pattern can be recognized or the initial and the final positions of the movement detected. Not only does this approach lack in precision of the measurement but also yields results that are not readily understandable, especially visually. On the other hand, visual interaction alone can be restricted by the difficulties in capturing some body positions and evaluating them.
Using six degrees of freedom IMUs and similarly to techniques that rely on optical devices, but obviously without employing them, we tried to view the sensors output as a representation of the movement in space, in order to obtain the actual trajectory of the whole movement. We also gave a suitable representation of the movements and efficient analysis and comparison techniques for evaluating them. In this thesis we will describe how our approach was realized, the experiments performed and the solutions proposed, even comparing them with other solutions proposed in literature.
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La valutazione e l’analisi di movimenti basata su dispositivi di misurazione inerziale (IMUs) sta diventando caratteristica comune in molti tipi di impieghi, come quelli industriali, video-ludici, sportivi e medici. L’approccio maggiormente utilizzato è il processamento dell’output dei sensori visto come una forma d’onda nella quale riconoscere un pattern o individuare le pose iniziali e finali del movimento. Questo approccio non solo è carente nella precisione della misurazione ma fornisce risultati di difficile lettura e comprensione, specialmente dal punto di vista visivo. D’altro canto la sola interazione visuale può essere limitata dalla difficoltà nel rilevare alcune posizioni del corpo e quindi valutarle.
Utilizzando IMUs a sei gradi di libertà e in maniera simile alle tecniche basate su dispositivi ottici, ma ovviamente senza impiegarli, abbiamo cercato di interpretate l’output dei sensori come rappresentazione del movimento nello spazio, al fine di ottenere la reale traiettoria dell’intero movimento. Inoltre, abbiamo fornito un’adeguata rappresentazione dei movimenti e efficienti tecniche per la loro analisi e il loro confronto. In questa tesi descriveremo come il nostro approccio è stato realizzato, gli esperimenti condotti e le soluzioni proposte, effettuando anche dei confronti con altre soluzioni proposte in letteratura
Extreme Events in Hydrology: an approach using Exploratory Statistics and the Generalized Pareto Distribution. Performances and properties of the GPD estimators with outliers and rounded-off datasets
Get PDFTwo large databases of daily cumulated rainfall are checked with the tools of the Exploratory statistics. The analysis allows to discover not common artefacts in the first database (rounding-off of data with different rounding-off rules) and several errors in the other one. The best statistical model to fit data is selected using the L-Moments ratio diagram as a tool to explore the accommodation of each dataset to other alternative
models. This tool suggests the Generalized Pareto Distribution as the best statistical model for this data, but the application of this distribution requires an estimate of the optimal threshold for each dataset. A detailed analysis of the present techniques for the
optimal threshold selection is performed and a new approach based on quantile sums is proposed. Furthermore the performances of the GPD parameters estimators are checked
for robustness against spurious rounded-off data and severe outliers
Measurement of strange hadron production and perspectives for the search of D⁰→ µ⁺µ⁻ decay at LHCb
Get PDFThe study of V⁰ particles in pp collisions is important for the comprehension of soft processes involved in strange quark production. Baryon asymmetry, measured as the ⊼/Λ production ratio, is crucial to understand the mechanism with which the baryon number information of the initial state is transported to the final state. Strange baryon over meson suppression, measured as the ⊼/K⁰s production ratio, is an important probe of the hadronisation mechanisms in high energy collisions.
In this dissertation we report measurements of ⊼/Λ and ⊼/K⁰s production ratios as obtained by the LHCb experiment in pp collisions at √s = 0.9 and 7 TeV.
Some theoretical aspects, the analysis procedure and results are presented and compared with phenomenological models using predictions based on Monte Carlo simulations.
We also present a measurement of the transverse polarisation of Λ baryons, which is important to understand the role of spin in high energy collisions.
Furthermore a preliminary outlook of the search of the very rare D⁰→ µ⁺µ⁻ decay is reported. This process involving flavour changing neutral currents is sensitive to contributions from different new physics scenarios. A selection for this decay and its possible background contributions are presented as obtained from the study of pp collisions at √s = 7 TeV. We present the results and discuss the prospects for the detection of this decay and the possibility to constraint the parameters of new physics scenarios.----------------------------
Lo studio di particelle V⁰ in collisioni pp è importante per la comprensione dei processi soffici coinvolti nella produzioni di quark strange.
L'asimmetria barionica, misurata come il rapporto di produzione ⊼/Λ, è cruciale per capire il meccanismo con cui l'informazione sul numero barionico è trasportata dallo stato iniziale a quello finale.
La soppressione dei barioni rispetto ai mesoni, misurata come il rapporto di produzione ⊼/K⁰s, è un'importante indicazione sui meccanismi di adronizzazione in collisioni ad alta energia.
In questa dissertazione riportiamo misure dei rapporti di produzione ⊼/Λ e ⊼/K⁰s ottenute dall'esperimento LHCb in collisioni pp a √s = 0.9 e 7 TeV.
Alcuni aspetti teorici, le procedure di analisi e i risultati sono presentati e confrontati a modelli fenomenologici usando predizioni basate su simulazioni Monte Carlo.
Presentiamo inoltre una misura della polarizzazione trasversa dei barioni Λ, importante per capire il ruolo degli effetti di spin in collisioni ad alta energia.
Infine riportiamo studi preliminari per la ricerca del decadimento estremamente raro D⁰→ µ⁺µ⁻. Questo processo, che coinvolge cambi di sapore in correnti neutre, è sensibile a contributi dovuti a scenari di nuova fisica. Vengono presentati una selezione per questo decadimento e il suo possibile fondo ottenuti dallo studio di collisioni pp a √s = 7 TeV. Presentiamo i risultati e discutiamo le prospettive per la rivelazione di questo decadimento e i possibili vincoli ponibili ai parametri degli scenari di nuova fisica
Forma urbana e architettura rurale di matrice gotico-catalana in Sardegna: l'esempio di Sanluri
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La separazione dalla prole reverte le modificazioni nell'espressione di BDNF, proteina Arc, spine dendritiche, LTP e neurogenesi osservate durante la gravidanza e dopo il parto
Get PDFLa gravidanza, il parto e il periodo post partum costituiscono particolari condizioni fisiologiche durante le quali il cervello femminile è sottoposto a modificazioni funzionali e morfologiche necessarie per l’insorgenza e il mantenimento del comportamento materno.
Il BDNF (Brain Derived Neurotrofic Factor), così come la proteina Arc (Activity-Regulated Cytoskeletal), costituisce un mediatore chiave della plasticità neuronale e la sua azione a lungo termine ha un ruolo importante nell’apprendimento, memoria, comportamento affettivo ed emozionale (1); entrambi inoltre sono in grado di regolare l’architettura neuronale (2).
Nel mio studio ho misurato le quantità di BDNF, di proteina Arc, la densità delle spine dendritiche (DSD), il potenziamento sinaptico a lungo termine (LTP) e la neurogenesi nell’ippocampo di femmine di ratto durante la gravidanza e dopo il parto. Inoltre ho valutato gli stessi parametri nelle madri private della prole una settimana dopo il parto.
Nel giro dentato i livelli di BDNF, Arc e DSD risultano essere aumentati al termine della gravidanza e durante l’allattamento, un effetto associato a un’incremento della LTP in confronto agli animali di controllo. La sottrazione della prole ha indotto una drastica riduzione dei livelli di BDNF, Arc e DSD, i cui valori sono scesi al di sotto dei livelli di controllo. Infine è stato osservato un incremento della neurogenesi al termine della gravidanza e in seguito alla sottrazione dei cuccioli e una riduzione durante l’allattamento.
La variazione dei livelli di espressione di BDNF e Arc, della DSD, i cambiamenti dell’LTP e della neurogenesi indotti dalla maternità e dalla separazione dei cuccioli possono avere un ruolo cruciale nella regolazione del comportamento materno.
------------------------------------------------------------------------------------------------------------------------Pregnancy, delivery and post partum period are among the most important physiological condition in which the brain of female undergo to the functional and morphological modification needed to adapt the behavior to the onset of motherhood.
Brain Derived Neurotrofic Factor (BDNF) is a key mediator of neuronal plasticity. Long term action of BDNF plays a key role in learning and memory, emotional and affective behaviour (1). Activity-regulated cytoskeleton-associated protein (Arc) also plays a relevant role in synaptic plasticity. A role for BDNF-Arc signalling in the regulation of neuronal architecture has been clearly demonstrated (2).
In my study the amount of BDNF, Arc protein, dendritic spines density (DSD), long term potentiation (LTP) and neurogenesis were measured in hippocampus of female rats during pregnancy and after delivery. The same parameters were also evaluated after delivery in the mothers deprived of their pups one week after birth.
In the dentate gyrus BDNF, Arc protein and DSD started to be markedly increased in the late pregnancy and during lactation, an effect associated to a significant increase of LTP and to a dramatic reduction of neurosteroid content compared to control rats. Separation of pups from their dams induced a marked reduction of DSD, BDNF and Arc protein, the amount of which felt at values markedly lower than control. Finally, we observed an increase of neurogenesis in the late pregnancy and after the separation of pups from their dams and a reduction during lactation.
The motherhood-induced change in the amount of DSD, BDNF, Arc, LTP and neurogenesis as well as the reversal by pups separation suggest a crucial role of neuronal plasticity in the regulation of maternal care. ---------------------------------------------------------------------------------------
1) Lu B. 2003, BDNF and activity-dependent synaptic modulation, Learn Mem.; 10(2):86-98.
2) Scharfman HE, Mercurio TC, Goodman JH, Wilson MA, MacLusky NJ 2003 Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor, J Neurosci.;23(37):11641-52