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The hidden complexity of stellar population properties in high-Redshift early-type galaxies.
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Degeneration of the larval midgut of Bombix Mori during metamorphosis: role and regulation of autophagy and apoptosis.
No full textThe midgut of the silkworm, Bombyx mori, is extensively remodeled during metamorphosis: in fact, while cell death processes lead to the degeneration of the larval epithelium, the adult midgut is formed by the proliferation and differentiation of stem cells. Our group previously described the intervention of apoptotic and autophagic events in larval midgut cells undergoing degeneration (Franzetti et al., 2012). The present study aims at investigating the molecular pathways of apoptosis and autophagy, the role of the two processes and their relationship in this tissue.
We first analyzed the expression pattern of autophagic and apoptotic genes, as well as used specific markers to assess the precise timing of autophagy and apoptosis during metamorphosis. The results obtained confirm that autophagy is activated at spinning stage, while apoptosis intervenes with a delay of 24-48 hours. The final demise of apoptotic cells occurs by secondary necrosis and their content is released in the lumen of the adult midgut.
To investigate the mechanisms that lead to the activation of autophagy and apoptosis we used 20-hydroxyecdysone (20E), one of the main regulators of metamorphosis in insects. The administration of a single dose of 20E induces the transcription of both autophagic and apoptotic genes, but fully activates only autophagy. In contrast, the activation of effector caspases needs a second injection of 20E. These data suggest that, during development, autophagy is induced at the end of the last larval stage by the 20E commitment peak, while the onset of apoptosis occurs concomitantly with 20E metamorphic peak. Moreover, our results demonstrate that 20E activates autophagy by inhibiting the Tor pathway. However, inactivation of Torc1 through rapamycin administration is not sufficient to trigger and maintain a full autophagic response, thus suggesting that the activation of autophagy by 20E is mediated by multiple downstream targets.
In order to study the role of autophagy and apoptosis in this setting we used specific inhibitors. The impairment of the autophagic flux, through administration of chloroquine, determines an increased degeneration of the larval midgut epithelium and higher levels of caspase activity compared to controls, while the inhibition of caspase activation, by using z.vad.fmk, leads to a severe delay in the degradation of the epithelium. These data demonstrate that, while autophagy has a pro-survival role in this setting, apoptosis is the major process that drives the demise of the larval midgut during metamorphosis
La rete di assistenza alla cronicità: epidemiologia di un fenomeno sanitario e socio-culturale.
No full textE’ noto che i pazienti affetti da una patologia cronica - o da una combinazione di malattie croniche (pluripatologie) - hanno un rischio di morbilità e di mortalità più alto rispetto al resto della popolazione indenne. Non è però scontato che la malattia degeneri - come fa intendere la denominazione di uso corrente di malattia cronico-degenerativa, peggiorando la qualità della vita della persona in termini di deterioramento delle proprie funzioni e riduzione della propria autonomia. Per evitare ciò è indispensabile mettere in atto una sequenza di azioni perfettamente concatenate sia di salute pubblica, a impronta preventiva, sia di tipo clinico assistenziale nei confronti del singolo paziente. Infatti, la consapevolezza dell’individuo gioca un ruolo determinante, configurandosi come fattiva partecipazione inizialmente al percorso di salute e poi, eventualmente - nel caso di diagnosi di malattia - al piano di cura. La gran parte del lavoro degli operatori della sanità in tema di malattie croniche consiste nella divulgazione approfondita della conoscenza dei fattori di protezione e dei fattori di rischio rispetto alle malattie medesime. Segue una sensibilizzazione alle possibilità offerte dalle tecniche di diagnosi precoci (screening), all’interno di uno schema epidemiologicamente definito di correlazione tra malattie, fasce di età e sesso. Infine, nel terreno delle singole specialità, si delineano i percorsi di cura specifici per la patologia e adatti al singolo malato. Appare evidente che i portatori di interessi, all’interno del panorama appena tracciato per sommi capi, sono diversi, in un intersecarsi di distinte competenze e di professionalità. L’obiettivo dello studio è quello di confrontare le soluzioni finora proposte a livello regionale, alla luce di nuove frontiere e di limiti di sostenibilità economica del sistema sanitario
The invasive tree squirrel Callosciurus erythraeus in Italy: ecology, management and impact on the native squirrel Sciurus vulgaris.
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Numerical iterative methods for nonlinear problems.
No full textThe primary focus of research in this thesis is to address the construction of iterative methods for nonlinear problems coming from different disciplines. The present manuscript sheds light on the development of iterative schemes for scalar nonlinear equations, for computing the generalized inverse of a matrix, for general classes of systems of nonlinear equations and specific systems of nonlinear equations associated with ordinary and partial differential equations. Our treatment of the considered iterative schemes consists of two parts: in the first called the ’construction part’ we define the solution method; in the second part we establish the proof of local convergence and we derive convergence-order, by using symbolic algebra tools. The quantitative measure in terms of floating-point operations and the quality of the computed solution, when real nonlinear problems are considered, provide the efficiency comparison among the proposed and the existing iterative schemes. In the case of systems of nonlinear equations, the multi-step extensions are formed in such a way that very economical iterative methods are provided, from a computational viewpoint. Especially in the multi-step versions of an iterative method for systems of nonlinear equations, the Jacobians inverses are avoided which make the iterative process computationally very fast. When considering special systems of nonlinear equations associated with ordinary and partial differential equations, we can use higher-order Frechet derivatives thanks to the special type of nonlinearity: from a computational viewpoint such an approach has to be avoided in the case of general systems of nonlinear equations due to the high computational cost.
Aside from nonlinear equations, an efficient matrix iteration method is developed and implemented for the calculation of weighted Moore-Penrose inverse. Finally, a variety of nonlinear problems have been numerically tested in order to show the correctness and the computational efficiency of our developed iterative algorithms
Sguardi tra Cielo e Terra: per una fenomenologia simbolica della Visione. Looks between Heaven and Earth: for a phenomenology of Vision
No full textCosa vediamo nelle immagini che guardiamo? Qual è il rapporto che il nostro sguardo intrattiene con il Mondo e con il Kosmos? In che modo possiamo renderci visibili a noi stessi attraverso l’esercizio di un’autentica Visione? Come porre le immagini percepite in relazione con la profondità inconscia? E come farle dialogare con l’Anima dell’uomo? Questi sono i principali interrogativi che si è posta la presente ricerca.
In particolare, sono state avvicinate le immagini archetipiche che emergono dalla relazione oculoceleste, in un’ottica prevalentemente psicoanalitica junghiana. Nell’analisi, tuttavia, si è fatto anche riferimento alle strutture antropologiche dell’immaginario di Gilbert Durand, alle rêveries cosmiche e poetiche di Gaston Bachelard, al mundus imaginalis di Henry Corbin, alla fenomenologia della percezione di Maurice Merleau-Ponty, al pensiero di James Hillman e al De vita coelitus comparanda di Marsilio Ficino, oltre che alla tradizione ermetica e all’Arte alchemica.
Al fine di evidenziare lo stretto rapporto tra fenomenologia della percezione e fenomenologia dell’immaginazione, si è fatto appello, inoltre, alla mitologia, alla prosa, alla poesia, all’Arte, citando anche testi cinematografici e brani musicali. Alla musica, in particolare, sono stati intitolati i capitoli della ricerca al fine di mettere in risalto lo stretto rapporto intercorrente tra l’andamento dei movimenti astrali e le strutture anatomico-funzionali dell’occhio. Proprio dalla musica, dalla danza delle sfere e dal movimento reiterato delle palpebre sono emerse le componenti erotiche, sintetico-copulative e femminili della Visione. Aspetti che meritano di essere riconsiderati e rivalutati, se si vuole promuovere una rinascenza dello sguardo. Condizione quest’ultima necessaria per approdare a una Visione capace di dialogare con le istanze profonde della psiche, sottraendosi così all’ossessione contemporanea della visibilità che ci rende, sostanzialmente, invisibili a noi stessi.
What can we see in the pictures we look at? What is the relationship our look has with the World and the Kosmos? How can we make ourselves visible to ourselves through the exercise of an authentic Vision? How can we put the perceived images in relationship with the deep unconscious? And how can we make them talk to the man’s Soul? This study raises these main questions.
In particular, archetypal images that emerge from the eye-heaven relationship were compared from a predominantly psychoanalytic Jungian point of view. Nevertheless, the analysis also made reference to the anthropological structures of the imagery of Gilbert Durand, the cosmic and poetic rêveries of Gaston Bachelard, the mundus imaginalis of Henry Corbin, the phenomenology of perception of Maurice Merleau-Ponty, the thought of James Hillman and the De vita coelitus comparanda of Marsilio Ficino, as well as the hermetic tradition and alchemic Art. In order to highlight the close relationship between phenomenology of perception and phenomenology of imagination, also mythology, prose, poetry and Art were taken into consideration, citing cinematographic texts and music pieces, too. Music, in particular, was named in the chapters of the study in order to highlight the close relationship between the evolution of astral movements and the anatomical and functional structures of the eye. The erotic, syntheticcopulative and female components of Vision emerged from the music, the dance of the spheres and the repeated movement of the eyelids. All these aspects are worth being reconsidered and reevaluated, if we want to promote a Renaissance of the look. This is a condition necessary to achieve a Vision that can interact with the deep aspirations of the psyche, thus escaping from the contemporary obsession of visibility that makes us invisible to ourselves
Identificazione di una putativa proteina nel veleno di Toxoneuron nigriceps
No full textGli insetti parassitoidi compiono il loro sviluppo larvale a spese di insetti ospiti.
Durante l’ovideposizione nell’ospite, la femmina del parassitoide inietta un veleno, al fine di regolarne la fisiologia e favorire lo sviluppo della propria prole.
Il presente progetto di dottorato ha avuto come scopo l’identificazione delle proteine del veleno dell’imenottero Toxoneuron nigriceps (Viereck) (Hymenoptera, Braconidae), parassitoide endofago di stadi larvali di Heliothis virescens (Fabricius) (Lepidoptera, Noctuidae). La composizione biochimica e le attività tossiche di questo veleno risultano tutt’oggi completamente sconosciute.
L’intero trascrittoma della ghiandola del veleno di Toxoneuron nigriceps è stato sequenziato e analizzato mediante strumenti bioinformatici. Tale analisi ha evidenziato un’ ampia varietà in termini di composizione proteica del veleno.
Il lavoro sperimentale è stato suddiviso in due fasi: nella prima, denominata “bioinformatica”, si è analizzato, mediante tools bionformatici, il trascrittoma de novo delle ghiandole del veleno, realizzato ed assemblato con l’impiego della tecnologia ‘RNA-Sequencing’ (RNA-Seq). Nella seconda fase, denominata “analitica”, il veleno è stato dapprima quantificato e successivamente sottoposto ad uno stadio di separazione mediante elettroforesi monodimensionale (SDS-PAGE) e bidimensionale (2D-PAGE). Gli spot sono stati escissi e sottoposti, nella fase identificativa, ad analisi di spettrometria di massa ESI MS-MS previa digestione con tripsina. Le analisi effettuate hanno permesso di identificare inequivocabilmente una proteina denominata “Heparanase”. Si tratta di un’endoglicosidasi che taglia l’eparan solfato (HS) e partecipa quindi alla degradazione e al rimodellamento della matrice extracellulare. Molte eparanasi sono coinvolte nel miglioramento dell’Akt signaling, nella migrazione cellulare mediata dal fosfatidilinositolo-3-chinasi (PI3K) e dalla chinasi p38, e nella sovraregolazione del fattore di crescita dell’endotelio vascolare (VEGF), proteine presenti nei veleni degli Imenotteri studiati
Lack of Mecp2 interferes with cortical progenitors proliferation and differentiation.
No full textRett syndrome (RTT) is a progressive neurological disorder affecting 1 in 10.000 live female births; nowadays is the most common genetic cause of intellectual disability in females. RTT is characterized by a normal pregnancy period and an apparently normal early post-natal phase. Around 6-18 months of life children lose all the previously acquired skills and manifest overt symptoms (as autistic features, loss of purposeful hand use, respiratory abnormalities and motor dysfunctions). Classical RTT cases are linked to mutations in the X-linked MECP2 gene that encodes for the Methyl-CpG-Binding Protein 2 (MeCP2), a multi-functional protein ubiquitously expressed in the body.
The apparently normal early post-natal period explains why most of the studies in the RTT field focused post-natally, while the role of the protein during early development was only partially investigated. However, nowadays, many evidences demonstrating the presence of earlier symptoms in both girls and RTT animal models are arising. Therefore, we decided to investigate the role of Mecp2 during early/embryonic cortical development, as the cerebral cortex morphology is altered in RTT and patients manifest cognitive impairments. We demonstrated that E15.5 cortices are characterized by an altered expression profile suggestive of a delay in neuronal maturation. Thus, we analysed neuroprogenitors highlighting that Mecp2 absence slightly alters the cell cycle progression, lengthening the permanence of cells in the G1 phase. This possibly impairs the proper definition of cell fate, as Mecp2 null embryonic cortices are characterized by the increment of cells transitioning from progenitors to post-mitotic neurons. Interestingly, the altered switch is in line with the maturation delay suggested by our transcriptional analysis, as the impaired fate definition can delay the expression of genes characterizing more mature cells as different glutamate receptors and ion channels subunits. Cells, delayed in their maturation since early/embryonic phases, are not properly responding to external stimuli, resulting in their defective integration in the forming network, which is a feature common to many autistic spectrum disorders. Our data represent a first evidence of the importance of Mecp2 during embryonic development and suggest that the phenotype characterizing RTT patients is due to the sum of different alterations occurring since embryonic development and worsening through life
Delay differential equations in a nonlinear cochlear model.
No full textThe human auditory system performs its primary function in the cochlea, the main organ of the inner ear, where the spectral analysis of a sound signal and its transduction into a neural signal occur. It is filled with liquid and divided in two cavities by the basilar membrane (BM). A sound stimulus propagates in air as an acoustic pressure wave through the outer and the middle ear. The pressure of the stapes on the oval window (boundary between the middle and the inner ear) causes the cochlear fluid to flow between the two cavities through a hole at the end of the BM. A spatial partial differential equation of fluid-dynamics describes this physical process. As a consequence of the differential pressure between the two cavities, each micro-element of the BM oscillates as a forced damped harmonic oscillator. The BM displacement is amplified by the overlying outer hair cells (OHCs) through a nonlinear nonlocal active feedback mechanism. The latter can be modeled by means of various representations. Among them, the delayed stiffness model of Talmadge et al. (J. Acoust. Soc. Am. 104, 1998) has been considered in this thesis. Specifically, the cochlear nonlinearity is introduced as a quadratic function of the BM displacement in the passive linear damping function. Moreover, the active mechanism is described by two additional forces, each one proportional to the BM displacement delayed by a slow and a fast feedback constant time, respectively. According to this model, a time delay differential equation (DDE) of the second order describes the oscillating dynamics of the BM. A different formulation of the nonlinear active mechanism, driven by the OHCs, is expressed as a nonlinear function of the BM velocity by the anti-damping model of Moleti et al. (J. Acoust. Soc. Am. 133, 2013). In this case the model equations do not contain time delays.
The numerical integration of the above mentioned models has been obtained by finite differencing with respect to the space variable in the state space, as introduced by Elliott et al. (J. Acoust. Soc. Am. 122, 2007), and then integrating in time with the adaptive package introduced by Bertaccini and Sisto as a modification of the popular Matlab ode15s package (J. Comput. Phys. 230, 2011). The semidiscrete formulation of the delayed stiffness model and the anti-damping model has a non trivial mass matrix, and eigenvalues of the system matrix with large negative real part and imaginary part. That is why an implicit solver with an infinite region of absolute stability should be used. Therefore, the customized Matlab ode15s package by Bertaccini and Sisto seems to be the convenient choice to integrate the problem at hand numerically. In particular, for the delayed stiffness model, an integrator for constant DDEs (the method of steps; Bellen and Zennaro, Oxford University Press 2003) has been formulated and based on the customized ode15s.
All these topics have been discussed in this doctoral thesis, which is subdivided in the following chapters.
Chapter 1 describes the anatomy of the human ear, with special regard to the cochlea. Some experimental evidences about the cochlear mechanisms are discussed, in order to support the cochlear modeling. Two physical models with one degree of freedom are shown: the anti-damping model of Sisto et al. (J. Acoust. Soc. Am. 128, 2010) and Moleti et al. (J. Acoust. Soc. Am. 133, 2013), and the delayed stiffness model of Talmadge et al. (J. Acoust. Soc. Am. 104, 1998).
Chapter 2 discusses the general theory of DDEs, with greater reference to constant and time dependent DDEs from Bellen and Zennaro (Oxford University Press 2003). Existence and uniqueness of time dependent DDEs are briefly analyzed, while the method of steps is shown as a basic approach to find a numerical approximation of the DDEs solution. According to this method, IVPs of constant DDEs (as for the semidiscrete delayed stiffness model) are turned into IVPs of ODEs in a subinterval (of length less than or equal to the time delay) of the whole integration interval. Each IVP of ODEs can be integrated by means of any ODEs numerical method, and its convergence is then discussed.
Chapter 3 describes the main tools used to find an approximate solution of the considered models. In particular, the discretization for spatial partial derivatives by means of finite differences is shown. Such a representation turns a model, which is continuous in the space-time domain, into a semidiscrete model to be integrated in time. The models considered in this thesis are stiff, so the phenomenon of stiffness is discussed and the ode15s package of Matlab for integrating stiff ODEs is described. Nevertheless, greater benefits can be obtained by using the ode15s package customized by Bertaccini and Sisto as a hybrid direct-iterative solver which exploits Krylov subspace methods.
Chapter 4 shows the semidiscrete formulation of the continuous models (anti-damping model and delayed stiffness model) in the state space with respect to the spatial variable, as introduced by Elliott et al. (J. Acoust. Soc. Am. 122, 2007). The algebraic properties of the semidiscrete models are discussed in order to show why the customized ode15s package may perform a faster numerical integration of the semidiscrete models and how this solver can be used in an integration numerical technique for constant DDEs (the method of steps).
Chapter 5 shows the results produced by the numerical experiments of the delayed stiffness model by supplying a sinusoidal tone, and compares them with the numerical results produced by the anti-damping model. Some considerations about the numerical approach of the time integration are also discussed, and a part of the simplified code used for integrating the semidiscrete delayed stiffness model, is reported. The results are comparable with those obtained by the anti-damping model, and then the numerical experimental evidences seem to justify the proposed integration technique for constant DDEs. Delayed model properties of tonotopicity, anti-damping and nonlinearity are verified, as well as the dependence of the approximate solution on some free parameters of the model. The cochlear response described by the delayed stiffness model shows a typical tall and broad BM activity pattern. This behavior is also found in the numerical results of a model with two degree of freedom produced by Neely and Kim (J. Acoust. Soc. Am. 79, 1986) and Elliott et al. (J. Acoust. Soc. Am. 122, 2007)
Ni droite ni gauche: la risposta anticonformista alla crisi degli anni Trenta in Francia.
No full textNonconformists thirties who identified with the slogan "ni droite, ni gauche" had many things in common including the enormous sense of weariness towards a parliamentary democracy in which the parties were unable to cope with the economic crisis, political, social, cultural and value them was overwhelming; then all supported the idea that we should reduce the excessive influence of the state and its bureaucracy and cumbersome resulting in events that could easily be addressed by other institutions closer to citizens, first of all the common. The answers that such groups took to the crisis were mainly conceptual, this was their big problem, could not in fact indicate a clear line of political action. But reflecting on how they developed, one can not grasp important lessons that can be reused to understand and deal with a "today" which, although changed over that period, is often faced with very similar problems as the economic crisis, the resulting in unemployment, the depersonalization and the inability of political parties and governments to provide concrete answers to the needs of citizens. Here, in this my journey into the heart of the French dissidents, those who tried different responses to the crisis than those of the "terrible simplifiers": fascism, Nazism and communism advocated killing the individual and his subservience to the state, it remains - above all else - a reflection on the person. It should then meditate on these issues in an age like ours, because in the serious situation we are living the only hope to build a dynamic and positive political perspective is to create a society which, as rightly assumed Alexandre Marc, will be to force of things «à taille humaine»