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Acuzie psichiatriche nel migrante: un’indagine sul territorio di Gallarate (VA) in una cornice teorica transculturale.
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Aeromonas spp: model for monitoring the impact and diffusion of antibiotic compounds in water environments.
Get PDFAntibiotic resistant bacteria and antibiotic resistance genes cause increasing problems in clinical setting and are worldwide considered emerging environmental contaminants, but little is known about their fate in the receiving environment and how natural microbial populations may be affected. In the environment, antibiotic resistant bacteria (e.g. pathogen) may die but their resistance determinants may become part of the environmental gene pool via horizontal gene transfer to environmental bacteria. From this localization, resistance genes may move back to human and animal bacteria via food and drinking water. Natural environment, especially water, is considered a “hot spot” for spread of antibiotics resistance in this scenario Aeromonas spp. were considered the model of hydric microorganisms exposed to the actions of residual antibiotic compounds and to the aquatic resistome, whereas Faecal Coliforms represented the allochthonous population contaminating the aquatic environment. In order to investigate how these two bacterial populations could be influenced by potential antibiotic pollution, we want to examine the presence, the distribution and the transferability of transposons, integrons, and plasmids in Aeromonas spp. and Faecal Coliforms isolated from different aquatic environments submitted to a diverse degree of antibiotic contamination. In this work, we want to highlight if there are common genetic determinants in the two populations and check the potential transferability of these genetic determinants. Conjugation, natural transformation and transduction are the three mechanisms of horizontal antibiotic resistance genes transfer among bacteria. Additionally, we want to investigate if Aeromonas could also be a good donor in mating experiments with other bacteria and if it is able to naturally acquired free DNA from the environment and if Aeromonas DNA could be incorporated by natural competent bacteria. Finally we want to study lytic and lysogenic bacteriophages of Aeromonas spp., investigate the presence of resistance genes on phage DNA and evaluate if phage can transfer these resistance genes by transduction experiments
Numerical iterative methods for nonlinear problems.
Get PDFThe 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
Identificazione di una putativa proteina nel veleno di Toxoneuron nigriceps
Get PDFGli 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
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)
Gelectin-1 is a new potential therapeutic target in multiple myeloma
No full textGalectin-1 (Gal-1) is a lectin, involved in several processes related to cancer, including immunosuppression, angiogenesis, hypoxia, and metastases. Currently, the role of Gal-1 in multiple myeloma (MM) pathophysiology and in MM-induced angiogenesis is unknown. Firstly, we found that Gal-1 was expressed by malignant plasma cells in the bone marrow microenvironment. Moreover, our data demonstrated that Gal-1 expression was up-regulated in MM cells by hypoxia treatment (1% of O2).Furthermore, the stable knock-down of Hypoxia Inducible Factor-1α, the master regulator of oxygen homeostasis, in human myeloma cell lines (HMCLs) markedly down-regulated Gal-1 expression. Thereafter, we found that the stable inhibition of Gal-1 by lentiviral vector short hairpin RNA (shRNA) anti-Gal-1 did not affect the proliferation and survival of MM cells, but significantly modified their transcriptional profiles, both in normoxic and hypoxic conditions. Notably, Gal-1 inhibition in MM cells significantly down-regulated genes involved in promoting tumor angiogenesis such as CCL2 and MMP9, and up-regulated some putative anti-angiogenic genes, including SEMA3A and CXCL10. In line with these observations, we found that Gal-1 suppression significantly decreased the pro-angiogenic proprieties of HMCLs, assessed by in vitro angiogenesis assay. Finally, we found that NOD-SCID mice, injected subcutaneously with HMCLs carrying a stable infection with lentiviral vector shRNA anti-Gal-1, showed a reduction in tumor volume and a significant reduction in the plasmacytomas microvascular density, compared to mice inoculated with HMCLs carrying a stable infection with the control vector. In a different set of experiments, a HMCL JJN3 infected with shRNA anti-Gal-1 and with control vector were injected in NIH-III SCID mice, an intratibial mouse model. We found that the anti-Gal-1 group developed tumors reduced in length, thickness, width and volume size and, in addition, developed fewer and smaller lytic lesions on x-ray compared to the control group.
Overall, our data indicate that Gal-1 exerts a role in MM pathophysiology and in MM-induced angiogenesis and its inhibition in MM cells significantly reduced tumor growth in vivo, suggesting that Gal-1 is a new potential therapeutic target in MM
A novel role of CDKL5 in the regulation of mitotic spindle assembly and microtubule organization.
Get PDFMutations in the CDKL5# gene, located on Xp22, are the main cause of CDKL56 disorder characterized by the onset of epilepsy before 3 months of age, severe developmental delay and RTT6like features. Besides its functions in post6mitotic neurons, a recent work shows that the loss of CDKL5 influences the proliferation rate of neuronal precursors suggesting its role also in proliferating cells. However, the molecular mechanism through which CDKL5 acts on this cellular process is still unknown.
In this study we demonstrate the presence of CDKL5 at the mitotic centrosome and midbody. Importantly, the ablation of CDKL5 induces prolonged prometaphases, aberrant/multipolar spindle assembly and misaligned chromosomes. Furthermore, we show that, similar to many centrosomal proteins, CDKL5 influences microtubule organization. At the molecular level, we find that CDKL5 interacts with the scaffold protein IQGAP1, a regulator of Rac1, which regulates many cytoskeleton functions thanks to its ability to interact both with actin and plus end microtubule binding proteins (+TIPs). CDKL5 is required for the correct localization of IQGAP1 at the leading edge of polarized cells and down6regulation of CDKL5 reduces the capacity of IQGAP1 to interact with its effector proteins Rac1 and CLIP170, a +TIP that promotes microtubule stabilization at the cell cortex. Altogether, our data suggest that CDKL5 influences cell cycle progression through its centrosomal accumulation and cellular morphology through its interaction with microtubule associated proteins. We believe that these data will pave the way for a further understanding of the impact of CDKL5 in neuronal and non6neuronal cell
Distribuzione e valutazione del rischio di composti perfluorati in bacini fluviali italiani.
No full textPerfluoroalkyl substances (PFASs) are emerging pollutants with so peculiar physico-chemical characteristics that these compounds found wide applications in several industrial processes and daily products. Their characteristics and the wide use make them widespread in all environmental compartments, very persistent and partially bioaccumulable.
A past survey at the basin closures of the main European rivers highlighted that river Po was the most contaminated (200 ng/L) by perfluorooctanoic acid (PFOA), the currently most diffused perfluoroalkyl acid (PFAA). This evidence led to a funded project which aimed to evaluate the PFAA distribution in main Italian river basins and to assess the correlated environmental and sanitary risks.
An UHPLC-MS/MS multi-residue method based on an on-line SPE procedure was developed for the simultaneous determination of 12 PFAAs to support the sampling program in river basins that covered about 40% of the Italian surface area and about 45% of the Italian population.
In Italy the most important sources of PFAA are fluorochemical plants, followed by discharges from tannery and textile industrial districts, while the contribution of urban areas is limited. Considering the most populated and industrialized Italian area, the river Lambro basin, Lombardy, detailed mass balance of the emission sources have been carried out.
The environmental risks for the aquatic ecosystem were evaluated in river Bormida (Piedmont) downstream the discharge of a fluoropolymer plant which is the most significant source of PFOA in Italy. An effect-based approach was applied to the study of macrobenthic community, evaluating the ecological quality, the community structure and the genetic variance
