ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences

BACKGROUND: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need to develop novel strategies. RESULTS: We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. CONCLUSION: Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at

Congenital Chagas disease in a Bolivian newborn in Bergamo (Italy)

Chagas disease (CD) is an uncommon disease in Europe. Its epidemiology has changed because of mass migration from Latin America to Europe. Herein we describe a congenital case of CD in a Bolivian newborn in Bergamo, the main city of residence for the Bolivian community in Italy. At delivery, serological analyses evidenced IgG antibodies against Trypanosoma cruzi both in the child and mother, as expected. Hemoscopic analyses on peripheral blood were repeatedly negative during the first months of life. Eventually, thanks to T. cruzi Real Time polymerase chain reaction (RT-PCR) positivity on peripheral blood and development of progressive anemia in the following weeks, congenital Chagas disease was diagnosed and benznidazole-based therapy started. A progressive antibodies' index decrease was observed till negativity (306 days apart). RT-PCR was negative at the end of treatment. Our case is instructive and management of congenital CD is discussed from the perspective of a non-endemic country

RISCHIO, VULNERABILITA' E RESILIENZA TERRITORIALE: IL CASO DELLE PROVINCE ITALIANE

L’obiettivo della tesi è ideare uno schema teorico del concetto multidimensionale di rischio territoriale, applicandolo successivamente ad un caso di studio sulle province italiane. Nel primo capitolo si delinea uno schema teorico del concetto di rischio territoriale, utilizzando una lettura del fenomeno di stampo sistemico, secondo cui il rischio è correlato positivamente a fattori di vulnerabilità territoriale e negativamente a fattori di resilienza. Il territorio viene rappresentato nelle tre dimensioni della sostenibilità, quella economica, sociale e ambientale, seguendo un approccio olistico. Nel secondo si applica lo schema teorico ad uno studio sulle province italiane. Si adotta una metodologia di sintesi a passaggi successivi, che prevede l’applicazione di tecniche multivariate. Si giunge ad un sistema di indicatori ed indici sintetici di vulnerabilità e resilienza economica, sociale e ambientale. Nel terzo si giunge agli indici sintetici di vulnerabilità e resilienza territoriale, confrontando metodi di aggregazione differenti. Si individuano così i sistemi locali più a rischio, perchè più vulnerabili e meno dotati di fattori di risposta al cambiamento. Si evidenziano elementi di originalità a livello di disegno teorico, per la trattazione del tema nelle dimensioni distinte Economia, Società e Ambiente, e a livello empirico, per l’utilizzo di metodologie di sintesi ibride.The aim of the work is to provide a theoretical framework regarding the multidimensional concept of vulnerability of local systems, then applying it to a case study on Italian provinces. The first chapter outlines a theoretical framework of this concept, using a reading of the phenomenon according to a systemic mold, whereby the risk is positively correlated with spatial vulnerability factors and negatively with resilience factors. Region is represented in the three dimensions of sustainability, that is the economic, social and environmental ones, following a holistic approach. The second one applies the theoretical framework for a study on the Italian provinces. We have adopted a method of synthesis by successive steps, which provides the application of multivariate techniques. We arrive at an indicators system and composite indices of economic, social and environmental vulnerability and resilience. In the third one we reach the composite indices of vulnerability and resilience of local systems, comparing different methods of aggregation among themselves. Systems are identified as most at risk, because more vulnerable and less gifted with factors of response to change. Elements of originality are highlighted in terms of theoretical project for the treatment of the theme in the distinct dimensions Economy, Society and Environment, as well as, at empirical level, the usage of hybrid synthesis methods

Cytotoxic effects and apoptotic signalling mechanisms of the sesquiterpenoid euplotin C, a secondary metabolite of the marine ciliate Euplotes crassus, in tumour cells

Most antitumour agents with cytotoxic properties induce apoptosis. The lipophilic compound euplotin C, isolated from the ciliate Euplotes crassus, is toxic to a number of different opportunistic or pathogenic microorganisms, although its mechanism of action is currently unknown. We report here that euplotin C is a powerful cytotoxic and pro-apoptotic agent in mouse AtT-20 and rat PC12 tumour-derived cell lines. In addition, we provide evidence that euplotin C treatment results in rapid activation of ryanodine receptors, depletion of Ca2+ stores in the endoplasmic reticulum (ER), the release of cytochrome c from the mitochondria, activation of caspase-12, and activation of caspase-3, leading to apoptosis. Intracellular Ca2+ overload is an early event which induces apoptosis and is parallelled by ER stress and the release of cytochrome c, whereas caspase-12 may be activated by euplotin C at a later stage in the apoptosis pathway. These events, either independently or concomitantly, lead to the activation of the caspase-3 and its downstream effectors, triggering the cell to undergo apoptosis. These results demonstrate that euplotin C may be considered for the design of cytotoxic and pro-apoptotic new drugs.L'articolo è disponibile sul sito dell'editore http://www.springerlink.com

EFFICIENT SIMULATION TOOL TO CHARACTERIZE THE RADAR CROSS SECTION OF A PEDESTRIAN IN NEAR FIELD

none4A simulation tool to characterize the radar cross section of a pedestrian in near field is presented in the paper. The tool has been developed in order to predict and optimize the performance of the short-range radar systems employed in autonomous vehicle operations. It is based on an analytical model which joins the modeling of the human body with the theory of the physical optics. Our studies first focused on the implementation of the electromagnetic code where the human body, the radiation properties of the antenna and the scenario to be analyzed have been analytically expressed. Then, the proposed model has been validated in terms of accuracy comparing simulated and experimental data regarding the radar cross section of a metal sphere and of an adult, in the frequency range 23-28 GHz. In the end, an evaluation of the performance in terms of required computer memory and execution time has been carried out, comparing the proposed simulation tool with other numerical computational methods.openManfredi, Giovanni; Russo, Paola; De Leo, Alfredo; Cerri, GrazianoManfredi, Giovanni; Russo, Paola; De Leo, Alfredo; Cerri, Grazian

Molecular mechanisms of euplotin C-induced apoptosis: involvement of mitochondrial dysfunction, oxidative stress and proteases

The metabolite euplotin C (EC), isolated from the marine ciliate Euplotes crassus, is a powerful cytotoxic and pro-apoptotic agent in tumour cell lines. For instance, EC induces the rapid depletion of ryanodine Ca2+ stores, the release of cytochrome c from the mitochondria, and the activation of caspase-3, leading to apoptosis. The purpose of this study was to gain further insight into the mechanisms of EC-induced apoptosis in rat pheochromocytoma PC12 cells. We found that EC increases Bax/Bcl-2 ratio and that Bax is responsible of the EC-induced dissipation of the mitochondrial membrane potential (Δψm). In addition, EC induces the generation of reactive oxygene species (ROS) without involvement of p53. The inhibition of ROS generation prevents, at least in part, the pro-apoptotic effects of EC as well as the effects of EC on Bax, Δψm and intracellular free Ca2+, indicating a cross-talk between different pathways. However, definition of the effector cascade turns out to be more complex than expected and caspase-independent mechanisms, acting in parallel with caspases, should also be considered. Among them, EC increases the expression/activity of calpains downstream of ROS generation, although calpains seem to exert protective effects.L'articolo è disponibile sul sito dell'editore http://www.springerlink.co

Wireless Sensing for the Respiratory Activity of Human Beings: Measurements and Wide-band Numerical Analysis

An electromagnetic sensing system for the measurement of the respiratory activity is presented. The aims are to demonstrate the feasibility of the proposed approach and in particular to evaluate the effect on the measured signal of the distance between the subject and the sensing apparatus. Moreover, an electromagnetic model of the system, including the monitored subject, is proposed as a tool to solve the problem of selecting working parameters for system design. The sensing system is based on the measurement of the phase variation of the reflection coefficient caused by the respiratory activity. The phase signal compared with the thorax displacement measured by a reference instrument shows a high correlation () for different subject postures (sitting, standing, and lying) and a reduction of the signal amplitude with the distance  dB/cm is reported. The numerical simulations performed on a wide-band highlight the frequencies where the method exhibits the highest sensitivity to thorax movements. The sensitivity can be further improved by reducing the antenna beamwidth. Despite the signal amplitude reduction, the proposed system makes it possible to correctly operate at distances up to 2.5 m

Is “Hit and Run” a Single Word? The Processing of Irreversible Binomials in Neglect Dyslexia

The present study is the first neuropsychological investigation into the problem of the mental representation and processing of irreversible binomials (IBs), i.e., word pairs linked by a conjunction (e.g., “hit and run,” “dead or alive”). In order to test their lexical status, the phenomenon of neglect dyslexia is explored. People with left-sided neglect dyslexia show a clear lexical effect: they can read IBs better (i.e., by dropping the leftmost words less frequently) when their components are presented in their correct order. This may be taken as an indication that they treat these constructions as lexical, not decomposable, elements. This finding therefore constitutes strong evidence that IBs tend to be stored in the mental lexicon as a whole and that this whole form is preferably addressed in the retrieval process