Quantitative constraint-based computational model of tumor-to-stroma coupling via lactate shuttle

Cancer cells utilize large amounts of ATP to sustain growth, relying primarily on non-oxidative, fermentative pathways for its production. In many types of cancers this leads, even in the presence of oxygen, to the secretion of carbon equivalents (usually in the form of lactate) in the cell’s surroundings, a feature known as the Warburg effect. While the molecular basis of this phenomenon are still to be elucidated, it is clear that the spilling of energy resources contributes to creating a peculiar microenvironment for tumors, possibly characterized by a degree of toxicity. This suggests that mechanisms for recycling the fermentation products (e.g. a lactate shuttle) may be active, effectively inducing a mutually beneficial metabolic coupling between aberrant and non-aberrant cells. Here we analyze this scenario through a large-scale in silico metabolic model of interacting human cells. By going beyond the cell-autonomous description, we show that elementary physico- chemical constraints indeed favor the establishment of such a coupling under very broad conditions. The characterization we obtained by tuning the aberrant cell’s demand for ATP, amino-acids and fatty acids and/or the imbalance in nutrient partitioning provides quantitative support to the idea that synergistic multi-cell effects play a central role in cancer sustainmen

Experimenting with mashup features in the mobile space

Social network websites like Facebook and MySpace are widely used worldwide and the mashup content aggregation technology is gaining attention by many software developers and CTOs which are looking at it as a potential replacement of portal technologies. At the same time, social network websites are attracting the interest of some firms and CRM software vendors. With flat-rate pricing offers for mobile data traffic by the most important mobile telephony operators a growth in demand of mobile data services is expected. The aim of this thesis is to develop a mobile mashup of context aware news provisioning and social networking services to be integrated into an existing mobile mall software. First we introduce social network analysis, the theory lying behind social networks, and its most relevant findings. We define what is a social network website and how it differs from a mobile social network. To understand what influences the adoption of mobile data services a model based on the Triandis theory of explaining human behaviour is introduced and used. We will then analyse the state of the art in social network websites, event planning services and technologies to deliver news from different sources. The analysis will enable us to identify what are the most important services to include directly in the mashup and which ones have to be developed internally. Lastly we introduce the technologies used to develop the mobile mashup application and display the most relevant design and development work done during the thesis

Noise processing by microRNA-mediated circuits: The Incoherent Feed-Forward Loop, revisited

The intrinsic stochasticity of gene expression is usually mitigated in higher eukaryotes by post-transcriptional regulation channels that stabilise the output layer, most notably protein levels. The discovery of small non-coding RNAs (miRNAs) in specific motifs of the genetic regulatory network has led to identifying noise buffering as the possible key function they exert in regulation. Recent in vitro and in silico studies have corroborated this hypothesis. It is however also known that miRNA-mediated noise reduction is hampered by transcriptional bursting in simple topologies. Here, using stochastic simulations validated by analytical calculations based on van Kampen's expansion, we revisit the noise-buffering capacity of the miRNA-mediated Incoherent Feed Forward Loop (IFFL), a small module that is widespread in the gene regulatory networks of higher eukaryotes, in order to account for the effects of intermittency in the transcriptional activity of the modulator gene. We show that bursting considerably alters the circuit's ability to control static protein noise. By comparing with other regulatory architectures, we find that direct transcriptional regulation significantly outperforms the IFFL in a broad range of kinetic parameters. This suggests that, under pulsatile inputs, static noise reduction may be less important than dynamical aspects of noise and information processing in characterising the performance of regulatory elements

The spread of Caulerpa cylindracea in Calabria (Italy) and the effects of shipping activities

A survey to state the spread of Caulerpa cylindracea in the Calabrian Tyrrhenian coasts has been undertaken. The research aims to value the role of shipping activities in the ten-year’s study from 1999 to 2009, as a vector in the spreading of the species. The outcome of this study has shown that, during the last ten years, the species has colonized most of the regional coastline, on all kinds of substrata, in areas closed to harbours and subjected to high rate of sedimentation. The main effects of Caulerpa cylindracea colonization have resulted in a gradual decrease of crustose species while the turf ones have increased their abundance, altering the native structure of the macroalgal assemblages. These results confirm the extremely invasive behaviour of this strain in the Calabrian Tyrrhenian coasts and, more generally, in the Mediterranean Sea

The alien alga Caulerpa taxifolia (Vahl) C. Agardh var. distichophylla (Sonder) Verlaque, Huisman and Procaccini move their northern and western limits.

Caulerpa taxifolia (Vahl) C. Agardh var. distichophylla (Sonder) Verlaque, Huisman and Procacini is a green invasive alga recently reported in the Mediterranean Sea for the first time in 2007. The first record was in Turkey in 2007 and later it has been reported in Sicily (Italy, in 2009), Cyprus (in 2013), Malta (in 2015), Rhodes (in 2016) and Lybia (2017). In the current study we present additional records of this species which expanding its range into the Eastern and Western Mediterranean Sea (Eastern and Western Sicilian shoreline, Calabrian Tyrrhenian coast, Sardinia and Tunisia) as well as in the eastern Mediterranean basin. Our specimens were collected on various substrates and were identified trough morphological methods

Levels of heavy metals in wetland and marine vascular plants and their biomonitoring potential : a comparative assessment

The present study investigated the levels of As, Cd, Cr, Cu, Hg, Mn, Ni, Pb and Zn in the seagrasses Posidonia oceanica and Cymodocea nodosa, and in the wetland macrophytes Phragmites australis, Arundo donax, Typha domingensis, Apium nodiflorum, and Nasturtium officinale. Results showed that the bioaccumulation capacity from sediments, translocation, total levels in plant tissues, and bioindication of metals in sediments, are generally species-specific. In particular, the patterns of metals in the aquatic plants studied were overall independent of ecology (coasts vs wetlands), biomass, anatomy (rhizomatous vs non rhizomatous plants), and life form (hemicrytophytes vs hydrophytes). However, marine phanerogams and wetland macrophytes shared some characteristics such as high levels of heavy metals in their below-ground organs, similar capacity of element translocation in the rhizosphere, compartmentalization of metals in the different plant organs, and potential as bioindicators of Cu, Mn and Zn levels in the substratum. In particular, the present findings indicate that, despite ecological and morphological similarities, different plant species tend to respond differently to exposure to heavy metals. Furthermore, this seems to result from the species individual ability to accumulate and detoxify the various metals rather than being attributed to differences in their ecological and morpho-anatomical characteristics.peer-reviewe

Biochemical data from the characterization of a new pathogenic mutation of human pyridoxine-5'-phosphate oxidase (PNPO)

PNPO deficiency is responsible of severe neonatal encephalopathy, responsive to pyridoxal-5’-phosphate (PLP) or pyridoxine. Recent studies widened the phenotype of this condition and detected new genetic variants on PNPO gene, whose pathogenetic role and clinical expression remain to be established. One of these mutations, Arg116Gln, is of particular interest because of its later onset of symptoms (beyond the first months of life) and its peculiar epileptic manifestations in patients. This protein variant was expressed as recombinant protein in E coli, purified to homogeneity, and characterized with respect to structural and kinetic properties, stability, binding constants of cofactor flavin mononucleotide (FMN) and product (PLP) in order to define the molecular and structural bases of its pathogenicity. For interpretation and discussion of reported data, together with the description of clinical studies, refer to the article [7][1] (doi: 10.1016/j.ymgme.2017.08.003)

The role of puberty and adolescence in the pathobiology of pediatric multiple sclerosis

Abstract Multiple sclerosis (MS) is increasingly recognized in the paediatric age. In a smaller, but well-established, proportion of paediatric MS patients [20% of total paediatric MS cases: 0.2% to 0.7% of the total MS patients] the onset of disease is before 10 years of age [pre-pubescent (childhood) MS]; in the majority [80%] of paediatric MS patients, however [1.7% to 5.6% of the total MS population], the onset of disease is between 10 and 18 years [post-pubertal (juvenile) MS]. Notably, while pre-pubertal MS occurs almost equally in both genders (female/male ratio = 0.9:1; reverting to 0.4–0.6/1 in pre-school MS children) the female/male ratio rises to 2.2/3:1 in the post-pubertal age. Interestingly, precocious puberty has been associated to: (a) a higher risk of developing MS; and (b) a more severe disease course. In addition to that, males are more susceptible to MS (and manifest more neurodegeneration) than females the latter being however more inflammatory than males; pregnancy however reduces MS relapses. All the above findings led to the suggestion of an underlying female sex hormonal involvement in the pathophysiology of MS vs. a protective role of male sex hormones. Epigenetic perspectives indicate that the interplay between genetic background, environmental triggers and neuroendocrine changes, typically occurring around the time of adolescence, could all play a combined role in initiating and/or promoting MS with onset in the paediatric age including many of the most frequent disease-associated risk factors (e.g., overweight/obesity, low vitamin D levels, reduced sunlight exposure, Epstein-Barr virus infection). According to this proposed complex multifactorial model, susceptibility to MS may be thus acquired during pre-pubertal age and children have probably to wait until the adolescence to manifest their first clinical signs/symptoms

Bioalcohol Reforming: An Overview of the Recent Advances for the Enhancement of Catalyst Stability

The growing demand for energy production highlights the shortage of traditional resources and the related environmental issues. The adoption of bioalcohols (i.e., alcohols produced from biomass or biological routes) is progressively becoming an interesting approach that is used to restrict the consumption of fossil fuels. Bioethanol, biomethanol, bioglycerol, and other bioalcohols (propanol and butanol) represent attractive feedstocks for catalytic reforming and production of hydrogen, which is considered the fuel of the future. Different processes are already available, including steam reforming, oxidative reforming, dry reforming, and aqueous-phase reforming. Achieving the desired hydrogen selectivity is one of the main challenges, due to the occurrence of side reactions that cause coke formation and catalyst deactivation. The aims of this review are related to the critical identification of the formation of carbon roots and the deactivation of catalysts in bioalcohol reforming reactions. Furthermore, attention is focused on the strategies used to improve the durability and stability of the catalysts, with particular attention paid to the innovative formulations developed over the last 5 years

Kinetic Modeling of Solketal Synthesis from Glycerol and Acetone Catalyzed by an Iron(III) Complex

In the last few years, the depletion of the fossil sources and their negative effect on the environment has led to find new alternatives; among these, biodiesel is considered one of the most promising for this purpose. Biodiesel can be produced from the transesterification of vegetable oils or animal fats, obtaining glycerol as a by-product. Glycerol can be used in different processes and one of the most interesting is the condensation with acetone to produce solketal. Among its applications, plasticizers, solvents, and pharmaceutical formulations are the most common. In this work, the attention was focused on the reaction between glycerol and acetone to give solketal promoted by an iron(III) complex. The reaction mechanism was hypothesized, and the kinetics was studied in a batch reactor. Finally, the thermodynamic and kinetic parameters were determined with a reliable model investigating the phenomena that occurred in the reaction network. Keywords