Modelling vicious networks with P-graph causality maps

Clean Technologies and Environmental Policy - P-graph causality maps were recently proposed as a methodology for systematic analysis of intertwined causal chains forming network-like structures....     

Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.     

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.     

Effect of Cultivation Parameters on Fermentation and Hydrogen Production in the Phylum Thermotogae

The phylum Thermotogae is composed of a single class (Thermotogae), 4 orders (Thermotogales, Kosmotogales, Petrotogales, Mesoaciditogales), 5 families (Thermatogaceae, Fervidobacteriaceae, Kosmotogaceae, Petrotogaceae, Mesoaciditogaceae), and 13 genera. They have been isolated from extremely hot environments whose characteristics are reflected in the metabolic and phenotypic properties of the Thermotogae species. The metabolic versatility of Thermotogae members leads to a pool of high value-added products with application potentials in many industry fields. The low risk of contamination associated with their extreme culture conditions has made most species of the phylum attractive candidates in biotechnological processes. Almost all members of the phylum, especially those in the order Thermotogales, can produce bio-hydrogen from a variety of simple and complex sugars with yields close to the theoretical Thauer limit of 4 mol H₂/mol consumed glucose. Acetate, lactate, and L-alanine are the major organic end products. Thermotagae fermentation processes are influenced by various factors, such as hydrogen partial pressure, agitation, gas sparging, culture/headspace ratio, inoculum, pH, temperature, nitrogen sources, sulfur sources, inorganic compounds, metal ions, etc. Optimization of these parameters will help to fully unleash the biotechnological potentials of Thermotogae and promote their applications in industry. This article gives an overview of how these operational parameters could impact Thermotogae fermentation in terms of sugar consumption, hydrogen yields, and organic acids production.     

Double Mutant Cycles as a Tool to Address Folding,Binding, and Allostery

Quantitative measurement of intramolecular and intermolecular interactions in protein structure is an elusive task, not easy to address experimentally. The phenomenon denoted ‘energetic coupling’ describes short- and long-range interactions between two residues in a protein system. A powerful method to identify and quantitatively characterize long-range interactions and allosteric networks in proteins or protein–ligand complexes is called double-mutant cycles analysis. In this review we describe the thermodynamic principles and basic equations that underlie the double mutant cycle methodology, its fields of application and latest employments, and caveats and pitfalls that the experimentalists must consider. In particular, we show how double mutant cycles can be a powerful tool to investigate allosteric mechanisms in protein binding reactions as well as elusive states in protein folding pathways.     

Hydrogen production by silica membrane reactor during dehydrogenation of methylcyclohexane: CFD analysis

A comprehensive computational fluid dynamic model has been developed using COMSOL Multiphysics 5.4 software to predict the behavior of a membrane reactor in dehydrogenation of methylcyclohexane for hydrogen production. A reliable reaction kinetic of dehydrogenation reaction and a permeation mechanism of hydrogen through silica membrane have been used in computational fluid dynamic modeling. For performance comparison, an equivalent traditional fixed bed reactor without hydrogen removal has been also modeled. After model validation, it has been used to evaluate the operating parameters effect on the performance of both the silica membrane reactor and the equivalent traditional reactor as well. The operating temperature ranged between 473 and 553 K, pressure between 1 and 2.5 bar, sweep factor from ?6.22 to 25 and feed flow rate from 1 to 5 × 10^?6 mol/s. The membrane reactor performed better than the equivalent traditional reactor, achieving as best result complete methylcyclohexane conversion and 96% hydrogen recovery.     

Influence of irrigation with lagooned urban wastewater on chemical and microbiological soil parameters in a citrus orchard under Mediterranean condition

The reduced availability of water resources in semi-arid Mediterranean regions requires an efficient use of supply sources. Urban wastewater, after treatment to minimise health hazards, may constitute an important resource for irrigation in areas characterised by intensive agriculture. These considerations have motivated an investigation (during the irrigation season 1996) of the dynamics of microbial biomass in the soil of a citrus orchard in eastern Sicily, which has been irrigated for 15 years with lagooned urban wastewater, to evaluate the effects of this practice on soil fertility. The analyses of parameters regarding soil microbial biomass (microbial carbon and microbial nitrogen, soluble carbon and nitrogen, cumulative respiration, respiratory quotient and enzymatic activity in the soil) have confirmed that the evolution of soil microflora is directly conditioned by the type of water used for irrigation and climatic conditions. Just before the beginning of the irrigation season (May), microbial biomass carbon (MBC), soluble C, cumulative respiration and enzymatic activity were significantly higher in the soil irrigated with wastewater with respect to the same soil irrigated with 'clear' water; the qCO2 was significantly lower. In June, after 1 month of irrigation, both soils showed an increase of all microbial parameters except for enzymatic activity and qCO2 which showed a significant reduction. In September, at the end of the irrigation period, there was a decrease of almost all investigated parameters in both plots, which was more evident in the soil irrigated with 'clear' water. The microbial biomass of the soil irrigated with wastewater, during the irrigation period, did not undergo any negative effects, having an evolution analogous to the plot irrigated with 'clear' water. The use of lagooned wastewater after three lustrums has shown, particularly in the dry season, an increase in quantity of easily available nutrients, with an improvement of the metabolic efficiency of soil microflora coupled with a more marked activity of total hydrolase and phosphatases. The variations of the parameters related to the soil microflora were strongly influenced by the seasonal climatic trend.