Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism

We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For this, we generate synthetic metabolic profiles for benchmarking purposes based on a well-established model for red blood cell metabolism. A variety of data sets is generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and temporal dynamics. These data sets are made available online. We apply ARACNE, a mainstream transcriptional networks reverse engineering algorithm, to these data sets and observe performance comparable to that obtained in the transcriptional domain, for which the algorithm was originally designed.Comment: 14 pages, 3 figures. Presented at the DIMACS Workshop on Dialogue on Reverse Engineering Assessment and Methods (DREAM), Sep 200

Age and Depositional Environment of Whale-Bearing Sedimentary Succession from the Lower Pliocene of Tuscany (Italy): Insights from Palaeomagnetism, Calcareous Microfossils and Facies Analyses

A c. 31 m thick section straddling the fossil find of an Early Pliocene baleen whale ("Brunella", hereafter), made in 2007 in the sedimentary fill of the Middle Ombrone Basin of Tuscany, is investigated for depositional age and environment combining palaeomagnetic, micropalaeontological (Foraminifera and calcareous nannofossils) and sedimentary facies analyses. Resting unconformably onto Late Miocene continental deposits, the Early Pliocene marine deposits include, from bottom to top, a coarse-grained wave-winnowing lag, the few metres-thick fossiliferous sandstone bedset from which Brunella was unearthed, and several metres of clays. The stratigraphic organisation of these deposits indicate deposition in a deepening upward inner shelf environment. Successful isolation of characteristic remanent magnetisation and calcareous nannofossil content indicate the investigated marine section was deposited during the interval of polarity Chron C3n.2n corresponding to the basal part of the Mediterranean nannofossil zone MNN13 (between Helicosphaera sellii Base common and the Amaurolithus primus Top) and allow estimating the depositional age of Brunella to c. 4.6 Ma. Sedimentary facies, benthic Foraminifera association and anisotropy of magnetic susceptibility characterising the deposits that embedded Brunella suggest deposition above the fair-weather base level

Potential therapeutic effects of natural heme oxygenase-1 inducers in cardiovascular diseases.

Significance: Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of α-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenols may increase the capacity of endogenous antioxidant defenses and modulate the cellular redox state. Such effects may have wide-ranging consequences for cellular growth and differentiation. Critical Issues: The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reactivity toward free radicals and their capacity to prevent the oxidation of important intracellular components. One possible protective molecular mechanism of polyphenols is nuclear factor erythroid 2-related factor (Nrf2) activation, which in turn regulates a number of detoxification enzymes. Recent Advances: Among the latter, the heme oxygenase-1 (HO-1) pathway is likely to contribute to the established and powerful antioxidant/anti-inflammatory properties of polyphenols. In this context, it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to prevention of cardiovascular diseases in various experimental models. Future Directions: The focus of this review is on the role of natural HO-1 inducers as a potential therapeutic strategy to protect the cardiovascular system against various stressors in several pathological conditions

Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model

Background: HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C. Aims: This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a "Mediterranean diet", ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an "in vitro" model of cultured hepatoma cells (HepG2). Results: plasma HDL-C levels in the population correlated negatively with myristic acid (C14:0, β = -0.24, p < 0.01), oleic acid (C18:1n9, β = -0.22, p < 0.01) and cis-11-Eicosenoic (C20:1n9, β = -0.19, p = 0.01) and positively with palmitoleic acid (C16:1, β = +0.19, p = 0.03). HepG2 cells were conditioned with FA before evaluating HDL binding kinetics, and only C14:0 increased HDL binding by a non-saturable pathway. After removal of heparan sulphate proteoglycans (HSPG) by heparinases HDL binding dropped by 29% only in C14:0 conditioned cells (p < 0.05). C14:0 showed also the highest internalization of HDL-derived cholesteryl esters (CE, +32% p = 0.01 vs. non-conditioned cells). Conclusions: C14:0 was correlated with decreased plasma HDL-C levels in a Mediterranean population. C14:0 might reduce HDL-C levels by increasing HDL trapping to cell surface HSPG and CE stripping from bound HDL. Other mechanisms are to be investigated to explain the effects of other FA on HDL metabolism

Austerity urbanism and Olympic counter-legacies: gendering, defending and expanding the urban commons in East London

This article reflects on an occupation led by single mothers to contest the destruction of social housing in post-Olympics East London. In the process, it argues for a more gendered theorisation of the urban commons. Drawing on auto-ethnography, participant observation and qualitative interviews, the article argues three central points: First, that the occupation demonstrates the gendered nature of the urban commons and the leadership of women in defending them from enclosure; second that the defence of an existing urban commons enabled the creation of a new temporary commons characterised by the collectivisation of gendered socially reproductive activities; and third that this commoning has had a lasting impact on housing activism at the city scale and beyond. This impact is conceptualised as an ‘Olympic counter-legacy’ that is characterised by the forging of new relationships and affinities, the strengthening of networked activism and circulation of tactics between campaign groups

Sustainable use of citrus waste as organic amendment in orange orchards

The use of citrus waste (peel, CW) as organic fertilizer was investigated on soil microbiota and on soil physico-chemical and hydraulic characteristics. The biotic components on CW and the effect on nutritional status, leaf chlorophyll content, fruit set and production of "Tarocco" orange trees were also identified. The citrus waste was supplied to an experimental orchard at different doses: 45 kg m(-2) (with and without Ca(OH)(2) addition) and 90 kg m(-2). The study was conducted in three consecutive years (2015-2017) on 20-year old orange trees at the experimental farm of the University of Catania (Italy). The main results of the study confirm that the use of CW as a biofertilizer offers a great opportunity for sustainable sweet orange production

Gout, allopurinol intake and clinical outcomes in the hospitalized multimorbid elderly

Background: Increased serum uric acid has been considered a cardiovascular risk factor but no study has assessed its relation with hospital mortality or length of stay. On the basis of data obtained from a prospective registry, the prevalence of gout/hyperuricemia and its association with these and other clinical parameters was evaluated in an Italian cohort of elderly patients acutely admitted to internal medicine or geriatric wards. Methods: While the prevalence of gout was calculated by counting patients with this diagnosis hyperuricemia was inferred in patients taking allopurinol at hospital admission or discharge, on the assumption that this drug was only prescribed owing to the \ufb01nding of high serum levels of uric acid. A series of clinical and demographic variables were evaluated for their association with gout/hyperuricemia. Results: Of 1380 patients, 139 (10%) had a diagnosis of gout or were prescribed allopurinol. They had more co-morbidities (7.0 vs 5.6; P b 0.0001) and consumed more drugs (6.8 vs 5.0; P b 0.0001). The CIRS (co-morbidity index) was worse in these patients (OR 1.28 95% CI 1.15\u20131.41). Multivariable regression analysis showed that only renal and heart failures were independently associated with gout/allopurinol intake. Moreover, this combined event was associated with an increased risk of adverse events during hospitalization (OR 1.66, 95% CI 1.16\u20132.36), but not with the risk of re-hospitalization, length of hospital stay or death. Conclusions: Gout/allopurinol intake has a high prevalence in elderly patients acutely admitted to hospital and are associated with renal and cardiovascular diseases, an increased rate of adverse events and a high degree of drug consumption. In contrast, this \ufb01nding did not affect the length of hospitalization nor hospital mortality

High-accuracy determination of the neutron flux in the new experimental area n_TOF-EAR2 at CERN

A new high flux experimental area has recently become operational at the n_TOF facility at CERN. This new measuring station, n_TOF-EAR2, is placed at the end of a vertical beam line at a distance of approximately 20m from the spallation target. The characterization of the neutron beam, in terms of flux, spatial profile and resolution function, is of crucial importance for the feasibility study and data analysis of all measurements to be performed in the new area. In this paper, the measurement of the neutron flux, performed with different solid-state and gaseous detection systems, and using three neutron-converting reactions considered standard in different energy regions is reported. The results of the various measurements have been combined, yielding an evaluated neutron energy distribution in a wide energy range, from 2meV to 100MeV, with an accuracy ranging from 2%, at low energy, to 6% in the high-energy region. In addition, an absolute normalization of the n_TOF-EAR2 neutron flux has been obtained by means of an activation measurement performed with 197Au foils in the beam.Peer reviewe