Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

A study on the stability of superconducting YBa2Cu3O7−x phase

The thermal stability of the superconducting phase of nominal composition YBa₂Cu₃O_7–x -sintered pellets has been studied with respect to different temperatures (ranging from 300 to 950° C), time (ranging from 1 to 72 h), oxygen partial pressure (from 4 Pa to 1 atm) and carbon dioxide partial pressure (from 10^–4 Pa to 1 atm). Annealed samples were characterized by X-ray diffraction analysis, optical microscopy, and resistive measurements of the superconductive transition temperature. A stability field of the orthorhombic and tetragonal phases was obtained, showing a region of coexistance. The decomposition of the 1 2 3 phase is found to be strongly influenced by the presence of a small amount of CO₂ (1 p.p.m.) in the sintering atmosphere. A sintering process is proposed to avoid the formation of by-products.     

A study of the use of COSMO-SkyMed SAR PingPong polarimetric mode for rice growth monitoring

The sensitivity of COSMO-SkyMed (CSK) incoherent dual-polarimetric synthetic aperture radar (SAR) data to the rice growth cycle is investigated here. State-of-the-art scattering models are used, together with a time series of 24 CSK SAR images collected in Mekong Delta, Vietnam in 2014, to interpret the behaviour of multi-polarization features with respect to the different phenological stages that characterize rice growth. Experimental results show the multi-polarization features sensitivity with respect to rice growth cycle and witness that a joint use of the co-polarized channels (i.e. co-polarized ratio or correlation between co-polarized channels) allows identifying scattering behaviours that are compatible with four stages of the rice growth cycle.     

The SATIN Component System-A Metamodel for Engineering Adaptable Mobile Systems

Mobile computing devices, such as personal digital assistants and mobile phones, are becoming increasingly popular, smaller, and more capable. We argue that mobile systems should be able to adapt to changing requirements and execution environments. Adaptation requires the ability-to reconfigure the deployed code base on a mobile device. Such reconfiguration is considerably simplified if mobile applications are component-oriented rather than monolithic blocks of code. We present the SATIN (system adaptation targeting integrated networks) component metamodel, a lightweight local component metamodel that offers the flexible use of logical mobility primitives to reconfigure the software system by dynamically transferring code. The metamodel is implemented in the SATIN middleware system, a component-based mobile computing middleware that uses the mobility primitives defined in the metamodel to reconfigure both itself and applications that it hosts. We demonstrate the suitability of SATIN in terms of lightweightedness, flexibility, and reusability for the creation of adaptable mobile systems by using it to implement, port, and evaluate a number of existing and new applications, including an active network platform developed for satellite communication at the European space agency. These applications exhibit different aspects of adaptation and demonstrate the flexibility of the approach and the advantages gained     

By-products formation during degradation of isoproturon in aqueous solution. II: Chlorination

After a previous study in which the considered oxidant was ozone (Part I), a laboratory investigation has been carried out to study the degradation of the herbicide isoproturon during its reaction with another oxidant, i.e. chlorine, in aqueous solution (Part II; this paper). The specific aim was to identify the by-products formed. The effects of pH and the presence of bromide ions were studied. Reactions have been carried out at room temperature, in phosphate buffered aqueous solutions, at four pHs (6, 7, 8 and 9). By-products identification was first performed using relatively high initial reagent concentrations which were analytically convenient ([isoproturon] = 40 mg/l, [HClO + ClO-] = 160 mg Cl/l, [Br-] = 80 mg/l). In follow-up studies, the by-products identified during this preliminary step were searched for when using concentration values closer to those actually encountered at real water treatment plants ([isoproturon] = 0.4 and 0.004 mg/l, [HClO + ClO-] = 1.6 mg Cl/l, [Br-] = 0.8 and 0.008 mg/l). Under all of the studied conditions, the results showed that isoproturon is completely degraded and that it decays much faster in the presence of bromide. The pH has a negligible influence when bromide ions are absent. On the contrary, if bromide ions are present, the isoproturon decay is slower at higher pH values. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analyses have led to the identification of several by-products as a result of simultaneous oxidation and substitution reactions, both occurring on the aromatic ring of the herbicide. However, the more abundant by-products are those resulting from the oxidation of the isoproturon aromatic ring. As far as halogenated by-products are concerned, the higher the bromide ion concentration the higher the ratio of brominated to chlorinated by-products. On the basis of the analytical results, a pathway for isoproturon degradation under the studied conditions is proposed.     

Data driven analysis of functional brain networks in fMRI for schizophrenia investigation

The purpose of this article is to present a methodology to identify the sources of activity in brain networks from functional magnetic resonance imaging (fMRI) data using the multiset canonical correlation analysis algorithm. The aim is to lay the foundations for a screening marker to be used as indicator of mental diseases. Group analysis blind source separation methods have proved reliable to extract the latent sources underlying the brain activities but currently there is no recognized biomarker for mental disorders. Recent studies have identified alterations in the so called default mode network (DMN) that are common to several neuropsychiatric disorders, including schizophrenia. In particular, here we account for the hypothesis that the alterations in the DMN activity can be effectively highlighted by analyzing the transient states between two different tasks. A set of fMRI data acquired from 18 subjects performing working memory tasks is investigated for such purpose. Subjects are patients affected by schizophrenia for one half and healthy control subjects for the other. Under these conditions, the proposed methodology provides high discrimination performances in terms of classification error, thereby providing promising results for a preliminary tool able to monitor the disease state or to perform a prescreening for patients at risk for schizophrenia. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 239–248, 2014     

Hierarchically Structured Magnetic Nanoconstructs with Enhanced Relaxivity and Cooperative Tumor Accumulation

Iron oxide nanoparticles are formidable multifunctional systems capable of contrast enhancement in magnetic resonance imaging, guidance under remote fields, heat generation, and biodegradation. Yet, this potential is underutilized in that each function manifests at different nanoparticle sizes. Here, sub‐micrometer discoidal magnetic nanoconstructs are realized by confining 5 nm ultra‐small super‐paramagnetic iron oxide nanoparticles (USPIOs) within two different mesoporous structures, made out of silicon and polymers. These nanoconstructs exhibit transversal relaxivities up to ≈10 times (r ₂ ≈ 835 mm ^?1 s^?1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r ₂ relaxivity arises from the formation of mesoscopic USPIO clusters within the porous matrix, inducing a local reduction in water molecule mobility as demonstrated via molecular dynamics simulations. The cooperative accumulation under static magnetic field derives from the large amount of iron that can be loaded per nanoconstuct (up to ≈65 fg) and the consequential generation of significant inter‐particle magnetic dipole interactions. In tumor bearing mice, the silicon‐based nanoconstructs provide MRI contrast enhancement at much smaller doses of iron (≈0.5 mg of Fe kg^?1 animal) as compared to current practice.     

NG-nitro-L-arginine methyl ester reduces senna- and cascara-induced diarrhoea and fluid secretion in the rat

Senna (60 mg/kg orally) and cascara (800 mg/kg orally)-induced diarrhoea and net fluid secretion were studied in rats for a time period of 1-8 h. NG-Nitro-L-arginine methyl ester (L-NAME) (2.5-25 mg/kg i.p. twice, 15 min before and 4 h after laxative administration), an inhibitor of nitric oxide synthase, reduced the diarrhoeal response. This effect was counteracted by L-arginine (600 and 1500 mg/kg i.p. 15 min before laxative administration), the precursor of nitric oxide (NO). The senna- and cascara-stimulated fluid secretion was reduced by NG-nitro-L-arginine methyl ester 25 mg/kg i.p. (twice, 15 min before and 4 h after laxative administration), while the stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) 25 mg/kg i.p. was without effect. These results suggest a possible involvement of NO in senna- and cascara-induced diarrhoea and fluid secretion.