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 dynamic linear programming approach to market allocation of renewable resources in the italian energy system: The case of solar thermal and biogas technologies

In Italy solar thermal energy and energy from biogas are two possible means of reducing dependence on energy imports. Using a multiperiod LP model (MARKAL) the authors assessed the likely potential of both technologies under various circumstances. The study covered the period 1980–2005, in five segments of five years. It focused only on the subsystem of the energy end-uses which can be substituted for by solar thermal and biogas technologies. The overall non-renewable sources which can be saved in 20 years by these technologies total 450 PJ (1 PJ = 10^{1 5} J) if the fuel prices rise at 0 per cent average annual, 1450 PJ if the fuel prices rise at 4.2 per cent average annual, 1860 PJ if the fuel prices rise at 7.2 per cent average annual and 3780 PJ if the fuel prices rise at 15 per cent average annual. However the most competitive technologies appear to be solar water heaters used mainly in the private and commercial sectors and biogas systems used mainly in the agricultural sector. The study was carried out by APRE under ENEA (formerly CNEN) contract and was intended to serve as an analytical basis for establishing an overall development and demonstration strategy for end-use renewable technologies in Italy.     

A light intensity function suitable for multimode fiber-opticsensors

Intensity distribution functions on the image plane are derived under the assumption that a multimode optic fiber is illuminated by a light source which can be approximated by infinite uniangular beams carrying equal power. The application of the theory to a Lambertian source is discussed. Experimental results, based on the observation of the light intensity distribution imaged on an opaque screen and collected by a digital camera, are presented. The theoretical and experimental data are compared to verify that the intensity function is an accurate model for describing the realistic approach to sensor design. The limitations of the uniangular and uniform intensity distribution models are discussed on the basis of theoretical and experimental results     

Radio resource sharing for ad hoc networking with UWB

Ultra-wideband (UWB) radio is becoming a promising field for new generation's digital communication systems. This technique, based mainly on the impulse radio paradigm, offers great flexibility and shows enormous potential in view of a future broadband wireless access. We present the main principles to design a multiaccess scheme based on UWB. The potential of UWB is exploited within a distributed ad hoc wireless system, where we describe the principles for the definition of a medium-access control (MAC) for mobile computing applications and we analyze the main performance results derived from simulations. A general framework for radio resource sharing is outlined for classes of traffic requiring both elastic-dynamic and guaranteed-reserved bandwidth. Then, we discuss the issue of supporting the proposed radio resource sharing scheme by means of a distributed MAC protocol.     

A Model of Weekly Labor Participation for a Belgian Synthetic Population

This paper presents a model of labor participation calibrated on a weekly basis; part-time and full-time employments are also considered. By applying the theory of random utility maximization we model households’ choices. In order to have a good temporal and spatial coverage the model is calibrated on three datasets, extracted from both national and regional travel surveys. The results are applied to synthetic households that reproduce the Belgian population. The proposed innovative methodology simulates synthetic agents by accounting both for households’ and individuals’ characteristics, while not suffering from the problem of the “zero cell value”. The results indicate that there is major day-to-day variability in working activity participation; in particular, on Wednesdays and Fridays the number of households working part-time or not working is particularly high. This is consistent with what was expected by the analysts. Working participation is a fundamental component in activity based models where work is considered a skeletal activity. The tools developed here can be useful to study how changes in population characteristics (i.e. increases of flexible working arrangements and of the number of women in the work force) affect activity participation and travel patterns.     

The GAUGAA Motif Is Responsible for the Binding between circSMARCA5 and SRSF1 and Related Downstream Effects on Glioblastoma Multiforme Cell Migration and Angiogenic Potential

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Role of anionic and nonionic surfactants on the control of particle size and latex colloidal stability in the seeded emulsion polymerization of butyl methacrylate

The evolution of the main colloidal parameters in the seeded starved‐feed semi‐continuous emulsion polymerization of butyl methacrylate (BMA) was investigated, with the main purpose of assessing the effectiveness of the semi‐empirical relationship S = K · S_S · ΔA/A_S as a tool to define the surfactant/monomer feed ratio (∝ K) best suited to achieve a target particle size. In particular, the effect of the type and amount of surfactant [i.e., anionic, sodium dodecyl sulfate (SDS), or nonionic, Brij 58P] added during the semi‐continuous stage was considered. Coagulum formation was never observed under the adopted experimental conditions. To detect the occurrence of secondary nucleation or particle aggregation, or both, the particle size and number of particles, the surface tension and the particle surface coverage ratio were correlated. The best results were obtained with SDS and 0.8 ≤ K ≤ 3. In fact, under the selected experimental conditions, only with SDS did the number of particles remain nearly constant throughout the polymerization at the value defined by the seed latex; the particle size distribution was highly monodisperse, and the final particle diameter closely matched the calculated one (～ 120 nm). The above semi‐empirical relationship based on the adjustable parameter K was validated by running test polymerizations aimed at lattices with well‐defined particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3083–3094, 2006