ESPRESSIONE DI PROTEINE COINVOLTE NEL TRASPORTO PLACENTARE DEL FERRO IN GRAVIDANZE NORMALI E PATOLOGICHE

Background Intrauterine Growth Restriction (IUGR) and Pre-eclampsia (PE) are pregnancy pathologies associated with deficient placental function, leading to decreased nutrient and oxygen availability to the fetus. Iron (Fe) deficiency in pregnancy is associated with low birth weight and premature delivery. Nevertheless, Fe oversupply promotes the generation of free radicals and causes oxidative damage in the cells. A previous study performed in the lab where this thesis has been carried out demonstrated a significant decrease of the Fe cell-importer Transferrin Receptor (TfR1), located in the trophoblast cell (TC) microvillar membrane, in human Intrauterine Growth Restricted (IUGR) vs normal (N) placentas (Mand\uf2 C. et al. 2011). Ferroportin (FPN) is a trans-membrane protein located in the TC basal membrane that exports Fe towards the fetal circulation. Aim We hypothesized that TfR1 downregulation in IUGR placentas may be due to Fe intracellular accumulation. Thus, we measured FPN gene and protein expression in human IUGR vs N placentas. Then, we extended the Fe transporters investigation to PE placentas, by measuring TfR1 and FPN gene expression in human PE and PE associated with IUGR vs N placentas. Furthermore, we evaluated the relationship between Fe supplementation, food intake, haematologic parameters and pregnancy outcome in a cohort of Italian pregnant and healthy women. Materials and Methods Placentas were sampled at the time of elective cesarean section; villi were selected, washed and immediately frozen for following analysis. Umbilical venous and arterial blood was sampled for pH, oxygen measurements, Hb and lactate measurements, from a doubly clamped segment of the cord immediately after fetal extraction. All samples were collected in hepa- rinized syringes and kept on ice until the end of analysis. All the parameters were measured on a GEM Premier 3000 (Instrumentation Laboratory). FPN mRNA was quantified in a total of 50 N, 41 IUGR, 10 PE and 15 PE+IUGR placentas by Real Time PCR and FPN protein expression was quantified in 26 N and 14 IUGR by Enzyme-Linked ImmunoSorbent Assay. TfR1 mRNA was quantified in 28 N, 10 PE and 15 PE+IUGR placentas. For the study of Fe supplementation, 55 healthy Italian singleton pregnant women were randomized in 4 groups in relation to different doses and types of Fe supplementation (Controls, Fe Sulphate 30 mg, Fe liposomial 14 mg and Fe liposomial 28 mg). At 28-30 gestational weeks data about eating behavior were collected by food frequency questionnaires and hematologic parameters of Fe content (hemoglobin, ferritin, transferrin, serum Fe, folate, vitamin B12, homocystein) in maternal blood by biochemical analysis. Results and Discussion Fetuses from IUGR pregnancies, both with and without PE, have lower pO2 in umbilical vein, while there were no significant differences in fetal emoglobin (Hb) among controls, IUGR, PE and PE+IUGR groups. Both FPN mRNA and protein expression were not statistically different in IUGR compared to N placentas. FPN and TfR1 mRNA levels were not statistically different in PE and in PE+IUGR compared to N placentas. Our results showed no differences in FPN mRNA and protein placental levels between IUGR and N. This suggests that the Fe reaching IUGR fetuses may be decreased compared to normal pregnancies, as a consequence of TfR1 downregulation in the microvillar membranes. This could impair many cellular processes, since Fe is a very important element for enzyme functions and for a correct oxidative status in the cell. TfR1 and FPN mRNA levels were not statistically different in PE and in PE+IUGR vs. N placentas, suggesting that Fe transport is not affected in Preeclampsia. However, we aim at enlarging our analysis to reach definitive conclusions on the Fe transport system in PE placentas. No significant differences were found in the maternal hematologic parameters between the 4 groups of randomized pregnant women at 28-31 weeks, with the exception of hemoglobin, which was significantly higher in women supplemented with 28 mg of Fe liposomial compared to controls (p<0.01). The groups were homogeneous in relation to pregnancy outcomes: no differences were found in neonatal and placental weights, as well as in gestational age at delivery and in umbilical artery pH. The food frequency questionnaires analysis revealed that the control group assumed higher quantity of bioavailable iron (meat) compared to other groups. This may explain the absence of significant differences in the maternal iron status in the control group compared to the supplemented groups

Active systems based on silver-montmorillonite nanoparticles embedded into bio-based polymer matrices for packaging applications.

Silver-montmorillonite (Ag-MMT) antimicrobial nanoparticles were obtained by allowing silver ions from nitrate solutions to replace the Na(+) of natural montmorillonite and to be reduced by thermal treatment. The Ag-MMT nanoparticles were embedded in agar, zein, and poly(ε-caprolactone) polymer matrices. These nanocomposites were tested in vitro with a three-strain cocktail of Pseudomonas spp. to assess antimicrobial effectiveness. The results indicate that Ag-MMT nanoparticles embedded into agar may have antimicrobial activity against selected spoilage microorganisms. No antimicrobial effects were recorded with active zein and poly(ε-caprolactone). The water content of the polymeric matrix was the key parameter associated with antimicrobial effectiveness of this active system intended for food packaging applications

JZL184, a monoacylglycerol lipase inhibitor, induces bone loss in a multiple myeloma model of immunocompetent mice

Multiple myeloma (MM) patients develop osteolysis characterised by excessive osteoclastic bone destruction and lack of osteoblast bone formation. Pharmacological manipulation of monoacylglycerol lipase (MAGL), an enzyme responsible for the degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced skeletal tumour burden and osteolysis associated with osteosarcoma and advanced breast and prostate cancers. MM and hematopoietic, immune and bone marrow cells express high levels of type 2 cannabinoid receptor and osteoblasts secrete 2-AG. However, the effects of MAGL manipulation on MM have not been investigated. Here, we report that treatment of pre-osteoclasts with non-cytotoxic concentrations of JZL184, a verified MAGL inhibitor, enhanced MM- and RANKL-induced osteoclast formation and size in vitro. Exposure of osteoblasts to JZL184 in the presence of MM cell-derived factors reduced osteoblast growth but had no effect on the ability of these cells to mature or form bone nodules. In vivo, administration of JZL184 induced a modest, yet significant, bone loss at both trabecular and cortical compartments of long bones of immunocompetent mice inoculated with the syngeneic 5TGM1-GFP MM cells. Notably, JZL184 failed to inhibit the in vitro growth of a panel of mouse and human MM cell lines, or reduce tumour burden in mice. Thus, MAGL inhibitors such as JZL184 can exacerbate MM-induced bone loss

N=1 Superpotentials from Multi-Instanton Calculus

In this paper we compute gaugino and scalar condensates in N=1 supersymmetric gauge theories with and without massive adjoint matter, using localization formulae over the multi--instanton moduli space. Furthermore we compute the chiral ring relations among the correlators of the $N=1^*$ theory and check this result against the multi-instanton computation finding agreement.Comment: 31 pages, uses youngtab.sty, some explanations added, version to appear in JHE

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure

Modelo de distribución de agua en suelo regado por goteo

[ES] Se desarrolla un modelo de simulación de la dinámica del agua en el suelo en riego localizado, denominado SIMDAS. Para el desarrollo del procedimiento numérico, se utiliza la teoría de flujo de agua en condiciones de no saturación, sin efecto histerético, resolviendo la ecuación de flujo axisimétrico sin y con extracción de agua por la planta a partir de un método en diferencias finitas, con la consideración de los distintos horizontes del suelo. Verificado el modelo en campo, los resultados que presenta son satisfactorios cuando no se contempla la presencia de cultivo, pero no lo son cuando interviene la extracción de agua por la planta. Por consiguiente, el grado de aceptabilidad es suficiente para fines de diseño agronómico de sistemas de riego localizado, pero no lo es para aquellos casos en que la extracción de agua por la planta interviene de manera destacada, como en el manejo y la programación de riegos.Ramírez De Cartagena Bisbe, F.; Sáinz Sánchez, MA. (1997). Modelo de distribución de agua en suelo regado por goteo. Ingeniería del Agua. 4(1):57-70. https://doi.org/10.4995/ia.1997.2716SWORD577041Armstrong C.F., Wilson T.V. (1983) Computer model for moisture distribution in stratified soils under a trickle source. Transactions of the American Society of Agricultural Engineers: 1704-1709.Belmans C., Wesswling J.G., Feddes R.A. (1983) Simulation model of the water balance of a cropped soil: SWATRE. Journal of Hidrology. 63 & 21: 271-286.Ben-Asher J., Charach CH., Zemel A. (1986) Infiltration and water extraction from trickle irrigation source: The effective hemisphere model. Soil Science Society of America Journal. 50: 882-887.Brandt A., BreslerE., Diner N., Ben-Asher J., Heller J., Goldberg. (1971) Infiltration from a trickle source: I. Mathematical models. Soil Science Society of America Proceedings, 35: 675-682.Bresler R E. (1975) Two-dimensional transport of solutes during nonsteady infiltration from a trickle source. Soil Science Society of America Proceedings, 39: 604-613.Feddes R.A., Kowalik P.J., Zaradny H. (1978) Simulation of field water use and crop yield. PUDOC, Wageningen. 189pp.Ghali S.G. (1986) Mathematical modelling of soil moisture dynamics in trickle irrigated fields. Thesis, University of Southampton (UK).Gupta S.C., Larson W.E. (1979) Estimating soil wáter retention characteristics from particle size distribution, organic matter percent, and bulk density. Water Resources Research, 15(6): 1633-1635.Hillel D. (1977) Computer simulation of soil-waters dynamics. A compendium of recent work. IDRC, Ottawa, Canada. 214 pp.Jackson R.D. (1972) On the calculation of hydraulic conductivity. Soil Science Society of America Proceedings. 36: 380-382.Keller J. (1978) Trickle irrigation. In Irrigation (Ch. 7). National Engineering Handbook USDA-SCS.Keller J., Karmelid. (1975) Trickle irrigation design. Rain Bird Corp. Glendora, California USA. 133 pp.Khatri K.C. (1984) Simulation of soil moisture migration from a point source. Thesis, McGill University, Quebec, Canada.Kunze R.J., Uehara G., Graham K. (1968) Factors important in the calculation of hydraulic conductivity. Soil Science Soc. Amer. Proc., 32: 760-765.Lafolie F., Guenelon R., Van Genuchten M.TH. (1989a.) Analysis of water flow under trickle irrigation: I. Theory and numerical solution. Soil Science Society of America Journal, 53: 1310-1318.Lafolie P., Guenelon R., Van Genuchten M.TH. (1989b.) Analysis of water flow under trickle irrigation: II. Experimental evaluation. Soil Science Society of America Journal. 53: 1318-1323.Marino M.A., Tracy J.C. (1988) Flow of water through root-soil environment. Journal of Irrigation and Drainage Engineering, 114 (4): 588-604.Marshall T.J. (1958) A relation between permeability and size distribution of pores. Journal of Soil Science, 9 (8): 1-8.Millington R.J., Quirk J.P. (1959) Permeability of porous media Nature, 183: 378-388.Molz F.J., Remson I. (1970) Extraction term models of soil moisture use by transpiring plants. Water Resources Research, 6 (5): 1346-1356.Philip J.R. (1971) General theorem on steady infiltration from surface sources, with application to point and line sources. Soil Science Society of America Proceedings, 35: 867-871.Pradad R. (1988) A linear root water uptake model Journal of Hidrology, 99: 297-306.Raats P.A.C. (1977) Laterally confined, steady flows of water from sources and to sinks in unsaturated soils. Soil Science Society of America Journal, 41:294-304.Ramírez De Cartagena F. (1994) Simulación numerica de la dinámica del agua en el suelo. Aplicacion al diseño de sistemas de riego LAF. Tesis Doctoral. ETSEA. Universidad de Lleida.Rawls W.J., Brakensiek D.L. (1982) Estimating soil water retention from soil properties. Journal of the Irrigation and Drainage Division, Proc. of the ASCE, 108, IR2: 166-171.Saxton K.E., Rawls W.J., Romberger J.S., Papendick R.I. (1986) Estimating generalized soil-water characteristics from texture. Soil Science Society of America Journal, 50: 1031-1036.Taghavi S.A., Mariño M.A., Rolston D.E. (1985) Infiltration from a trickle source in a heterogeneous soil medium. Journal of Hidrology, 78: 107-121.Van Der Ploeg R.R., Benecke P. (1974) Unsteady, unsaturated, n-dimensional moisture flow in soil: A computer simulation program. Soil Science Society of America Proceedings, 38: 881-885Vermeiren L., Jobling G.A. (1986) Riego localizado. Estudios FAO Riego y Drenaje, n°36. FAO. Roma. 203 pp.Warrick A.W., Lomen D.O., Amoozegarfard A. (1980) Linearized moisture flow with root extraction for three dimensional, steady conditions. Soil Science Society of America Journal, 44: 911-914

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure