Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors

© 1998 Society for NeuroscienceATP analogs substituted in the γ-phosphorus (ATPγS, β, γ-imido-ATP, and β, γ-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices. ATP and γ-substituted analogs were equipotent to inhibit synaptic transmission in CA1 pyramid synapses (IC50 of 17–22 μM). The inhibitory effect of ATP and γ-phosphorus-substituted ATP analogs (30 μM) was not modified by the P2 receptor antagonist suramin (100 μM), was inhibited by 42–49% by the ecto-5’- nucleotidase inhibitor and α, β-methylene ADP (100 μM), was inhibited by 74–85% by 2 U/ml adenosine deaminase (which converts adenosine into its inactive metabolite-inosine), and was nearly prevented by the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 nM). Stronger support for the involvement of extracellular adenosine formation as a main requirement for the inhibitory effect of ATP and γ-substituted ATP analogs was the observation that an inhibitor of adenosine uptake, dipyridamole (20 μM), potentiated by 92–124% the inhibitory effect of ATP and γ-substituted ATP analogs (10 μM), a potentiation similar to that obtained for 10 μM adenosine (113%). Thus, the present results indicate that inhibition by extracellular ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ectonucleotidases and channeling of the generated adenosine to adenosine A1 receptors.This work was supported by Junta Nacional de Investigação Cientifica e Tecnológica, Praxis XXI, Gulbenkian Foundation, and European Union (BIOMED 2 programme

Modelling the exposure to Cronobacter sakazakii by consumption of a cocoa-milk-based beverage processed by pulsed electric fields

peer-reviewedM.C. Pina-Pérez is grateful to CSIC for providing a DOCTOR contract linked to the INNPACTO project IPT-2011-1724-060000. This study was carried out with funds from BISOSTAD project PSE-060000-2009-003, Generalitat Valenciana I+D+I emergent research groups GV/2010/064 and CYCIT project AGL2010-22206-C02-01.Infants’ exposure (Nf ) to Cronobacter sakazakii via the consumption of infant-rich-inpolyphenols cocoa-milk-based beverages (CCX-M) treated with high-intensity pulsed electric fields (PEF) was evaluated. Monte Carlo simulation enabled the prediction of the variability in C. sakazakii load in beverages at the time of consumption to be estimated. Different scenarios (initial contamination levels; PEF treatment conditions; and time-temperature combinations of CCX-M beverages storage after treatment) were simulated. Cocoa addition and PEF treatment resulted in the most influential input factors to control bacterial final load. Cronobacter spp. exposure risk was reduced by a maximum of 100 times at 95% of iterations due to addition of cocoa at 5 g/100 mL, corresponding to scenario 3 (PEF: 15 kV/cm–3,000 μs; storage 120 h at 8 °C). Moreover, the probability of illness for a healthy population was reduced from 2.15 × 10-8, in the baseline scenario, to 4.78 × 10-10 due to cocoa addition and application of 15 kV/cm–3,000 μs PEF treatment.BISOSTAD projec

Targeting the eIF4A RNA helicase blocks translation of the MUC1-C oncoprotein

The oncogenic MUC1-C subunit is aberrantly overexpressed in most human breast cancers by mechanisms that are not well understood. The present studies demonstrate that stimulation of non- malignant MCF-10A cells with epidermal growth factor (EGF) or heregulin (HRG) results in marked upregulation of MUC1-C translation. Growth factor-induced MUC1-C translation was found to be mediated by PI3K->AKT, and not MEK->ERK1/2, signaling. We also show that activation of the mTORC1->S6K1 pathway decreases PDCD4, an inhibitor of the eIF4A RNA helicase, and contributes to the induction of MUC1-C translation. In concert with these results, treatment of growth factor-stimulated MCF-10A cells with the eIF4A RNA helicase inhibitors, silvestrol and CR-1-31-B, blocked increases in MUC1-C abundance. The functional significance of the increase in MUC1-C translation is supported by the demonstration that MUC1-C, in turn, forms complexes with EGFR and promotes EGFR-mediated activation of the PI3K->AKT pathway and the induction of growth. Compared to MCF-10A cells, constitutive overexpression of MUC1-C in breast cancer cells was unaffected by EGF stimulation, but was blocked by inhibiting PI3K->AKT signaling. The overexpression of MUC1-C in breast cancer cells was also inhibited by blocking eIF4A RNA helicase activity with silvestrol and CR-1-31-B. These findings indicate that EGF-induced MUC1-C expression is mediated by the PI3K->AKT pathway and the eIF4A RNA helicase, and that this response promotes EGFR signaling in an autoinductive loop. The findings also indicate that targeting the eIF4A RNA helicase is a novel approach for blocking MUC1-C overexpression in breast cancer cells.P50 CA100707 - NCI NIH HHS; R01 CA042802 - NCI NIH HHS; R01 CA097098 - NCI NIH HHS; R01 GM073855 - NIGMS NIH HH

Using full-scale duckweed ponds as the finish stage for swine waste treatment with a focus on organic matter degradation

Artigo Publicado em: IWA - Water Science & TechnologyThe rapid increase in the number of swine has caused pronounced environmental impacts worldwide, especially on water resources. As an aggregate, smallholdings have an important role in South American pork production, contributing to the net diffusion of pollution. Thus, duckweed ponds have been successfully used for swine waste polishing, mainly for nutrient removal. Few studies have been carried out to assess organic matter degradation in duckweed ponds. Hence, the present study evaluated the efficiency of two full-scale duckweed ponds for organic matter reduction of swine waste on small pig farms. Duckweed ponds, in series, received the effluent after an anaerobic biodigester and storage pond, with a flow rate of 1 m3 day 1. After 1 year of monitoring, an improvement in effluent quality was observed, with a reduction in biochemical oxygen demand (BOD) and total chemical oxygen demand (tCOD), respectively, of 94.8 and 96.7%, operating at a loading rate of approximately 27 kgBOD ha 1 day 1 and 131 kgCOD ha 1 day 1. Algae inhibition due to duckweed coverage was strongly observed in the pond effluent, where chlorophyll a and turbidity remained below 25 μg L 1 and 10 NTU. Using the study conditions described herein, duckweed ponds were shown to be a suitable technology for swine waste treatment, contributing to the environmental sustainability of rural areas

Dissipative vortex solitons in 2D-lattices

We report the existence of stable symmetric vortex-type solutions for two-dimensional nonlinear discrete dissipative systems governed by a cubic-quintic complex Ginzburg-Landau equation. We construct a whole family of vortex solitons with a topological charge S = 1. Surprisingly, the dynamical evolution of unstable solutions of this family does not alter significantly their profile, instead their phase distribution completely changes. They transform into two-charges swirl-vortex solitons. We dynamically excite this novel structure showing its experimental feasibility.Comment: 4 pages, 20 figure