Interleukin-1␤ is a proinflammatory cytokine implicated under pathological conditions involving NMDA receptor activation, including the AIDS dementia complex (HAD). No information is available on the molecular mechanisms recruited by native interleukin-1␤ produced under this type of condition. Using a sandwich co-culture of primary hippocampal neurons and glia, we investigated whether native interleukin-1␤ released by HIV-gp120-activated glia (i) affects NMDAR functions and (ii) the relevance on neuronal spine density and survival, two specific traits of HAD. Increased phosphorylation of NR2B Tyr-1472 was observed after 24 h of exposure of neurons to 600 pM gp120. This effect occurred only when neurons were treated in the presence of glial cells and was abolished by the interleukin-1 receptor antagonist (IL-1ra). Gp120-induced phosphorylation of NR2B resulted in a sustained elevation of intracellular Ca 2؉ in neurons and in a significant increase of NR2B binding to PSD95. Increased intracellular Ca2؉ was prevented by 10 M ifenprodil, that selectively inhibits receptors containing the NR2B, by interleukin-1ra and by Ca-pYEEIE, a Src family SH2 inhibitor peptide. These last two inhibitors, prevented also NR2B binding to PSD95. Finally, gp120 reduced by 35% of the total PSD95 positive spine density after 48 h of treatment and induced by 30% of the neuronal death. Again, both of these effects were blocked by Ca-pYEEIE. Altogether, our data show that gp120 releasing interleukin-1␤ from glia increases tyrosine phosphorylation of NMDAR. Thus, tyrosine phosphorylation may contribute to the sensitization of the receptor increasing its function and synaptic localization. Both of these effects are relevant for neurodegeneration. Interleukin-1␤ (IL-1␤)3 has been proposed as a novel neuromodulator involved in the communication between glia and neurons (1-4), opening up new perspective in the current view of brain behavior. This cytokine, locally produced by glial cells as a consequence of CNS diseases and/or in response to neuronal activities (4), exerts a profound impact on neuronal functionality through a specific receptor. So far, IL-1␤ has been implicated in the exacerbation of neuronal damage caused by excitotoxic, ischemic, traumatic brain injury (5, 6), and viral infection (AIDS dementia complex: HAD) (7-9), in seizures (10) as well as in physiological events such as long-term potentiation (11, 12), sleep (13), memory consolidation (14, 15), and pain (16). Although IL-1␤ may offer exciting potential in the discovery of novel targets to modulate brain behavior, the biochemical pathways specifically recruited in neurons by this cytokine have not been explored in detail.Recombinant IL-1␤ potentiates calcium response and neuronal death achieved through NMDA receptor activation in primary hippocampal neurons by increasing phosphorylation of NR2B tyrosine 1472 (17). Tyrosine phosphorylation of NR2 subunits has been involved in NMDAR channel gating, protection of NR2 subunits against degradation by calpain, assembly with sig...

Abstract. Data of soil hydraulic properties forms often a limiting factor in unsaturated zone modelling, especially at the larger scales. Investigations for the hydraulic characterization of soils are time-consuming and costly, and the accuracy of the results obtained by the different methodologies is still debated. However, we may wonder how the uncertainty in soil hydraulic parameters relates to the uncertainty of the selected modelling approach. We performed an intensive monitoring study during the cropping season of a 10 ha maize field in Northern Italy. The data were used to: i) compare different methods for determining soil hydraulic parameters and ii) evaluate the effect of the uncertainty in these parameters on different variables (i.e. evapotranspiration, average water content in the root zone, flux at the bottom boundary of the root zone) simulated by two hydrological models of different complexity: SWAP, a widely used model of soil moisture dynamics in unsaturated soils based on Richards equation, and ALHyMUS, a conceptual model of the same dynamics based on a reservoir cascade scheme. We employed five direct and indirect methods to determine soil hydraulic parameters for each horizon of the experimental profile. Two methods were based on a parameter optimization of: a) laboratory measured retention and hydraulic conductivity data and b) field measured retention and hydraulic conductivity data. The remaining three methods were based on the application of widely used Pedo-Transfer Functions: c) Rawls and Brakensiek, d) HYPRES, and e) ROSETTA. Simulations were performed using meteorological, irrigation and crop data measured at the experimental site during the period June -October 2006. Results showed a wide range of soil hydraulic parameter values generated with the different Correspondence to: G. Baroni (gabriele.baroni@email.it) methods, especially for the saturated hydraulic conductivity K sat and the shape parameter α of the van Genuchten curve. This is reflected in a variability of the modeling results which is, as expected, different for each model and each variable analysed. The variability of the simulated water content in the root zone and of the bottom flux for different soil hydraulic parameter sets is found to be often larger than the difference between modeling results of the two models using the same soil hydraulic parameter set. Also we found that a good agreement in simulated soil moisture patterns may occur even if evapotranspiration and percolation fluxes are significantly different. Therefore multiple output variables should be considered to test the performances of methods and models.

No abstract

Lignan-rich whole-grain cereals, beans, berries, and nuts show protective effects against a variety of chronic diseases, including cancer. Lignans are converted by intestinal microflora to enterolactone (EL) and its oxidation product enterodiol (ED). To investigate the immunomodulatory effect of EL and ED in human cells, peripheral blood lymphocytes were treated with increasing physiologically relevant concentrations of EL and ED (0-1000 microM) and stimulated with lipopolysaccharide (LPS) and anti-CD3 plus anti-CD28 monoclonal antibodies. A dose-related inhibition of cell proliferation and cytokine production was observed, with EL being the most active. Molecular investigations in THP-1 cells showed that both EL and ED prevented inhibitory-kappaB (I-kappaB) degradation and nuclear factor-kappaB (NF-kappaB) activation, which in turn resulted in decreased tumor necrosis factor-alpha (TNF-alpha) production. EL and ED were also able to pass the intestinal barrier and modulate cytokine production. The findings of the present study reveal potential mechanisms that could explain some in vivo beneficial effects of lignans.

No abstract