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Garcinoic acid (GA or delta-T3-13'COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in beta-amyloid (Abeta) metabolism and progression of Alzheimer's disease (AD). In this study, we investigated GA's effects on Abeta oligomer formation and deposition. Specifically, we compared them with those of other vitamin E analogs and the soy isoflavone genistein, a natural agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) that has therapeutic potential for managing AD. GA significantly reduced Abeta aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARgamma expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable to that of its metabolic precursor delta-tocotrienol and higher than those of alpha-tocopherol metabolites. Unlike for genistein and the other vitamin E compounds, the GA-induced restoration of ApoE efflux was not affected by pharmacological inhibition of PPARgamma activity, and specific activation of pregnane X receptor (PXR) was observed together with ApoE and multidrug resistance protein 1 (MDR1) membrane transporter up-regulation in both the mouse astrocytes and brain tissue. These effects of GA were associated with reduced Abeta deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Abeta oligomerization and deposition in the brain. The mechanistic aspects of GA's properties appear to be distinct from those of other vitamin E metabolites and of genistein. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

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Il glifosate rappresenta il principale strumento per il controllo delle infestanti nei fruttiferi, ma il suo utilizzo esclusivo ha determinato la selezione delle specie meno suscettibili e di infestanti resistenti. Inoltre sono stati sollevati allarmi sulla presunta tossicità e pericolosità ambientale, quindi è stato auspicato da molti la riduzione dell'uso di questa molecola. Nel presente testo sono descritti i possibili erbicidi alternativi ed i metodi di controllo non-chimici evidenziandone le caratteristiche e le limitazioni tecniche. Una strategia di diserbo alternativa deve basarsi sull'integrazione di erbicidi residuali e di post-emergenza, con distribuzione limitata alla fila della coltura per ridurre l'impatto ambientale. Gli unici strumenti non chimici efficaci disponibili sono le lavorazioni superficiali o trinciature/sfalci. Questo tipo di gestione non è però fattibile nei frutteti o vigneti ad alta densità. La sostituzione del glifosate comporta un maggiore carico di lavoro e un inevitabile aumento di costi e richiede una maggiore competenza e attenzione da parte dei tecnici che dovranno stabilire uno specifico piano di gestione in base alle infestanti presenti.

In Italy, rainfall induced shallow landslides are frequent phenomena that cause casualties every year. At the national and regional scales, empirical rainfall thresholds can predict the occurrence of single or multiple rainfall-induced shallow landslides. In this work, we updated a historical catalogue listing 553 rainfall events that triggered 723 landslides in the Abruzzo, Marche and Umbria regions, central Italy, between February 2002 and March 2011. For each event, the rainfall duration (D) and the cumulated event rainfall (E) responsible for the failure are known, together with the exact or approximate location of the landslide. To analyse the influence of topography and soil characteristics on the occurrence of rainfall induced shallow landslides, we subdivided the study area in three topographic divisions, and eight soil domains. We analysed the (D, E) rainfall conditions that resulted in the documented shallow landslides in each topographic division and regional soil domain, and we defined ED rainfall thresholds at 5 % exceedance probability level for the two subdivisions. We expect that the new topographic and pedological thresholds will contribute to forecast shallow landslides in central Italy, and in areas characterized by similar morphological and soil settings.

Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis.Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice.CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules.This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy.

Objective: Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above. Design: Data were obtained on a large group of children followed longitudinally in trials and cohort studies in Europe and the USA. Follow-up was censored 6 months after the start of any antiretroviral drug other than zidovudine monotherapy. Methods: Discordance between CD4 cell count and percentage was defined in relation to ART initiation thresholds in World Health Organization (WHO) and European paediatric treatment guidelines. The relative prognostic value of CD4 cell count and percentage for progression to AIDS/death was investigated using time-updated Cox proportional hazards models, stratified by age. Results: Among 3345 children, with a total of 21 815 pairs of CD4 measurements analysed, 980 developed AIDS and/or died after a median follow-up of 1.7 years. Over one-half of children had discordant values of CD4 cell markers at the first visit when one or both treatment thresholds were crossed and approximately one-third had the same pattern of discordance at a subsequent measurement. Models suggested that CD4 percentage had little or no prognostic value over and above that contained in CD4 cell count, irrespective of age. Conclusions: More emphasis should be placed on CD4 cell count than on CD4 percentage in deciding when to start ART in HIV-1-infected children. (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Models simulating water and sediment fluxes in more or less complicated landscapes are now many. A recent paper (Merritt et al., 2003) reviews 17 models on the basis of their being physically or empirically based, on inputs and outputs, model structure, runoff, erosion/transport and nutrient modelling, predictive accuracy/limitations. This review, despite its length, barely surfs the now fairly crowded universe of model. It shows some inevitable inaccuracy (e.g. LISEM, differentely from what reported there, describes gully generation, deposition and transport in land) which is certainly due to the continuous rewriting and updating of some of the most recent models. In any case, only models that have been used and possibly examined in their inner details (i.e., their codes) can be properly discussed, criticized and their limits defined. Generally, the manuals that are distributed with the models are not sufficiently informative for such a task.

Soil erosion is a complex process thath dipends on climate, relief, soil and vegetation.