Independent regulation of P53 stabilisation and activation after Rb deletion in primary epithelial cells

We have previously reported that deletion of the retinoblastoma gene Rb leads to rapid but transient p53 stabilisation. We investigated here the pathways involved. We show that upon Rb-deletion dysregulated E2F activates p19(ARF) expression that localises in the nucleoli. There it interacts with MDM2, leading to P53 stabilisation. At the same time, ATR is activated, activating CHK1 that may phosphorylate P53 but also contribute to inhibition of MnSOD expression leading to accumulation of ROS (reactive oxygen species) and subsequent DNA injury, which in turn maintains ATR/CHK1 activated. However, from 72 h after Rb deletion, NPM interacts with P19ARF and concomitantly the interaction between p19(ARF) and MDM2 decreases leading to a return to P53 degradation. This occurs despite the persistence of the DNA damage response pathways. We therefore observe in primary cells not subjected to exogenous gene expression or exogenous DNA damaging treatment, activation of 2 concomitant pathways of activation of P53 that are dealt with in independent manner: an oncogenic pathway with rapid activation of ARF which is 'switched off' downstream of p19(ARF) activation after 72 h of induction and a DNA damage response pathway keeping a low level of transcriptionally active P53 sufficient to deal with a physiological elevation of oxidative DNA injury. A possible connection between the two pathways is discussed.Publisher PDFPeer reviewe

Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFbeta cell cycle arrest

TGFbeta is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFbeta in disease. We asked how Rb-deficiency would affect responses to TGFbeta-induced cell cycle arrest.Publisher PDFPeer reviewe

The Cyclic Connectivity of Homogeneous Arcwise Connected Continua

A continuum is cyclicly connected provided each pair of its points lie together on some simple closed curve. In 1927, G. T. Whyburn proved that a locally connected plane continuum is cyclicly connected if and only if it contains no separating points. This theorem was fundamental in his original treatment of cyclic element theory. Since then numerous authors have obtained extensions of Whyburn\u27s theorem. In this paper we characterize cyclic connectedness in the class of all Hausdorff continua

Cranberry field rot, storage rot, fresh fruit keeping quality and yield in Washington as a function of variety, type of fungicide(s) applied, and the number and timing of applications

Abstract: Replicated trials were conducted on cranberry beds with high levels of fruit rotting pathogens to assess fungicide effects on field rot, storage rot and yield. There was considerable variability between years, experiments and fungicide treatments. A few patterns emerged. Chlorothalonil applied early to mid-bloom consistently increased yield of marketable fruit (22 ± 9%) and reduced fruit rot (46 ± 8.6%). Similar patterns in fruit rot reduction were noted with combinations of azoxystrobin and prothioconazole and other combinations of groups 11 and 3 fungicides applied during bloom, but the effects on yield were less consistent. In multiple trials comparing the efficacy of single commercial fungicides applied during bloom, carboxamide + fluopyram, prothioconazole, and chlorothalonil all consistently increased yield and reduced fruit rot. Field and storage rot were assessed in decade-long variety trials in Oregon and Washington. Trials in Washington were fungicide-free. Crimson Queen, Scarlet Knight and BG’s had consistently higher field and storage rot than other new releases and standard comparisons. 2015 and 2016 packout data (% poor, 3 and 6 week keeping quality) from Washington’s fresh fruit growers was analyzed as a function of growers’ fungicide programs. Pre-bloom applications appear to have had little impact on fruit rot. Beds with 5-6 in-bloom fungicides had better quality fruit than beds with fewer fungicide applications. Prothioconazole was the most effective in-bloom fungicide. Post-bloom chlorothalonil applications improved fruit quality

Imágenes continuas de continuos hereditariamente indescomponibles

El teorema demostrado es que todo continuo métrico es imagen continua de algún continuo métrico hereditariamente indescomponible.The theorem proven here is that every compact metric continuum is a continuous image of some hereditarily indecomposable metric continuum

Effect of Nitrogen Fertilization on Cranberry Fresh Fruit Keeping Quality

Abstract: In this research project we compared the keeping quality of fruits harvested in plots fertilized during the last three years with 0, 13, 27, 40 and 54 lbs of nitrogen/acre. The nitrogen treatments were applied on small plots of 10 X 13 feet and split into four applications during bloom. The treatments were replicated two times per site in each of one organic and three conventional sites. The nitrogen fertilization had an effect on the keeping quality in both conventional and organic sites, with the best keeping quality obtained with a nitrogen fertilization of 0 or 13 lbs/acre (10% cumulative defects after 12 weeks). The worst keeping quality was obtained with a nitrogen fertilization of 54 lbs/acre (10% cumulative defects after 6 weeks). Most of the differences in keeping quality between treatments were related to fruit rot. As expected, the total percent weight of fruits smaller than 13/32 inches decreased and the number of white fruits increased as the amount of nitrogen fertilization increased. The highest average yield in the conventional sites was obtained in plots treated with 54 lbs of nitrogen/acre (43195 lbs/acre). It was closely followed by the plots treated with 27 and 40 lbs of nitrogen/acre (40 954 lbs/acre 35 876 lbs/acre respectively). Considering the keeping quality and the yield, the best nitrogen fertilization for fresh fruits in Quebec, based on this trial, seems to be between 27 and 40 lbs/acre, which confirms the standard recommendation in fresh fruit fertilization