Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: Functional and therapeutic implications

This article is made available through the Brunel Open Access Publishing Fund. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear. Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non-canonical E box sequence CACGCG in the 5′-flanking region. Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members. MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU. Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects. The expression of CLU can be restored in MYCN-amplified cells by epigenetic drugs with therapeutic results. Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference. Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU.SPARKS, The Neuroblastoma Society, a Wellcome Trust grant (to A. S.), and the Italian Association for Cancer Research

Hydrologic Niches Explain Species Coexistence and Abundance in a Shrub-Steppe System

Differences in vertical root distributions are often assumed to create resource uptake tradeoffs that determine plant growth and coexistence. Yet, most plant roots are in shallow soils, and data linking root distributions with resource uptake and plant abundances remain elusive. Here we used a tracer experiment to describe the vertical distribution of absorptive roots of dominant species in a shrub‐steppe ecosystem. To describe how these different rooting distributions affected water uptake in wet and dry soils across a growing season, we used a soil water movement model. Root traits were then correlated with plant landscape abundances. Deeper root distributions extracted more soil water, had larger unique hydrological niches and were more abundant on the landscape. Though most (\u3e 50%) root biomass and tracer uptake occurred in shallow soils (0–32 cm), the depth of 50% of tracer uptake varied from 11 to 32 cm across species and species with deeper rooting distributions were more abundant on the landscape (R2 = 0.95). The water flow model revealed that deeper rooting distributions should extract more soil water (i.e., a range of 60 to 113 mm of soil water) because shallow roots were often in dry soils. These potential water uptake values were tightly correlated with species’ abundances on the landscape (R2 = 0.90). Finally, each species’ rooting distribution demonstrated a depth and time at which it could extract more soil water than any other rooting distribution, and the size of these unique hydrological niches indices was also well correlated with species’ abundances (R2 = 0.89). Synthesis. Our results demonstrate not only a correlation between root distributions and species abundance, but also the mechanism through which differences in rooting distributions can determine resource uptake and niche partitioning, even when most roots are found in shallow soils

Primary production of the central grassland region of the United States

Includes bibliographical references (pages 44-45).Aboveground net primary production of grasslands is strongly influenced by the amount and distribution of annual precipitation. Analysis of data collected at 9500 sites throughout the central United States confirmed the overwhelming importance of water availability as a control of production. The regional spatial pattern of production reflected the east-west gradient in annual precipitation. Lowest values of aboveground net primary production were observed in the west and highest values in the east. This spatial pattern was shifted eastward during unfavorable years and westward during favorable years. Variability in production among years was maximum in northern New Mexico and southwestern Kansas and decreased towards the north and south. The regional pattern of production was largely accounted for by annual precipitation. Production at the site level was explained by annual precipitation, soil water-holding capacity, and an interaction term. Our results support the inverse texture hypothesis. When precipitation is 370 mm/yr

Stressed caregivers. An observational study in a rehabilitation care home in western Sicily

Introduction: Caregiver is the person who takes care of the patient from the practical point of view, helping him in managing the disease and carrying out daily activities, but also supporting him on an emotional level. Caregiver burnout is a state of physical, emotional, and mental exhaustion that may be accompanied by a change in attitude from positive and caring to negative and unconcerned. The aim of the study was to understand what factors were associated with having panic attacks or crying crises in the caregivers of our study population. Materials and methods: The study design is observational. An anonymous questionnaire was administered to caregivers of the patients of a hospital for the intensive post-acute rehabilitation from April 2016 to December 2018. The statistical significance level chosen for the entire analysis was 0.05. The covariates to be included were selected using a stepwise backward selection process, with a univariate p-value <0.25 as the main criterion. Results are expressed as adjusted Odds Ratio (aOR) with 95% Confidence Intervals (CI). Results: The sample consists of 302 caregivers (60.93% was females and 39.07% was males). The mean age of the sample is 53.42 years old (SD ± 12.19). The multivariable logistic regression model shows that the risk to have panic or crying crisis is significantly associated with the following indipendent variables: female gender (aOR 27.06); living with the patient (aOR 4.38); had claimed that the problems related to the illness of their family member is a source of stress (aOR 23.54), smoking cigarettes (aOR 14.68); had claimed that taking care of their client affected their personal financial statement/career (aOR 5.95), having free time (aOR 7.68). Conclusions: In our study we found a greater probability of having panic attacks or crying crises in female subjects, smokers, who think they have sacrificed their careers to take care of the person they follow from a welfare point of view. Certainly in the light of what has emerged it is necessary to dedicate and pay close attention to the psychological and social aspects of the caregiver

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Comparative performance of MRI-derived PRECISE scores and delta-radiomics models for the prediction of prostate cancer progression in patients on active surveillance

Objectives: To compare the performance of the PRECISE scoring system against several MRI-derived delta-radiomics models for predicting histopathological prostate cancer (PCa) progression in patients on active surveillance (AS). // Methods: The study included AS patients with biopsy-proven PCa with a minimum follow-up of 2 years and at least one repeat targeted biopsy. Histopathological progression was defined as grade group progression from diagnostic biopsy. The control group included patients with both radiologically and histopathologically stable disease. PRECISE scores were applied prospectively by four uro-radiologists with 5–16 years’ experience. T2WI- and ADC-derived delta-radiomics features were computed using baseline and latest available MRI scans, with the predictive modelling performed using the parenclitic networks (PN), least absolute shrinkage and selection operator (LASSO) logistic regression, and random forests (RF) algorithms. Standard measures of discrimination and areas under the ROC curve (AUCs) were calculated, with AUCs compared using DeLong’s test. // Results: The study included 64 patients (27 progressors and 37 non-progressors) with a median follow-up of 46 months. PRECISE scores had the highest specificity (94.7%) and positive predictive value (90.9%), whilst RF had the highest sensitivity (92.6%) and negative predictive value (92.6%) for predicting disease progression. The AUC for PRECISE (84.4%) was non-significantly higher than AUCs of 81.5%, 78.0%, and 80.9% for PN, LASSO regression, and RF, respectively (p = 0.64, 0.43, and 0.57, respectively). No significant differences were observed between AUCs of the three delta-radiomics models (p-value range 0.34–0.77). // Conclusions: PRECISE and delta-radiomics models achieved comparably good performance for predicting PCa progression in AS patients

Who Believes in the Giant Skeleton Myth? An Examination of Individual Difference Correlates

This study examined individual difference correlates of belief in a narrative about the discovery of giant skeletal remains that contravenes mainstream scientific explanations. A total of 364 participants from Central Europe completed a survey that asked them to rate their agreement with a short excerpt describing the giant skeleton myth. Participants also completed measures of the Big Five personality factors, New Age orientation, anti-scientific attitudes, superstitious beliefs, and religiosity. Results showed that women, as compared with men, and respondents with lower educational qualifications were significantly more likely to believe in the giant skeleton myth, although effect sizes were small. Correlational analysis showed that stronger belief in the giant skeleton myth was significantly associated with greater anti-scientific attitudes, stronger New Age orientation, greater religiosity, stronger superstitious beliefs, lower Openness to Experience scores, and higher Neuroticism scores. However, a multiple regression showed that the only significant predictors of belief in myth were Openness, New Age orientation, and anti-scientific attitudes. These results are discussed in relation to the potential negative consequences of belief in myths

Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer.

International audienc

Action scales for quantum decoherence and their relation to structures in phase space

A characteristic action $\Delta S$ is defined whose magnitude determines some properties of the expectation value of a general quantum displacement operator. These properties are related to the capability of a given environmental `monitoring' system to induce decoherence in quantum systems coupled to it. We show that the scale for effective decoherence is given by $\Delta S\approx\hbar$. We relate this characteristic action with a complementary quantity, $\Delta Z$, and analyse their connection with the main features of the pattern of structures developed by the environmental state in different phase space representations. The relevance of the $\Delta S$-action scale is illustrated using both a model quantum system solved numerically and a set of model quantum systems for which analytical expressions for the time-averaged expectation value of the displacement operator are obtained explicitly.Comment: 12 pages, 3 figure

Vegetation dynamics within afforested coastal areas: regeneration by native species or invasion by alien species?

During the last century, massive reforestation projects along the dunes of the southern Sicily have been carried out. Such interventions, far from being in line with the current trends of close-to-nature silviculture, are, however, particularly interesting to assess the vegetation dynamics in afforestation areas. Furthermore, these kind of interventions may determine two opposite effects, that is renaturalization by native woody species or invasion by alien species. Acacia spp. are among the most widespread and prominent invaders within Mediterranean-climate areas, where they have already shown the capability to deeply change the characters and the functioning of native ecosystems. For instance, Acacia longifolia (Andrews) Willd. may successfully invade the understory of pine forests, causing the alteration of the water balance and carbon storage of the whole forest ecosystem. In Sicily, especially in the last decades, Acacia saligna started to abundantly regenerate in many natural and semi-natural areas, with a stark preference for dune and coastal afforested sites. The nature reserve \u201cFoce del Fiume Platani\u201d represents an excellent case study in this respect