11 research outputs found
Nitrogen related diffuse pollution from horticulture production - mitigation practices and assessment strategies
ReviewAgriculture is considered one of the main nitrogen (N) pollution sources through the diffuse
emissions of ammonia (NH3) and nitrous oxide (N2O) to the atmosphere and nitrate (NO3
) to water
bodies. The risk is particularly high in horticultural production systems (HPS), where the use of water
and fertilizers is intensive and concentrated in space and time, and more specifically, in the case of
vegetable crops that have high growth rates, demanding an abundant supply of water and nitrogen
forms. Therefore, to comply with the EU environmental policies aimed at reducing diffuse pollution
in agriculture, there is the need for mitigation practices or strategies acting at different levels such as
the source, the timing and the transport of N. HPS are often well suited for improvement practices,
but efficient and specific tools capable of describing and quantifying N losses for these particular
production systems are required. The most common mitigation strategies found in the literature
relate to crop, irrigation and fertilization management. Nevertheless, only the success of a mitigation
strategy under specific conditions will allow its implementation to be increasingly targeted and more
cost effective. Assessment methods are therefore required to evaluate and to quantify the impact of
mitigation strategies in HPS and to select the most promising onesinfo:eu-repo/semantics/publishedVersio
Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas
The broad clinical spectrum of neuroblastoma ranges from spontaneous regression to rapid progression despite intensive multimodal therapy. This diversity is not fully explained by known genetic aberrations, suggesting the possibility of epigenetic involvement in pathogenesis. In pursuit of this hypothesis, we took an integrative approach to analyze the methylomes, transcriptomes, and copy number variations in 105 cases of neuroblastoma, complemented by primary tumor-and cell line-derived global histone modification analyses and epigenetic drug treatment in vitro. We found that DNA methylation patterns identify divergent patient subgroups with respect to survival and clinicobiologic variables, including amplified MYCN. Transcriptome integration and histone modification-based definition of enhancer elements revealed intragenic enhancer methylation as a mechanism for high-risk-associated transcriptional deregulation. Furthermore, in high-risk neuroblastomas, we obtained evidence for cooperation between PRC2 activity and DNA methylation in blocking tumor-suppressive differentiation programs. Notably, these programs could be re-activated by combination treatments, which targeted both PRC2 and DNA methylation. Overall, our results illuminate how epigenetic deregulation contributes to neuroblastoma pathogenesis, with novel implications for its diagnosis and therapy. (C) 2016 AACR
ALK positively regulates MYCN activity through repression of HBP1 expression
ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis. To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential. We show that mutant ALK downregulates the ‘HMG-box transcription factor 1’ (HBP1) through the PI3K-AKT–FOXO3a signaling axis. HBP1 inhibits both the transcriptional activating and repressing activity of MYCN, the latter being mediated through PRC2 activity. HBP1 itself is under negative control of MYCN through miR-17~92. Combined targeting of HBP1 by PI3K antagonists and MYCN signaling by BET- or HDAC-inhibitors blocks MYCN activity and significantly reduces tumor growth, suggesting a novel targeted therapy option for high-risk neuroblastoma