Hypoxia in the Initiation and Progression of Neuroblastoma Tumours

Neuroblastoma is the most frequent extracranial solid tumour in children, causing 10% of all paediatric oncology deaths. It arises in the embryonic neural crest due to an uncontrolled behaviour of sympathetic nervous system progenitors, giving rise to heterogeneous tumours. Low local or systemic tissue oxygen concentration has emerged as a cellular stimulus with important consequences for tumour initiation, evolution and progression. In neuroblastoma, several evidences point towards a role of hypoxia in tumour initiation during development, tumour cell differentiation, survival and metastatic spreading. However, the heterogeneous nature of the disease, its developmental origin and the lack of suitable experimental models have complicated a clear understanding of the effect of hypoxia in neuroblastoma tumour progression and the molecular mechanisms implicated. In this review, we have compiled available evidences to try to shed light onto this important field. In particular, we explore the effect of hypoxia in neuroblastoma cell transformation and differentiation. We also discuss the experimental models available and the emerging alternatives to study this problem, and we present hypoxia-related therapeutic avenues being explored in the field.Spanish Ministry of Science and Innovation SAF program (grant number SAF2016-80412-P

Consultorio contable y tributario de la Universidad Libre Seccional Pereira

CD-T 343.04 A18;168 p.Se analiza la factibilidad financiera y social de la creación de un consultorio contable y tributario en la Universidd Libre Seccional Pereira, adscrito al programa de contaduría pública, para prestar asesoría y consultoría a personas naturales, mypimes y la gran empresa de Pereira y Dosquebradas, a título gratuito y oneroso.Universidad Libre Seccional Pereir

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans : joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Hypoxia in the Initiation and Progression of Neuroblastoma Tumours

Neuroblastoma is the most frequent extracranial solid tumour in children, causing 10% of all paediatric oncology deaths. It arises in the embryonic neural crest due to an uncontrolled behaviour of sympathetic nervous system progenitors, giving rise to heterogeneous tumours. Low local or systemic tissue oxygen concentration has emerged as a cellular stimulus with important consequences for tumour initiation, evolution and progression. In neuroblastoma, several evidences point towards a role of hypoxia in tumour initiation during development, tumour cell differentiation, survival and metastatic spreading. However, the heterogeneous nature of the disease, its developmental origin and the lack of suitable experimental models have complicated a clear understanding of the effect of hypoxia in neuroblastoma tumour progression and the molecular mechanisms implicated. In this review, we have compiled available evidences to try to shed light onto this important field. In particular, we explore the effect of hypoxia in neuroblastoma cell transformation and differentiation. We also discuss the experimental models available and the emerging alternatives to study this problem, and we present hypoxia-related therapeutic avenues being explored in the field.This research was funded by the Spanish Ministry of Science and Innovation SAF program (grant number SAF2016-80412-P) co-funded by FEDER funds. MAG is supported by a fellowship from the “Asociación Niños Enfermos de Neuroblastoma (NEN).Ye

Hypoxia in the Initiation and Progression of Neuroblastoma Tumours

This article belongs to the Special Issue Neuroblastoma Molecular Biology and Therapeutics.Neuroblastoma is the most frequent extracranial solid tumour in children, causing 10% of all paediatric oncology deaths. It arises in the embryonic neural crest due to an uncontrolled behaviour of sympathetic nervous system progenitors, giving rise to heterogeneous tumours. Low local or systemic tissue oxygen concentration has emerged as a cellular stimulus with important consequences for tumour initiation, evolution and progression. In neuroblastoma, several evidences point towards a role of hypoxia in tumour initiation during development, tumour cell differentiation, survival and metastatic spreading. However, the heterogeneous nature of the disease, its developmental origin and the lack of suitable experimental models have complicated a clear understanding of the effect of hypoxia in neuroblastoma tumour progression and the molecular mechanisms implicated. In this review, we have compiled available evidences to try to shed light onto this important field. In particular, we explore the effect of hypoxia in neuroblastoma cell transformation and differentiation. We also discuss the experimental models available and the emerging alternatives to study this problem, and we present hypoxia-related therapeutic avenues being explored in the field.This research was funded by the Spanish Ministry of Science and Innovation SAF program (grant number SAF2016-80412-P) co-funded by FEDER funds. MAG is supported by a fellowship from the “Asociación Niños Enfermos de Neuroblastoma (NEN)

Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination

Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It’s well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death. The two major pathways for repair of DSB are non-homologous end joining (NHEJ) and homologous recombination (HR). Recently, multiple functions for the HR machinery have been identified at arrested forks. Here we investigate in more detail the importance of the lesions induced by zebularine in terms of DNA damage and cytotoxicity as well as the role of HR in the repair of these lesions. When we examined the contribution of NHEJ and HR in the repair of DSB induced by zebularine we found that these breaks were preferentially repaired by HR. Also we show that the production of DSB is dependent on active replication. To test this, we determined chromosome damage by zebularine while transiently inhibiting DNA synthesis. Here we report that cells deficient in single-strand break (SSB) repair are hypersensitive to zebularine. We have observed more DSB induced by zebularine in XRCC1 deficient cells, likely to be the result of conversion of SSB into toxic DSB when encountered by a replication fork. Furthermore we demonstrate that HR is required for the repair of these breaks. Overall, our data suggest that zebularine induces replication-dependent DSB which are preferentially repaired by HR

Analysing natural ventilation to reduce the cooling energy consumption and the fuel poverty of social dwellings in coastal zones

In southern European countries, summer temperatures could contribute to a high cooling energy consumption. Family units with fewer economic resources living in social dwellings could suffer from fuel poverty if they want to use air conditioning systems. Otherwise, they could face discomfort hours because of a natural ventilation without clear control criteria. This study analyses quantitatively and qualitatively the possibilities of natural ventilation through mixed-mode and the possibility of reducing fuel poverty for family units living in social dwellings. For this purpose, the application of a natural ventilation approach was analysed through an adaptive behaviour based on EN 16798-1: 2019. A case study of 51 social dwellings was analysed by using various operation hypothesis between 2015 and 2019. The results showed the potential of using mixed-mode approaches based on the categories from EN 16798-1:2019 to achieve savings in the energy consumption and to remove cases of fuel poverty in low-income families. Likewise, surveys in which families living in these cities participated reflected the great awareness of the natural ventilation use, although there is not a clear criterion of the need of this ventilation for thermal comfort, as well as the need of a supportive use of air conditioning systems. Finally, the similarity of the climate conditions of the city analysed and the coastal cities from various countries in the south of Europe shows the possibility of using ventilation strategies as energy saving measures in other regions. © 2020 Elsevier Lt

Espirales de reflexividad crítica y propositiva para escribir la educación media de Bogotá

399 p. Libro digita