Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor

Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions.Trabajo financiado por: Ministerio de Economía y Competitividad. Proyectos BFU2011-22678, SAF2014-51813-R (I+D+i) para Pedro María Fernández Salguero Ministerio de Economía y Competitividad, Instituto Carlos III, Red Temática de Investigación Cooperativa en Cáncer Junta de Extremadura. Ayudas GR10008, GR15008 CICE-FEDER-P09-CTS-4980, CICE-FEDERP12-CTS-2256, Plan Nacional de I+D+I 2008–2011 y 2013–2016 (FIS-FEDER-PI11/01489, FIS-FEDERPI14/02152), PCIN-2014-115-ERA-NET NEURON II, para José Luis García Pérez European Research Council ERC-Consolidator ERC-STG-2012-233764 International Early Career Scientist Beca de la Howard Hughes Medical Institute IECS-55007420 Programa Unión Europea de Fondos FEDERpeerReviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Machine Learning Strategies for Reconfigurable Intelligent Surface-Assisted Communication Systems—A Review

Machine learning (ML) algorithms have been widely used to improve the performance of telecommunications systems, including reconfigurable intelligent surface (RIS)-assisted wireless communication systems. The RIS can be considered a key part of the backbone of sixth-generation (6G) communication mainly due to its electromagnetic properties for controlling the propagation of the signals in the wireless channel. The ML-optimized (RIS)-assisted wireless communication systems can be an effective alternative to mitigate the degradation suffered by the signal in the wireless channel, providing significant advantages in the system’s performance. However, the variety of approaches, system configurations, and channel conditions make it difficult to determine the best technique or group of techniques for effectively implementing an optimal solution. This paper presents a comprehensive review of the reported frameworks in the literature that apply ML and RISs to improve the overall performance of the wireless communication system. This paper compares the ML strategies that can be used to address the RIS-assisted system design. The systems are classified according to the ML method, the databases used, the implementation complexity, and the reported performance gains. Finally, we shed light on the challenges and opportunities in designing and implementing future RIS-assisted wireless communication systems based on ML strategies

Beam tests and upgrades of MACACO II Compton telescope

Trabajo presentado en la XXXVII Reunión Bienal de la Real Sociedad Española de Física, celebrada en Zaragoza (España), del 15 al 20 de junio de 2019The use of hadron therapy in cancer treatment is increasing in the world given its precise energy deposition to the tumour and the dose reduction to healthy tissue as compared to conventional photon radiotherapy. Realtime treatment monitoring is one of the main challenges addressed nowadays. The IRIS group at IFIC-Valencia is developing a Compton telescope with this purpose. The system is made of three LaBr3 detector planes coupled to silicon photomultipliers (SiPMs). The first MACACO (Medical Applications CompAct COmpton camera) prototype demonstrated the viability of the proposed technology and served to identify its limitations. The second prototype features new detectors and image reconstruction codes, improving significantly the performance [1,2]. MACACO II has been characterized in the laboratory and in beam tests. It has been tested at CNA (Sevilla) with 18 MeV proton beams on a graphite target to produce 4.4 MeV gamma rays. Data have been taken with the system in different positions and beam intensities, and the target image has been reconstructed. Further tests have been carried out at KVI-CART (Groningen) with a 150 MeV proton beam impinging a PMMA target and the Bragg peak has been reconstructed in different positions. In spite of the significant progress, the system does not yet reach the necessary performance for the application and thus, possible improvements are being assessed. Tests include the evaluation of SiPMs of different types and manufacturers to enhance energy resolution and the improvement of the readout electronics. The MADDAQ board currently employed is being replaced by AliVATA, that will allow to operate the three system detectors with just one board and improve the readout speed. In addition, tests are being carried out with the PETsys system, improving significantly the detector timing resolution

Laboratory and test-beam results with MACACO II

Trabajo presentado en el IEEE Nuclear Science Symposium and Medical Imaging Conference, celebrada en Manchester, del 26 de octubre al 2 de noviembre de 2019The IRIS group at IFIC Valencia is developing a three-layer Compton camera for treatment monitoring in ion beam therapy. The system is composed of three detector planes, each made of a LaBr 3 monolithic crystal coupled to SiPM arrays. The first prototype (MACACO), was fully characterised in the laboratory and in beam tests demonstrating the feasibility of the proposed technology. A second prototype (MACACO II), described in this work, is currently being developed to improve performance. The SiPM arrays have been replaced by newer models, leading to an improved detector energy resolution which translates into a higher spatial resolution of the telescope. In addition, the image reconstruction code has been improved with an accurate model of the sensitivity matrix. Furthermore, a new spectral reconstruction algorithm for Compton cameras with two planes has been developed showing promising results. The system has been fully characterised in the laboratory at controlled temperature and also tested in two accelerator facilities. The first involved a proton beam of 18 MeV impinging a graphite target. The results allowed the successful reconstruction of two target positions separated by 5 mm. The second test beam used protons of 150 MeV impinging on a PMMA target. The results show that for measurements taken in different positions of the PMMA target the reconstructed Bragg peak position is related to the PMMA position

Memorias IX Congreso Geológico Venezolano (3)

Memorias IX Congreso Geológico Venezolano (3