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Notably, overexpressing TPO in EGF-stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Cancer cells can activate the alternative lengthening of telomeres (ALT) pathway to promote replicative immortality. The ALT pathway promotes telomere elongation through a homologous recombination pathway known as break-induced replication (BIR), which is often engaged to repair single-ended double-stranded breaks (DSBs). Single-ended DSBs are resected to promote strand invasion and facilitate the formation of a local displacement loop (D-loop), which can trigger DNA synthesis, and ultimately promote telomere elongation. However, the exact proteins involved in the maturation, migration, and resolution of D-loops at ALT telomeres are unclear. In vitro, the DNA translocase RAD54 both binds D-loops and promotes branch migration suggesting that RAD54 may function to promote ALT activity. Here, we demonstrate that RAD54 is enriched at ALT telomeres and promotes telomeric DNA synthesis through its ATPase-dependent branch migration activity. Loss of RAD54 leads to the formation of unresolved recombination intermediates at telomeres that form ultra-fine anaphase bridges in mitosis. These data demonstrate an important role for RAD54 in promoting ALT-mediated telomere synthesis. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.We read the recent article -"Obesity, transplantation and bariatric surgery An evolving solution for growing epidemic"(1) with great interest. The authors have provided excellent evidence in favor of bariatric surgery in the transplant population. We agree in principle that bariatric surgery improves post-transplant outcomes based on the available evidence. This article is protected by copyright. All rights reserved.PURPOSE To investigate the impact of breath-hold reproducibility on liver motion using a respiratory motion management device. METHODS Forty-four patients with hepatic tumors, treated with SBRT with breath-hold, were randomly selected for this study. All patients underwent three consecutive computed tomography (CT) scans using active breath-hold coordinator (ABC) with three repeated single breath-hold during simulation. The three CT scans were labeled as ABC1-CT, ABC2-CT, and ABC3-CT. https://www.selleckchem.com/products/arry-382.html Displacements of centroids of the entire livers among the three ABC-CTs were measured as a surrogate for intrafractional motion. For each patient, two different treatment plans were prepared (a) a clinical plan using a 5-mm expansion of an ITV that encompassed all three GTVs from each of the three ABC-CTs, and (b) a research plan using a 5-mm expansion of the GTV from only ABC1-CT to create PTV. The clinical plan acceptance criteria were that 95% of the PTV and 99% of the GTV received 100% of the prescription dose. Dosimetric encine.PURPOSE Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) is a population based database administered by the AEMPS (Spanish Agency for Medicines) of longitudinal electronic medical records (EMR) of patients attended in primary care. Its main purpose is to serve as source of information for independent studies on drug safety and support of medicines regulation activities. This article aim is to describe the characteristics of BIFAP, how to access the database and a summary of its potential for research. METHODS Health problems are registered by primary care physicians as episodes of care and include socio-demographic data, results of diagnostic procedures, lifestyle data, general data, and interventions. A proportion of data on hospitalizations and specialist care are currently available through linkage with other data sources. EMRs of the Spanish healthcare system are provided by the regional administrations. Specific data extraction and standardization processes are performed. RESULTS BIFAP includes data from 12 million patients starting in 2001 and updated annually. Validation of drug and diagnosis definitions has been ascertained. Participation in international collaborative projects and a number of articles in peer reviewed journals reflect its contribution to the knowledge of the risks associated with medicines and drug utilization patterns. CONCLUSIONS BIFAP is a useful tool for generating scientific evidence on medicines related issues, helping regulatory decision making in Europe. The main strengths of BIFAP are related to large sample size, population-based, longitudinal nature and annual update of data. BIFAP shares common challenges with similar data sources including accurate and efficient identification of health outcomes and of treatment exposure. © 2020 John Wiley & Sons Ltd.HLA-DRB1*15170 differs from HLA-DRB1*15010103 by one nucleotide substitution at codon 85 in exon 2. This article is protected by copyright. All rights reserved.Guanine-quadruplexes (G4) included in RNA molecules exert several functions in controlling gene expression at post-transcriptional level; however, the molecular mechanisms of G4-mediated regulation are still poorly understood. Here, we describe a regulatory circuitry operating in the early phases of murine muscle differentiation in which a long non-coding RNA (SMaRT) base pairs with a G4-containing mRNA (Mlx-γ) and represses its translation by counteracting the activity of the DHX36 RNA helicase. The time-restricted, specific effect of lnc-SMaRT on the translation of Mlx-γ isoform modulates the general subcellular localization of total MLX proteins, impacting on their transcriptional output and promoting proper myogenesis and mature myotube formation. Therefore, the circuitry made of lnc-SMaRT, Mlx-γ, and DHX36 not only plays an important role in the control of myogenesis but also unravels a molecular mechanism where G4 structures and G4 unwinding activities are regulated in living cells. © 2020 The Authors. Published under the terms of the CC BY 4.
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