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DNA methyl transferase-1 or DNMT1 maintains DNA methylation in the genome and is important for regulating gene expression in cells. Aberrant changes in DNMT1 activity and DNA methylation are commonly observed in cancers and many other diseases. Recently, a number of long intergenic non-protein-coding RNAs or lincRNAs have been shown to play a role in regulating DNMT1 activity. CCDC26 is a nuclear lincRNA that is frequently mutated in cancers and is a hotbed for disease-associated single nucleotide changes. However, the functional mechanism of CCDC26 is not understood. Here, we show that this lincRNA is concentrated on the nuclear periphery. Strikingly, in the absence of CCDC26 lincRNA, DNMT1 is mis-located in the cytoplasm, and the genomic DNA is significantly hypomethylated. This is accompanied by double-stranded DNA breaks and increased cell death. These results point to a previously unrecognized mechanism of lincRNA-mediated subcellular localization of DNMT1 and regulation of DNA methylation.With the advent of deep generative models in computational chemistry, in-silico drug design is undergoing an unprecedented transformation. Although deep learning approaches have shown potential in generating compounds with desired chemical properties, they disregard the cellular environment of target diseases. Bridging systems biology and drug design, we present a reinforcement learning method for de novo molecular design from gene expression profiles. We construct a hybrid Variational Autoencoder that tailors molecules to target-specific transcriptomic profiles, using an anticancer drug sensitivity prediction model (PaccMann) as reward function. Without incorporating information about anticancer drugs, the molecule generation is biased toward compounds with high predicted efficacy against cell lines or cancer types. https://www.selleckchem.com/products/Temsirolimus.html The generation can be further refined by subsidiary constraints such as toxicity. Our cancer-type-specific candidate drugs are similar to cancer drugs in drug-likeness, synthesizability, and solubility and frequently exhibit the highest structural similarity to compounds with known efficacy against these cancer types.Breakthroughs in gene editing technologies have made it feasible to create genetically altered (GA) non-human primate (NHP) models of disease. This area of research is accelerating, particularly in China, Japan and the USA, and could lead to an increase in NHP use globally. The hope is that genetic models in animal species closely related to humans will significantly improve understanding of neurological diseases and validation of potential therapeutic interventions, for which there is a dire need. However, the creation and use of GA NHPS raises serious animal welfare and ethical issues, which are highlighted here. It represents a step change in how these highly sentient animals are used in biomedical research, because of the large numbers required, inherent wastage and the sum of the harms caused to the animals involved. There is little evidence of these important issues being addressed alongside the rapidly advancing science. We are still learning about how gene editing tools work in NHPS, and significant added scientific and medical benefit from GA NHP models has yet to be demonstrated. Together, this suggests that current regulatory and review frameworks, in some jurisdictions at least, are not adequately equipped to deal with this emerging, complex area of NHP use.Genetic screens provide a mechanism to identify genes involved with different cellular and organismal processes. Using a Flp/FRT screen in the Drosophila eye we identified mutations that result in alterations and de-regulation of cell growth and division. From this screen a group of undergraduate researchers part of the Fly-CURE consortium mapped and characterized a new allele of the gene Hippo, HpoN.1.2.Some case reports described nephrotic syndrome (NS) associated with administering various vaccines in two last decades. They report only 1 year follow-up. We want to summarize the 17-year clinical follow-up of the patient who had been reported in 2000 because of developing NS after hepatitis B vaccination. Our patient first suffered from NS following hepatitis B vaccination in 4 years old. He had been treated with standard prednisolone regimen resulting in complete remission. After the first diagnosis, he had three relapses in following years. Each relapse developed after Salk, pneumococcal, and flu vaccines, respectively. Relapses had been easily controlled by prednisolone. He had seven relapses until 14 years of age. Fortunately, no relapse has been observed between 2009 and 2016. Although he has been taking alendronate and Vitamin-D for osteoporosis, he is a healthy young adult now. We think that some vaccines may induce relapses in NS, as a triggering factor without being the primarily responsible factors.Congenital absence of the pericardium is not a common condition in daily practice. There are no obvious and clear symptoms. This condition, which is diagnosed incidentally, may cause some complications when not diagnosed. Therefore, imaging techniques, such as echocardiography, are essential. In this article, we present a rare case of pericardial agenesis.Gemella morbillorum is one of the rare causative microorganisms of endocarditis. We herein report a case of infective endocarditis in a patient with bicuspid aortic valve caused by G. morbillorum. Infective endocarditis diagnosis was established based on the Modified Duke's criteria. The patient was successfully treated with medical-surgical management.SARS-CoV-2 is still a major threat to the world. In this pandemic, transplantation activities have largely been affected worldwide. We are still facing with this pandemic; however, after regulations, we have started our transplantation activities. We report the first kidney transplantation whose recipient and living donor recovered from COVID-19. A 31-year-old male with renal failure was admitted for transplantation with an ABO-compatible relative. The recipient and the donor were tested for COVID-19 before transplantation, and they were both positive with a polymerase chain reaction. The recipient had minor symptoms and received therapy; the living donor also received therapy. Thirty days after recovery, surgery was performed successfully. The recipient was discharged with mycophenolate mofetil (MMF), tacrolimus, and steroid 15 days after surgery. In the follow-up, they were both negative for COVID-19 45 days after surgery. Although there is missing literature regarding safety concerns and short-term follow-up, living-donor transplantation may be considered for patients, who recovered from COVID-19, after careful selection with paying attention to precautions.
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