SETDB1 is a histone H3K9 methyltransferase that has a critical role in early development. It is located within a melanoma susceptibility locus and facilitates melanoma formation. However, the mechanism by which SETDB1 regulates tumorigenesis remains unknown. Here we report the molecular interplay between SETDB1 and the well-known hotspot gain-of-function (GOF) TP53 R249S mutation. We show that in hepatocellular carcinoma (HCC) SETDB1 is overexpressed with moderate copy number gain, and GOF TP53 mutations including R249S associate with this overexpression. Inactivation of SETDB1 in HCC cell lines bearing the R249S mutation suppresses cell growth. The TP53 mutation status renders cancer cells dependent on SETDB1. Moreover, SETDB1 forms a complex with p53 and catalyses p53K370 di-methylation. SETDB1 attenuation reduces the p53K370me2 level, which subsequently leads to increased recognition and degradation of p53 by MDM2. Together, we provide both genetic and biochemical evidence for a mechanism by which SETDB1 regulates cancer cell growth via methylation of p53.

The present study aimed to determine the characteristics of patients with dermatomyositis (DM) in order to identify predictors of cancer in these patients. Data of 239 patients with DM, treated at Yuhuangding Hospital between 1997 and 2016, was retrospectively assessed. The patients' demographic, clinical, survival and laboratory data were analyzed. Of the 239 patients, 43 developed malignancies. In 30 (69.77%) patients, the malignancy was detected within 1 year before or after DM diagnosis. There were 15 (34.88%) fatalities. Lung cancer was the most common type of malignancy identified (n=6, 13.95%), and adenocarcinoma was the most common pathological type (n=6, 13.95%). Older age, absence of interstitial lung disease, and absence of arthralgia were demonstrated to be independent risk factors for malignancy. Myositis-specific autoantibody expression, specifically anti-TIF1γ positivity and/or anti-MDA5 negativity, was associated with cancer in patients with DM. The survival rate was significantly lower in patients with malignancy than in patients without malignancy. Patients with DM had a high incidence of malignancy and a poor prognosis. Lung cancer and adenocarcinoma are common among patients with DM in northern China. Cancer screening should be conducted in all DM patients, particularly within 1 year of DM diagnosis. Older age is a risk factor for malignancy in DM patients, while interstitial lung disease and arthralgia are protective factors. Myositis-specific autoantibody detection may be useful for cancer screening in patients with DM.

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Programming robots for general purpose applications is extremely challenging due to the great diversity of end-user tasks ranging from manufacturing environments to personal homes. Recent work has focused on enabling endusers to program robots using Programming by Demonstration. However, teaching robots new actions from scratch that can be reused for unseen tasks remains a difficult challenge and is generally left up to robotic experts. We propose iRoPro, an interactive Robot Programming framework that allows endusers to teach robots new actions from scratch and reuse them with a task planner. In this work we provide a system implementation on a two-armed Baxter robot that (i) allows simultaneous teaching of low-and high-level actions by demonstration, (ii) includes a user interface for action creation with condition inference and modification, and (iii) allows creating and solving previously unseen problems using a task planner for the robot to execute in real-time. We evaluate the generalisation power of the system on six benchmark tasks and show how taught actions can be easily reused for complex tasks. We further demonstrate its usability with a user study (N=21), where users completed eight tasks to teach the robot new actions that are reused with a task planner. The study demonstrates that users with any programming level and educational background can easily learn and use the system.