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This article is protected by copyright. All rights reserved.BACKGROUND The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States. METHODS Data on new cancer diagnoses during 2001 through 2016 were obtained from the Centers for Disease Control and Prevention-funded and National Cancer Institute-funded population-based cancer registry programs and compiled by the North American Association of Central Cancer Registries. Data on cancer deaths during 2001 through 2017 were obtained from the National Center for Health Statistics’ National Vital Statistics System. Trends in incidence and death rates for all cancers combined and for the leading cancer types by sex, racial/ethnic group, and age were estimated by joinpoint analysis and characterized by the average annual percent change during the most recent 5 years (2012-2016 for incidence and 2013-2017 for mortality). RESULTreflect population changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are found early. Population-based cancer incidence and mortality data can be used to inform efforts to decrease the cancer burden in the United States and regularly monitor progress toward goals. © 2020 American Cancer Society.Due to the increased usage of high throughput sequencing for the diagnosis of genetically inherited disorders, it is vital to evaluate the risk of new variants and novel genes before accepting them in clinical practice. However, discordant in silico and in vitro results, challenge estimations of the effect of an identified genetic variant. We aimed to comprehensively evaluate pathogenic and polymorphic variants using the activation-induced-cytidine-deaminase (AICDA) gene as a model. We systematically searched and identified patients with confirmed AICDA-mutations. Population-based-databases were screened for germline-polymorphic-AICDA-variants. Activity of AICDA-mutant and severity of the clinical and immunologic-phenotype were showed comparing 108 population-based-variants with 48 pathogenic mutations (12 overlapping-variants). Discordant predictions of different algorithms were observed on average in 38% of the population-database variants, mainly for missense mutations. Functional activity in mutations observed only in patients was significantly lower than variants in the population databases and overlapping-variants between patients and the general-population. Surprisingly, overlapping-variants had an even higher functional activity than the most common polymorphic-variants; however, their pathogenicity was still distinguishable when their function was compared with wild-type AICDA. Classifications of genetic variants cannot readily be translated into a clinical implication. Combined databases of functional and computational assays should therefore be developed for each specific gene. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Nik-related kinase (Nrk) is a member of the germinal center kinase IV family and suppresses Akt signaling. In vivo, Nrk prevents placental hyperplasia and breast cancer formation. Here, we show that Nrk is regulated by the chaperone-dependent ubiquitin ligase carboxyl terminus of Hsp70-interacting protein (CHIP). Immunoprecipitation and LC-MS/MS analysis reveal that Nrk preferentially interacts with CHIP and Hsp70/90 family proteins. Nrk protein levels are decreased by CHIP overexpression and increased by siRNA-mediated CHIP knockdown. Our results indicate that Nrk is ubiquitinated by CHIP in a chaperone-dependent manner, resulting in its proteasomal degradation. CHIP targets a fraction of Nrk molecules that have lost the ability to regulate Akt signaling. We conclude that CHIP plays an important role in regulating Nrk protein levels. This article is protected by copyright. All rights reserved.Myeloid differentiation factor 88 (Myd88) plays an important role in both innate and adaptive immune response. In this study, the full-length complementary DNA (cDNA) of myd88 from Misgurnus anguillicaudatus was characterized. The myd88 cDNA is 1333 bp in length and contains an 855 bp open reading frame encoding a predicted protein of 284 amino acids. The predicted protein possesses typical Myd88 domain structural features including a death domain in the N-terminus, and box 1, 2, and 3 motifs of the Toll/IL-1 receptor domain in the C-terminus. selleck compound Quantitative real-time PCR (qRT-PCR) revealed that myd88 messenger RNA (mRNA) was ubiquitously expressed in all examined tissues, especially highly in brain, kidney, blood, intestines and liver. qRT-PCR and western blotting were used to determine the mRNA and protein levels of Myd88 after Aeromonas veronii challenge, respectively. The Myd88 was remarkably upregulated in response to infection of A. veronii. These results suggested that Myd88 may play a vital role during the immune response of M. anguillicaudatus against bacterial infection. © 2020 The Fisheries Society of the British Isles.PURPOSE To model 4-Dimensional (4D) Relative Biological Effectiveness (RBE)-weighted dose variations in abdominal lesions treated with scanned carbon ion beam in case of irregular breathing motion. METHODS The proposed method, referred to as bioWED method, combines the simulation of tumor motion in a patient- and beam-specific water equivalent depth (WED)-space with RBE modeling, aiming at the estimation of RBE-weighted dose changes due to respiratory motion. The method was validated on a phantom, simulating gated and free breathing dose delivery, and on a patient case, for which free breathing irradiation was assumed and both amplitude and baseline breathing irregularities were simulated through a respiratory motion model. We quantified (i) the effect of motion on the equivalent uniform dose (EUD) and the RBE-weighted dose-volume histograms (DVH), by comparing the planned dose distribution with “ground truth” 4D RBE-weighted doses computed using 4DCT data, and (ii) the estimation error, by comparing the doses estimated with the bioWED method to “ground truth” 4D RBE-weighted doses.