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Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans. © 2020 Federation of American Societies for Experimental Biology.Nonalcoholic fatty liver disease is a chronic liver disease which is associated with obesity and insulin resistance. We investigated the implication of REDD1 (Regulated in development and DNA damage response-1), a stress-induced protein in the development of hepatic steatosis. REDD1 expression was increased in the liver of obese mice and morbidly obese patients, and its expression correlated with hepatic steatosis and insulin resistance in obese patients. REDD1 deficiency protected mice from the development of hepatic steatosis induced by high-fat diet (HFD) without affecting body weight gain and glucose intolerance. This protection was associated with a decrease in the expression of lipogenic genes, SREBP1c, FASN, and SCD-1 in liver of HFD-fed REDD1-KO mice. Healthy mitochondria are crucial for the adequate control of lipid metabolism and failure to remove damaged mitochondria is correlated with liver steatosis. Expression of markers of autophagy and mitophagy, Beclin, LC3-II, Parkin, BNIP3L, was enhanced in liver of HFD-fed REDD1-KO mice. The number of mitochondria showing colocalization between LAMP2 and AIF was increased in liver of HFD-fed REDD1-KO mice. Moreover, mitochondria in liver of REDD1-KO mice were smaller than in WT. These results are correlated with an increase in PGC-1α and CPT-1 expression, involved in fatty acid oxidation. In conclusion, loss of REDD1 protects mice from the development of hepatic steatosis. © 2020 Federation of American Societies for Experimental Biology.OBJECTIVES Teaching intimate examinations to medical students has been recognized as difficult because of the anxious feelings that the students may experience. For their professional development, previously incorporated understandings need to be relearned how to transgress boundaries that regulate intimacy and physical closeness, learning to examine and touch other peoples' bodies, and talking about things that are otherwise taboo. This paper compares how students learn to perform two intimate examinations - the digital rectal exam of the prostate (DRE) and the bimanual pelvic exam (PE) - and analyses how norms and expectations affect how students learn to approach them. METHODS This study is based on ethnographic work in-depth qualitative interviews with two urologists and nine medical students in semesters 4, 8 and 11 of a medical education programme in Sweden, observations of three learning sessions where 16 students performed the PE on professional patients, and two days of observations at a urology out-rights reserved.Engaging in exercise while undergoing radiotherapy (RT) has been reported to be safe and achievable. The impact of exercise training (ET) on RT efficiency is however largely unknown. Our study aims to investigate the interactions between ET and RT on prostate cancer growth. Athymic mice received a subcutaneous injection of PPC-1 cells and were randomly assigned to either cancer control, cancer ET, cancer RT, or cancer RT combined with ET (CaRT-ET). Mice were sacrificed 24 days post-injection. All three intervention groups had reduced tumor size, the most important decrease being observed in CaRT-ET mice. Apoptotic marker cleaved caspase-3 was not modified by ET, but enhanced with RT. Importantly, this increase was the highest when the two strategies were combined. Furthermore, NK1.1 staining and gene expression of natural killer (NK) cell receptors Klrk1 and Il2rβ were not affected by ET alone but were increased with RT, this effect being potentiated when combined with ET. Overall, our study shows that (a) ET enhances RT efficiency by potentiating NK cell infiltration, and (b) while ET alone and ET combined with RT both reduce tumor growth, the mechanisms mediating these effects are different. © 2020 Federation of American Societies for Experimental Biology.Gene-set analyses are used to assess whether there is any evidence of association with disease among a set of biologically related genes. Such an analysis typically treats all genes within the sets similarly, even though there is substantial, external, information concerning the likely importance of each gene within each set. For example, for traits that are under purifying selection, we would expect genes showing extensive genic constraint to be more likely to be trait associated than unconstrained genes. Here we improve gene-set analyses by incorporating such external information into a higher-criticism-based signal detection analysis. We show that when this external information is predictive of whether a gene is associated with disease, our approach can lead to a significant increase in power. Further, our approach is particularly powerful when the signal is sparse, that is when only a small number of genes within the set are associated with the trait. We illustrate our approach with a gene-set analysis of amyotrophic lateral sclerosis (ALS) and implicate a number of gene-sets containing SOD1 and NEK1 as well as showing enrichment of small p values for gene-sets containing known ALS genes. We implement our approach in the R package wHC. © 2020 Wiley Periodicals, Inc.Vacuoles are useful materials with antimicrobial and anticancerous properties. Vacuolar proteins can discompose macromolecules from the outside of yeast cells. The objective of this study was to determine the function of a protein transported into a vacuole. Specifically, cytosolic protein aldehyde dehydrogenase 6 (ALD6) was used for the delivery to the vacuole. To transport cytosolic protein to the vacuole in this study, a transfer vector including a signal peptide sequence isolated from vacuolar protein proteinase A was designed. A signal peptide is an amino acid sequence in front of the transported protein. Signal peptides have various delivery pathways according to the kind of signal sequence they contain. They play important roles in transporting proteins to organelles, in cellular mechanisms, and the transfer of protein outside and inside eukaryotes. Thus, we focused on the design of a transfer vector containing a signal peptide sequence isolated from the DNA sequence of proteinase A (PEP4). Trichostatin A solubility dmso In addition, this study evaluated the expression level of cytosolic ALD6 after being transported into the yeast vacuole. Our results showed that the developed transfer vector was useful for delivering proteins to vacuole by using signal peptide sequence. Therefore, this transfer vector might be used as a tool to deliver target proteins to organelles of interest in eukaryotes. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The expected imminent widespread use of electromobility in transport systems draws attention to the possible effects of human exposure to magnetic fields generated inside electric vehicles and during their recharge. The current trend is to increase the capacity of the battery inside the vehicles to extend the available driving range and to increase the power of recharging columns to reduce the time required for a full recharge. This leads to higher currents and potentially stronger magnetic fields. The Interoperability Center of the Joint Research Center started an experimental activity focused on the assessment of low-frequency magnetic fields emitted by five fast-charging devices available on the market in recharge and standby conditions. The aim of this study was to contribute to the development of a standard measurement procedure for the assessment of magnetic fields emitted by direct current charging columns. The spectrum and amplitudes of the magnetic field, as well as exposure indices according to guidelines for the general public and occupational exposure, were recorded by means of a magnetic field probe analyzer. The worst-case scenario for instantaneous physical direct and indirect effects was identified. Measurements within the frequency range of 25 Hz-2 kHz revealed localized magnetic flux density peaks above 100 μT at the 50 Hz frequency in three out of five chargers, registered in close proximity during the recharge. Beyond this distance, exposure indices were recorded showing values below 50% of reference levels. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.The protein and energy requirements of critically ill patients treated in intensive care units (ICUs) have been actively discussed recently. Currently published clinical recommendations and reviews suggest significant increases of protein provision to 2-2.5 g/kg/d in some populations of ICU patients. However, a detailed analysis of the main sources of these recommendations reveals a number of serious contradictions, as well as an absence of obvious evidence supporting the allotment of high doses of protein. We went through these recommendations and reviewed cited articles and other studies, and we have separated our arguments against excessive protein provision into sections. © 2020 American Society for Parenteral and Enteral Nutrition.Some studies have shown that the long-term use of proton pump inhibitors (PPIs) is associated with many adverse events that may increase mortality; however, the relationship between premorbid PPI use and in-hospital mortality has yet to be validated in critically ill patients. Therefore, we performed this study to determine whether the preadmission use of PPIs is associated with mortality in patients admitted to the intensive care unit. This was a retrospective study with a large and freely accessible database in critical-care medicine (the Multiparameter Intelligent Monitoring in Intensive Care III project). The clinical data and outcomes of 17 473 patients, consisting of 1895 in the PPI group, 514 in the H2 -receptor antagonist group, and 15 064 control subjects, were collected during their hospital stay. The study outcome was in-hospital mortality. A total of 17 473 patients were included in our study. PPI use was associated with significantly increased in-hospital mortality in the original model without adjustment for any parameters (odds ratio 1.