Optimal translational termination requires C4 lysyl hydroxylation of eRF1.

Efficient stop codon recognition and peptidyl-tRNA hydrolysis are essential in order to terminate translational elongation and maintain protein sequence fidelity. Eukaryotic translational termination is mediated by a release factor complex that includes eukaryotic release factor 1 (eRF1) and eRF3. The N terminus of eRF1 contains highly conserved sequence motifs that couple stop codon recognition at the ribosomal A site to peptidyl-tRNA hydrolysis. We reveal that Jumonji domain-containing 4 (Jmjd4), a 2-oxoglutarate- and Fe(II)-dependent oxygenase, catalyzes carbon 4 (C4) lysyl hydroxylation of eRF1. This posttranslational modification takes place at an invariant lysine within the eRF1 NIKS motif and is required for optimal translational termination efficiency. These findings further highlight the role of 2-oxoglutarate/Fe(II) oxygenases in fundamental cellular processes and provide additional evidence that ensuring fidelity of protein translation is a major role of hydroxylation.

Detection of counterfeit electronic components through ambient mass spectrometry and chemometrics.

In the last several years, illicit electronic components have been discovered in the inventories of several distributors and even installed in commercial and military products. Illicit or counterfeit electronic components include a broad category of devices that can range from the correct unit with a more recent date code to lower-specification or non-working systems with altered names, manufacturers and date codes. Current methodologies for identification of counterfeit electronics rely on visual microscopy by expert users and, while effective, are very time-consuming. Here, a plasma-based ambient desorption/ionization source, the flowing atmospheric pressure afterglow (FAPA) is used to generate a mass-spectral fingerprint from the surface of a variety of discrete electronic integrated circuits (ICs). Chemometric methods, specifically principal component analysis (PCA) and the bootstrapped error-adjusted single-sample technique (BEAST), are used successfully to differentiate between genuine and counterfeit ICs. In addition, chemical and physical surface-removal techniques are explored and suggest which surface-altering techniques were utilized by counterfeiters.

Racing Clean in a Tainted World: A Qualitative Exploration of the Experiences and Views of Clean British Elite Distance Runners on Doping and Anti-Doping.

Background: Doping has been a prominent issue for the sport of athletics in recent years. The endurance disciplines, which currently account for 56% of the global anti-doping rule violations in athletics, appear to be particularly high risk for doping. Objective: Using this high-risk, high-pressure context, the main purpose of this study was to investigate the human impact of doping and anti-doping on "clean" athletes. The secondary aim of the study was to better understand the reasons for, and barriers to, competing "clean" among this group of athletes. Method: Semi-structured interviews were conducted with 11 elite distance runners from the UK to explore: (1) the reasons and motivations for competing clean. (2) Perceptions of the anti-doping system, and experiences of being part of that system. (3) Views on the prevalence and causes of doping and the impact of doping on the lives of clean athletes. The interviews were audio-recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. Results: Four major themes were identified: (1) The participants in this study have not been tempted to use prohibited substances or methods; they compete in their sport for the personal satisfaction of seeing how good they can be, rather than in pursuit of winning at all costs. (2) Anti-doping does not currently prevent doping effectively and is not implemented evenly across the globe. (3) Doping was perceived as a major issue and was felt to be borne out of certain sporting cultures in which doping is enabled. (4) Doping has impacted the careers of clean athletes in irreversible ways and presents a continuing challenge to the psychological preparation for competition. Conclusions: Clean athletes suffer negative consequences from both doping and anti-doping. ADOs must collaborate across borders to ensure a more even implementation of anti-doping activities, to facilitate a more level playing field on the global stage. ADOs must also acknowledge the existence of a large group of athletes who would never consider deliberately doping and make anti-doping work for these athletes too.

Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells.

Questions about possible adverse health effects from exposures to uranium have arisen as a result of uranium mining, residual mine tailings and use of depleted uranium in the military. The purpose of the current study was to measure the toxicity of depleted uranium as uranyl acetate (UA) in mammalian cells. The activity of UA in the parental CHO AA8 line was compared with that in the XRCC1-deficient CHO EM9 line. Cytotoxicity was measured by clonogenic survival. A dose of 200 microM UA over 24 h produced 3.1-fold greater cell death in the CHO EM9 than the CHO AA8 line, and a dose of 300 microM was 1.7-fold more cytotoxic. Mutagenicity at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus was measured by selection with 6-thioguanine. A dose of 200 microM UA produced approximately 5-fold higher averaged induced mutant frequency in the CHO EM9 line relative to the CHO AA8 line. The generation of DNA strand breaks was measured by the alkaline comet assay at 40 min and 24 h exposures. DNA strand breaks were detected in both lines; however a dose response may have been masked by U-DNA adducts or crosslinks. Uranium-DNA adducts were measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) at 24 and 48 h exposures. A maximum adduct level of 8 U atoms/10(3) DNA-P for the 300 microM dose was found in the EM9 line after 48 h. This is the first report of the formation of uranium-DNA adducts and mutations in mammalian cells after direct exposure to a depleted uranium compound. Data suggest that uranium could be chemically genotoxic and mutagenic through the formation of strand breaks and covalent U-DNA adducts. Thus the health risks for uranium exposure could go beyond those for radiation exposure.