dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae

We identified a viable allele (dut1-1) of the DUT1 gene that encodes the dUTPase activity in Saccharomyces cerevisiae. The Dut1-1 protein possesses a single amino acid substitution (Gly82Ser) in a conserved motif nearby the active site and exhibits a greatly reduced dUTPase activity. The dut1-1 single mutant exhibits growth delay and cell cycle abnormalities and shows a strong spontaneous mutator phenotype. All phenotypes of the dut1-1 mutant are suppressed by the simultaneous inactivation of the uracil DNA N-glycosylase, Ung1. However, the ung1 dut1-1 double mutant accumulates uracil in its genomic DNA. The viability of the dut1-1 mutant is greatly impaired by the simultaneous inactivation of AP endonucleases. These data strongly suggest that the phenotypes of the dut1-1 mutant result from the incorporation of dUMPs into DNA subsequently converted into AP sites. The analysis of the dut1-1 strain mutation spectrum showed that cytosines are preferentially incorporated in front of AP sites in a Rev3-dependent manner during translesion synthesis. These results point to a critical role of the Dut1 protein in the maintenance of the genetic stability. Therefore, the normal cellular metabolism, and not only its byproducts, is an important source of endogenous DNA damage and genetic instability in eukaryotic cells

Psychological Balance in High Level Athletes: Gender-Based Differences and Sport-Specific Patterns

OBJECTIVES: Few epidemiological studies have focused on the psychological health of high level athletes. This study aimed to identify the principal psychological problems encountered within French high level athletes, and the variations in their prevalence based on sex and the sport practiced. METHODS: Multivariate analyses were conducted on nationwide data obtained from the athletes' yearly psychological evaluations. RESULTS: A representative sample of 13% of the French athlete population was obtained. 17% of athletes have at least one ongoing or recent disorder, generalized anxiety disorder (GAD) being the most prevalent (6%), followed by non-specific eating disorders (4.2%). Overall, 20.2% of women had at least one psychopathology, against 15.1% in men. This female predominance applied to anxiety and eating disorders, depression, sleep problems and self-harming behaviors. The highest rates of GAD appeared in aesthetic sports (16.7% vs. 6.8% in other sports for men and 38.9% vs. 10.3% for women); the lowest prevalence was found in high risk sports athletes (3.0% vs. 3.5%). Eating disorders are most common among women in racing sports (14% vs. 9%), but for men were found mostly in combat sports (7% vs. 4.8%). DISCUSSION: This study highlights important differences in psychopathology between male and female athletes, demonstrating that the many sex-based differences reported in the general population apply to elite athletes. While the prevalence of psychological problems is no higher than in the general population, the variations in psychopathology in different sports suggest that specific constraints could influence the development of some disorders

Anomalous nonlinear X-ray Compton scattering

X-ray scattering is typically used as a weak linear atomic-scale probe of matter. At high intensities, such as produced at free-electron lasers, nonlinearities can become important, and the probe may no longer be considered weak. Here we report the observation of one of the most fundamental nonlinear X-ray–matter interactions: the concerted nonlinear Compton scattering of two identical hard X-ray photons producing a single higher-energy photon. The X-ray intensity reached 4 × 1020 W cm−2, corresponding to an electric field well above the atomic unit of strength and within almost four orders of magnitude of the quantum-electrodynamic critical field. We measure a signal from solid beryllium that scales quadratically in intensity, consistent with simultaneous non-resonant two-photon scattering from nearly-free electrons. The high-energy photons show an anomalously large redshift that is incompatible with a free-electron approximation for the ground-state electron distribution, suggesting an enhanced nonlinearity for scattering at large momentum transfer

Anomalous nonlinear X-ray Compton scattering

X-ray scattering is typically used as a weak linear atomic-scale probe of matter. At high intensities, such as produced at free-electron lasers, nonlinearities can become important, and the probe may no longer be considered weak. Here we report the observation of one of the most fundamental nonlinear X-ray–matter interactions: the concerted nonlinear Compton scattering of two identical hard X-ray photons producing a single higher-energy photon. The X-ray intensity reached 4 × 1020 W cm−2, corresponding to an electric field well above the atomic unit of strength and within almost four orders of magnitude of the quantum-electrodynamic critical field. We measure a signal from solid beryllium that scales quadratically in intensity, consistent with simultaneous non-resonant two-photon scattering from nearly-free electrons. The high-energy photons show an anomalously large redshift that is incompatible with a free-electron approximation for the ground-state electron distribution, suggesting an enhanced nonlinearity for scattering at large momentum transfer

Simultaneous Bright- and Dark-Field X-ray Microscopy at X-ray Free Electron Lasers

The structures, strain fields, and defect distributions in solid materials underlie the mechanical and physical properties across numerous applications. Many modern microstructural microscopy tools characterize crystal grains, domains and defects required to map lattice distortions or deformation, but are limited to studies of the (near) surface. Generally speaking, such tools cannot probe the structural dynamics in a way that is representative of bulk behavior. Synchrotron X-ray diffraction based imaging has long mapped the deeply embedded structural elements, and with enhanced resolution, Dark Field X-ray Microscopy (DFXM) can now map those features with the requisite nm-resolution. However, these techniques still suffer from the required integration times due to limitations from the source and optics. This work extends DFXM to X-ray free electron lasers, showing how the $10^{12}$ photons per pulse available at these sources offer structural characterization down to 100 fs resolution (orders of magnitude faster than current synchrotron images). We introduce the XFEL DFXM setup with simultaneous bright field microscopy to probe density changes within the same volume. This work presents a comprehensive guide to the multi-modal ultrafast high-resolution X-ray microscope that we constructed and tested at two XFELs, and shows initial data demonstrating two timing strategies to study associated reversible or irreversible lattice dynamics