452 research outputs found

    Impact of 5-formylcytosine on the melting kinetics of DNA by 1H NMR chemical exchange

    Get PDF
    5-Formylcytosine (5fC) is a chemically edited, naturally occurring nucleobase which appears in the context of modified DNA strands. The understanding of the impact of 5fC on dsDNA physical properties is to date limited. In this work, we applied temperature-dependent 1H Chemical Exchange Saturation Transfer (CEST) NMR experiments to non-invasively and site-specifically measure the thermodynamic and kinetic influence of formylated cytosine nucleobase on the melting process involving dsDNA. Incorporation of 5fC within symmetrically positioned CpG sites destabilizes the whole dsDNA structure—as witnessed from the ∼2°C decrease in the melting temperature and 5–10 kJ mol−1 decrease in ΔG°—and affects the kinetic rates of association and dissociation. We observed an up to ∼5-fold enhancement of the dsDNA dissociation and an up to ∼3-fold reduction in ssDNA association rate constants, over multiple temperatures and for several proton reporters. Eyring and van’t Hoff analysis proved that the destabilization is not localized, instead all base-pairs are affected and the transition states resembles the single-stranded conformation. These results advance our knowledge about the role of 5fC as a semi-permanent epigenetic modification and assist in the understanding of its interactions with reader proteins

    Laser-Driven Rayleigh-Taylor Instability: Plasmonics Effects and Three-Dimensional Structures

    Full text link
    The acceleration of dense targets driven by the radiation pressure of high-intensity lasers leads to a Rayleigh-Taylor instability (RTI) with rippling of the interaction surface. Using a simple model it is shown that the self-consistent modulation of the radiation pressure caused by a sinusoidal rippling affects substantially the wavevector spectrum of the RTI depending on the laser polarization. The plasmonic enhancement of the local field when the rippling period is close to a laser wavelength sets the dominant RTI scale. The nonlinear evolution is investigated by three dimensional simulations, which show the formation of stable structures with "wallpaper" symmetry.Comment: 5 pages, 5 figures. New version includes 2D and 3D simulations. More details in the analytical calculation are given in the previous versio

    Principle-based structured case discussions: do they foster moral competence in medical students?

    Get PDF
    BACKGROUND: Recent findings suggest that medical students' moral competence decreases throughout medical school. This pilot study gives preliminary insights into the effects of two educational interventions in ethics classes on moral competence among medical students in Munich, Germany. METHODS: Between 2012 and 2013, medical students were tested using Lind's Moral Competence Test (MCT) prior to and after completing different ethics classes. The experimental group (EG, N = 76) participated in principle-based structured case discussions (PBSCDs) and was compared with a control group with theory-based case discussions (TBCDs) (CG, N = 55). The pre/post C-scores were compared using a Wilcoxon Test, ANOVA and effect-size calculation. RESULTS: The C-score improved by around 3.2 C-points in the EG, and by 0.2 C-points in the CG. The mean C-score difference was not statistically significant for the EG (P = 0.14) or between the two groups (P = 0.34). There was no statistical significance for the teachers' influence (P = 0.54) on C-score. In both groups, students with below-average (M = 29.1) C-scores improved and students with above-average C-scores regressed. The increase of the C-Index was greater in the EG than in the CG. The absolute effect-size of the EG compared with the CG was 3.0 C-points, indicating a relevant effect. CONCLUSION: Teaching ethics with PBSCDs did not provide a statistically significant influence on students' moral competence, compared with TBCDs. Yet, the effect size suggests that PBSCDs may improve moral competence among medical students more effectively. Further research with larger and completely randomized samples is needed to gain definite explanations for the results

    Principle-based structured case discussions: do they foster moral competence in medical students?

    Get PDF
    BACKGROUND: Recent findings suggest that medical students' moral competence decreases throughout medical school. This pilot study gives preliminary insights into the effects of two educational interventions in ethics classes on moral competence among medical students in Munich, Germany. METHODS: Between 2012 and 2013, medical students were tested using Lind's Moral Competence Test (MCT) prior to and after completing different ethics classes. The experimental group (EG, N = 76) participated in principle-based structured case discussions (PBSCDs) and was compared with a control group with theory-based case discussions (TBCDs) (CG, N = 55). The pre/post C-scores were compared using a Wilcoxon Test, ANOVA and effect-size calculation. RESULTS: The C-score improved by around 3.2 C-points in the EG, and by 0.2 C-points in the CG. The mean C-score difference was not statistically significant for the EG (P = 0.14) or between the two groups (P = 0.34). There was no statistical significance for the teachers' influence (P = 0.54) on C-score. In both groups, students with below-average (M = 29.1) C-scores improved and students with above-average C-scores regressed. The increase of the C-Index was greater in the EG than in the CG. The absolute effect-size of the EG compared with the CG was 3.0 C-points, indicating a relevant effect. CONCLUSION: Teaching ethics with PBSCDs did not provide a statistically significant influence on students' moral competence, compared with TBCDs. Yet, the effect size suggests that PBSCDs may improve moral competence among medical students more effectively. Further research with larger and completely randomized samples is needed to gain definite explanations for the results

    Epigenetically modified nucleobases: characterization of structure and dynamics

    Get PDF

    Point-of-Care Ultrasound Assessment of Tropical Infectious Diseases—A Review of Applications and Perspectives

    Get PDF
    The development of good quality and affordable ultrasound machines has led to the establishment and implementation of numerous point-of-care ultrasound (POCUS) protocols in various medical disciplines. POCUS for major infectious diseases endemic in tropical regions has received less attention, despite its likely even more pronounced benefit for populations with limited access to imaging infrastructure. Focused assessment with sonography for HIV-associated TB (FASH) and echinococcosis (FASE) are the only two POCUS protocols for tropical infectious diseases, which have been formally investigated and which have been implemented in routine patient care today. This review collates the available evidence for FASH and FASE, and discusses sonographic experiences reported for urinary and intestinal schistosomiasis, lymphatic filariasis, viral hemorrhagic fevers, amebic liver abscess, and visceral leishmaniasis. Potential POCUS protocols are suggested and technical as well as training aspects in the context of resource-limited settings are reviewed. Using the focused approach for tropical infectious diseases will make ultrasound diagnosis available to patients who would otherwise have very limited or no access to medical imaging
    • …
    corecore