Dynamic interplays between three redox cofactors in a DNA photolyase revealed by spectral decomposition

DNA repair catalyzed by photolyases is accomplished by a light-dependent electron transfer event from a fully reduced flavin adenine dinucleotide to a DNA lesion site. Prokaryotic DNA photolyase, PhrB, possesses a ribolumazine cofactor and a four-iron-four-sulfur cluster in addition to the catalytic flavin, but their functional roles are poorly understood. Here, we employ time-resolved absorption spectroscopy to probe light-induced responses in both solution and single crystals of PhrB. We jointly analyze a large collection of light-induced difference spectra from the wild-type and mutant PhrB obtained under different light and redox conditions. By applying singular value decomposition to 159 time series, we dissect light-induced spectral changes and examine the dynamic interplay between three cofactors. Our findings suggest that these cofactors form an interdependent redox network to coordinate light-induced redox responses. We propose that the ribolumazine cofactor serves as a photoprotective pigment under intense light or prolonged illumination, while the iron-sulfur cluster acts as a transient electron cache to maintain balance between two otherwise independent photoreactions of the flavin and ribolumazine

Dating apps and websites as tools to reach anonymous sexual contacts during an outbreak of hepatitis A among men who have sex with men, Berlin, 2017

Background In an outbreak of hepatitis A among men who have sex with men (MSM) in Berlin (2016 and 2017), patients frequently reported anonymous sex and use of dating applications to meet sexual contacts, hampering tracing and vaccination of contacts. Aim Our objective was to evaluate dating apps and websites as a means of spreading prevention messages among MSM during the ongoing outbreak. Methods Advertisements in different formats were placed on three MSM dating apps and eight websites for anonymous dating during three weeks in March and April 2017. We calculated frequency of ads shown and click-through rates (CTR) and investigated the independent effect of format and platform on the number of clicks using a negative binomial regression model. We evaluated the campaign’s impact using a survey among visitors of a large gay-lesbian street-festival in Berlin. Results Overall, 1,920,180 ads were shown and clicked on 8,831 times (CTR = 0.46%). The multivariable model showed significantly more clicks on one dating app (incidence rate ratio (IRR) = 9.5; 95% confidence interval (CI): 7.7–12.2) than on websites and on full-screen ads (IRR = 3.1; 95% CI: 2.5–3.8) than on banner ads. Of 266 MSM who participated in the survey, 190 (71%) knew about the outbreak and 39 (15%) declared to have been vaccinated recently because of the campaign. Conclusions Dating apps provided a means to rapidly reach and influence a substantial number of MSM in Berlin and should complement case-based contact tracing among MSM in outbreak settings. Clicking on ads depended on platform and format used.Peer Reviewe

Hepatitis A outbreak among MSM in Berlin due to low vaccination coverage: Epidemiology, management, and successful interventions

Objectives To describe the characteristics of a large hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) in Berlin and to assess the impact of measures implemented. Methods Cases of laboratory-confirmed, symptomatic HAV infection notified in Berlin, Germany between August 2016 and February 2018 were analysed using routine and enhanced surveillance data including genotyping results. Several studies involving different groups of participants were conducted to further investigate the outbreak, including surveys on knowledge and practices of HAV vaccination among physicians and vaccination coverage and determinants of vaccination status among MSM. The measures implemented were categorized by target group in a Gantt chart. To assess their impact, health insurance data on HAV vaccination uptake were analysed, comparing Berlin and other federal states. Results During the outbreak period, a total of 222 cases were reported (of which 91 were sequence-confirmed), with a peak in case numbers in January 2017. Physicians were aware of the existing vaccination recommendations, but vaccination coverage among 756 MSM was low, with 32.7% being completely vaccinated and 17.3% being incompletely vaccinated before 2017. HAV vaccination before 2017 was associated with being born in Germany (odds ratio 2.36) and HIV-positive (odds ratio 1.80). HAV monovalent vaccination uptake increased by 164% from 2016 to 2017 among males in Berlin, compared to 7% in other federal states. Conclusions Multiple measures targeting the MSM community, physicians, and public health to increase HAV vaccination uptake were successfully implemented. To prevent future HAV outbreaks, we recommend monitoring vaccination coverage among MSM, promoting awareness of existing recommendations among physicians, and ensuring access for foreign-born and young MSM