@article{EisenhuthVellmerRauhetal.2021, author = {Eisenhuth, Nicole and Vellmer, Tim and Rauh, Elisa T. and Butter, Falk and Janzen, Christian J.}, title = {A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei}, series = {mbio}, volume = {12}, journal = {mbio}, number = {6}, doi = {10.1128/mBio.01352-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260698}, pages = {e01352-21}, year = {2021}, abstract = {The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation.}, language = {en} } @article{RauchTaubenboeckKnoppetal.2021, author = {Rauch, S. and Taubenb{\"o}ck, H. and Knopp, C. and Rauh, J.}, title = {Risk and space: modelling the accessibility of stroke centers using day- \& nighttime population distribution and different transportation scenarios}, series = {International Journal of Health Geographics}, volume = {20}, journal = {International Journal of Health Geographics}, doi = {10.1186/s12942-021-00284-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261228}, year = {2021}, abstract = {Purpose Rapid accessibility of (intensive) medical care can make the difference between life and death. Initial care in case of strokes is highly dependent on the location of the patient and the traffic situation for supply vehicles. In this methodologically oriented paper we want to determine the inequivalence of the risks in this respect. Methods Using GIS we calculate the driving time between Stroke Units in the district of M{\"u}nster, Germany for the population distribution at day- \& nighttime. Eight different speed scenarios are considered. In order to gain the highest possible spatial resolution, we disaggregate reported population counts from administrative units with respect to a variety of factors onto building level. Results The overall accessibility of urban areas is better than in less urban districts using the base scenario. In that scenario 6.5\% of the population at daytime and 6.8\% at nighttime cannot be reached within a 30-min limit for the first care. Assuming a worse traffic situation, which is realistic at daytime, 18.1\% of the population fail the proposed limit. Conclusions In general, we reveal inequivalence of the risks in case of a stroke depending on locations and times of the day. The ability to drive at high average speeds is a crucial factor in emergency care. Further important factors are the different population distribution at day and night and the locations of health care facilities. With the increasing centralization of hospital locations, rural residents in particular will face a worse accessibility situation.}, language = {en} }