Hydroxymethylated Cytosines Are Associated with Elevated C to G Transversion Rates

It has long been known that methylated cytosines deaminate at higher rates than unmodified cytosines and constitute mutational hotspots in mammalian genomes. The repertoire of naturally occurring cytosine modifications, however, extends beyond 5-methylcytosine to include its oxidation derivatives, notably 5-hydroxymethylcytosine. The effects of these modifications on sequence evolution are unknown. Here, we combine base-resolution maps of methyl- and hydroxymethylcytosine in human and mouse with population genomic, divergence and somatic mutation data to show that hydroxymethylated and methylated cytosines show distinct patterns of variation and evolution. Surprisingly, hydroxymethylated sites are consistently associated with elevated C to G transversion rates at the level of segregating polymorphisms, fixed substitutions, and somatic mutations in tumors. Controlling for multiple potential confounders, we find derived C to G SNPs to be 1.43-fold (1.22-fold) more common at hydroxymethylated sites compared to methylated sites in human (mouse). Increased C to G rates are evident across diverse functional and sequence contexts and, in cancer genomes, correlate with the expression of Tet enzymes and specific components of the mismatch repair pathway (MSH2, MSH6, and MBD4). Based on these and other observations we suggest that hydroxymethylation is associated with a distinct mutational burden and that the mismatch repair pathway is implicated in causing elevated transversion rates at hydroxymethylated cytosines

Cultural variability in the effects of question design features on respondent comprehension

Um Charakteristika gleicher Fragen in Gesundheitsumfragen im Zusammenhang mit interkulturellen Unterschieden im Verständnis dieser Fragen zu identifizieren, analysieren die Verfasser Befragungen zum Gesundheitssystem, wobei die Befragten vier verschiedene kulturelle Subgruppen in den USA repräsentieren (weiße Nicht-Hispanics, Afroamerikaner, mexikanische Amerikaner und Puerto Ricaner) mit Hilfe des Instruments des Behaviour Coding. Untersucht werden die Auswirkungen von vier Merkmalen der Fragebogenkonstruktion auf kulturelle Schwierigkeiten beim Verständnis der Fragen. Die empirische Datenbasis bilden 13514 Antworten von 345 Befragten auf 42 Fragen. Es zeigt sich, dass das Antwortformat, die Länge der Frage sowie das Lese- und Abstraktionsniveau der Fragen einen wesentlichen Einfluss auf das Verständnis der Fragen bei den Befragten haben. Die Kultur der Befragen hatte einen moderierenden Einfluss auf die Effekte von Antwortformat, Fragenlänge und Leseniveau. Verschiedene Aspekte des Fragebogendesigns, die den Fragebogen allgemein verständlicher machen sollen, haben ebenfalls kulturspezifische Auswirkungen. (ICEÜbers

Welchen Einfluss hat der Weidegang auf das Tierwohl von Milchkühen? Erste Ergebnisse des Welfare Quality® Protokolls bei ganzjähriger Stallhaltung und Sommerweidegang

Grazing provides livestock better opportunities to act out their species specific behaviour compared to the restrictive stable conditions. Studies on the effect of grazing on animal welfare in dairy farming in Germany are rare and have not been conducted under the specific conditions of organic dairy farming. The aim of the present study was to examine the effects of grazing on animal welfare of dairy cows in organic and conventional farming based on the Welfare Quality® protocol for dairy cattle. In this paper, we present the initial evaluation of a comparison between zero grazing and summer grazing. The first results indicate an improvement in most welfare principles during the summer months for dairy cows with summer grazing, except for between winter and summer in zero grazing farms. In conclusion, grazing offers a great potential for improved animal welfare, while the benefitial effects of grazing are not guaranteed in event of suboptimal management

Surfactant function in lung transplantation after 24 hours of ischemia: Advantage of retrograde flush perfusion for preservation

AbstractObjective: Surfactant function was shown to be impaired in clinical and experimental lung transplantation. This study was designed to define the impact of retrograde flush perfusion on graft and surfactant function after an extended period of ischemia. Methods: Left lung transplantation was performed after 24 hours of graft ischemia in 12 pigs. In half of the grafts antegrade cold flush perfusion (Perfadex) was used for preservation. In the second group grafts were flushed in a retrograde fashion via the left atrium. Graft function was monitored for 7 hours after transplantation. Before transplantation (basal) and after 2 hours of reperfusion, bronchoalveolar lavage fluid was obtained. Minimal surface tension of bronchoalveolar lavage fluid was determined and the ratio of small and large surfactant aggregates was calculated. Lung water content was analyzed online in the reperfusion period. Results: Right-sided heart failure developed in 2 animals of group 1 (antegrade perfusion) within 2 and 4.5 hours of reperfusion, respectively. All other pigs survived the observation period. PO2/FIO2 (P =.001) and dynamic lung compliance (P =.001) were superior in retrogradely flushed grafts. A comparable increase of minimal surface tension was found after reperfusion in both groups. Small/large surfactant aggregate ratio after reperfusion (P =.03), as well as extravascular lung water content, was higher in the antegrade perfusion group. Conclusion: Retrograde flush perfusion for 24-hour lung preservation with low-potassium dextran (Perfadex) solution led to better initial graft function than the standard antegrade perfusion technique. A moderate impairment of surfactant function was found in both groups, which was more pronounced in the antegrade perfusion group

Solidification of small para-H2 clusters at zero temperature

We have determined the ground-state energies of para-H$_2$ clusters at zero temperature using the diffusion Monte Carlo method. The liquid or solid character of each cluster is investigated by restricting the phase through the use of proper importance sampling. Our results show inhomogeneous crystallization of clusters, with alternating behavior between liquid and solid phases up to N=55. From there on, all clusters are solid. The ground-state energies in the range N=13--75 are established and the stable phase of each cluster is determined. In spite of the small differences observed between the energy of liquid and solid clusters, the corresponding density profiles are significantly different, feature that can help to solve ambiguities in the determination of the specific phase of H$_2$ clusters.Comment: 17 pages, accepted for publication in J. Phys. Chem.