Investigation of pathomechanisms in Parkinson’s disease mouse models

Morbus Parkinson (PD) ist eine unheilbare, neurodegenerative Erkrankung. Die Ursachen dieser Erkrankungen sind nicht geklärt, aber es konnten Genmutationen im Parkin oder $\alpha$ Synuclein Gen identifiziert werden, die zu Parkinson führen. Darauf basierend wurden vom Lehrstuhl für Tierphysiologie Mausmodelle erzeugt, um die Mechanismen dieser Erkrankung zu untersuchen. Dafür wurde eine zuvor durchgeführte Transkriptionsanalyse dieser Mausmodelle neu ausgewertet. Dadurch wurden 150 Gene identifiziert und mit einer unabhängigen Methode überprüft, was zu der Identifizierung des Calcium-bindenden ER Proteins Reticulocalbin (Rcn1) führte. Daraufhin wurde in deren Astrozyten ein reduzierter Calcium Ausstrom gemessen, der auf der veränderten Rcn1 Expression basiert. Daraus folgt, dass Rcn1 verantwortlich für die reduzierte Calcium Antwort in Padel Astrozyten ist und damit das erste bekannte Protein darstellt, welches Parkin-abhängig die Calcium Dynamik im endoplasmatischen Retikulum reguliert

Radiostratigraphy and age structure of the Greenland Ice Sheet

©2015. The Authors. Several decades of ice-penetrating radar surveys of the Greenland and Antarctic ice sheets have observed numerous widespread internal reflections. Analysis of this radiostratigraphy has produced valuable insights into ice sheet dynamics and motivates additional mapping of these reflections. Here we present a comprehensive deep radiostratigraphy of the Greenland Ice Sheet from airborne deep ice-penetrating radar data collected over Greenland by The University of Kansas between 1993 and 2013. To map this radiostratigraphy efficiently, we developed new techniques for predicting reflection slope from the phase recorded by coherent radars. When integrated along track, these slope fields predict the radiostratigraphy and simplify semiautomatic reflection tracing. Core-intersecting reflections were dated using synchronized depth-age relationships for six deep ice cores. Additional reflections were dated by matching reflections between transects and by extending reflection-inferred depth-age relationships using the local effective vertical strain rate. The oldest reflections, dating to the Eemian period, are found mostly in the northern part of the ice sheet. Within the onset regions of several fast-flowing outlet glaciers and ice streams, reflections typically do not conform to the bed topography. Disrupted radiostratigraphy is also observed in a region north of the Northeast Greenland Ice Stream that is not presently flowing rapidly. Dated reflections are used to generate a gridded age volume for most of the ice sheet and also to determine the depths of key climate transitions that were not observed directly. This radiostratigraphy provides a new constraint on the dynamics and history of the Greenland Ice Sheet

Radiostratigraphy and age structure of the Greenland Ice Sheet

©2015. The Authors. Several decades of ice-penetrating radar surveys of the Greenland and Antarctic ice sheets have observed numerous widespread internal reflections. Analysis of this radiostratigraphy has produced valuable insights into ice sheet dynamics and motivates additional mapping of these reflections. Here we present a comprehensive deep radiostratigraphy of the Greenland Ice Sheet from airborne deep ice-penetrating radar data collected over Greenland by The University of Kansas between 1993 and 2013. To map this radiostratigraphy efficiently, we developed new techniques for predicting reflection slope from the phase recorded by coherent radars. When integrated along track, these slope fields predict the radiostratigraphy and simplify semiautomatic reflection tracing. Core-intersecting reflections were dated using synchronized depth-age relationships for six deep ice cores. Additional reflections were dated by matching reflections between transects and by extending reflection-inferred depth-age relationships using the local effective vertical strain rate. The oldest reflections, dating to the Eemian period, are found mostly in the northern part of the ice sheet. Within the onset regions of several fast-flowing outlet glaciers and ice streams, reflections typically do not conform to the bed topography. Disrupted radiostratigraphy is also observed in a region north of the Northeast Greenland Ice Stream that is not presently flowing rapidly. Dated reflections are used to generate a gridded age volume for most of the ice sheet and also to determine the depths of key climate transitions that were not observed directly. This radiostratigraphy provides a new constraint on the dynamics and history of the Greenland Ice Sheet

A shedding analysis after AAV8 CNS injection revealed fragmented viral DNA without evidence of functional AAV particles in mice

Adeno-associated viruses (AAV) are commonly used in the scientific field due to their diverse application range. However, AAV shedding, the release of virions from the host organism, can impact the safety of AAV-based approaches. An increasing number of authorities require the characterization of vector shedding in clinical trials. Recently, shedding of transduced laboratory animals has also gained attention regarding the necessary disposal measures of their waste products. However, no explicit international regulations for AAV-shedding waste exist. Generating insights into shedding dynamics becomes increasingly relevant to help authorities develop adequate regulations. To date, knowledge of AAV vector shedding in mice is very limited. Moreover, confirmation of functional shed AAV particles in mice is missing. Therefore, we examined feces, urine, and saliva of mice after CNS injection with AAV2/8. It revealed the presence of viral DNA fragments via qPCR for up to 4 days after injection. To examine AAV functionality we performed nested PCR and could not detect full-length viral genomes in any but two collected feces samples. Furthermore, a functional infection assay did not reveal evidence of intact AAV particles. Our findings are supposed to contribute murine shedding data as a foundation to help establish still lacking adequate biosafety regulations in the context of AAV shedding