Estimating the Phanerozoic history of the Ascomycota lineages : Combining fossil and molecular data

Peer reviewe

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Der Einfluss von MeCP2 auf Barriereeigenschaften der Blut-Hirn Schranke

Das Rett-Syndrom ist eine schwere, progressiv verlaufende neurologische Entwicklungsstörung mit der Prävalenz von 1:15000 in Österreich. Als häufigste Ursache für das klassische Rett-Syndrom wird eine Mutation des Methyl-CpG-bindenden Proteins 2 (MECP2)-Gens beschrieben. MECP2-Mutationen beziehungsweise eine veränderte Expression des MeCP2-Proteins sind jedoch auch mit einem breiten Spektrum von anderen neurologischen Entwicklungsstörungen assoziiert. Da dieses Gen/Protein für eine normale neurologische Entwicklung essentiell ist, wurde in dieser Arbeit versucht, die Auswirkung von MeCP2 auf die Barrierefunktion der Blut-Hirn Schranke zu zeigen. Die Blut-Hirn Schranke stellt eine physiologische Barriere zwischen dem Zentralnervensystem und dem peripheren Blutkreislauf dar und ist deshalb essentiell für die Entwicklung einer normalen Gehirnfunktion. In dieser Arbeit wurde mit MeCP2 knock-out (MeCP2-KO) Mäusen gearbeitet, in denen das MECP2-Gen spezifisch mutiert wurde, was zu einem funktionellen knock-out des Proteins führte. Ein Ziel war die Untersuchung der Auswirkung des MeCP2-KO´s auf die Expression wichtiger Blut-Hirn Schranken Parameter auf Proteinebene. Es konnte keine statistisch signifikante Regulation von Parametern, die für die physikalische Barrierefunktion der Blut-Hirn Schranke essentiell waren, durch den MeCP2-KO beobachtet werden. Die Ergebnisse lassen jedoch vermuten, dass andere Systeme, wie das Transportersystem der Blut-Hirn Schranke, durch den MeCP2-KO reguliert werden könnten. Ein weiteres Ziel der Arbeit war die Entwicklung und Etablierung eines siRNA knock-down Protokolls für MeCP2 in Mausgehirnendothelzellen. Dieses konnte entwickelt werden, in dem ein stabiler knock-down von MeCP2 auf 20-30% erreicht wurde. Dieser siRNA knock-down von MeCP2 führte zu keiner Änderung der untersuchten Blut-Hirn Schranken Marker. Da die Restmenge an MeCP2 jedoch für die normale Funktion der Zelle ausreichen könnte, wäre für die Untersuchung wichtiger Blut-Hirn Schranken Parameter im Zellmodell die Entwicklung eines MeCP2-KO´s in Zellen, beispielweise durch die CRISPR/Cas9-Methode, ein nächster möglicher Schritt.Rett syndrome is a severe, progressive neurodevelopmental disorder with a prevalence of 1:15000 in Austria. The most common cause of classical Rett syndrome is a mutation of the methyl-CpG-binding protein 2 (MECP2) gene. However, MECP2 mutations or altered expression of MeCP2 protein are also associated with a wide range of other neurodevelopmental disorders. Because this gene/protein is essential for normal neurological development, this thesis attempts to demonstrate the effect of MeCP2 on the barrier function of the blood-brain barrier. The blood-brain barrier is a physiological barrier between the central nervous system and the peripheral blood circulation and is essential for the development of normal brain function. In the course of this work MeCP2 knock-out (MeCP2-KO) mice were used, in which the gene was specifically mutated, which led to a functional knock-out of the protein. One aim was to investigate the effect of MeCP2-KO on the expression of important physical blood-brain barrier parameters at the protein level. No statistically significant regulation of these blood-brain barrier parameters was found. However, the results suggested that other properties, such as active transporters, could also be regulated by MeCP2-KO. The second aim of this thesis was the development and establishment of a siRNA knock-down protocol for MeCP2 in mouse brain endothelial cells. A protocol was developed leading to a stable knock-down of MeCP2 to 20-30%. This knock-down did not result in the regulation of tightness markers and suggested that the residual amount of MeCP2 could be sufficient for a normal function of the cell. Further studies might focus on the development of MeCP2-KO cells, by for example CRISPR/Cas9 and the investigation of the regulation of blood-brain barrier properties

Filling a major gap in the LGM chronology of the Eastern Alps: New evidence from Enns and Mur glaciers (Austria)

&amp;lt;p&amp;gt;During the Last Glacial Maximum (LGM), large glacier tongues reached far into the alpine foreland and formed piedmont lobes. Common deposits are moraine &amp;amp;#8220;amphitheatres&amp;amp;#8221; directly connected to glaciofluvial deposits, which are both suitable for (direct) age dating. Over much of the Alpine realm, great efforts have been made to constrain the chronology of the LGM, yet in the eastern part, significant gaps exist, and absolute dates for glacial features are missing. Due to a gradual eastward change in terms of precipitation, moisture, and topography, glaciers did not advance as far in the eastern Alps and terminated in narrow inneralpine valleys. Evidence of their extent is therefore sparse and their deposits were mostly cannibalised by later erosional and depositional processes. Nevertheless, remnant terminal moraines from the Enns and Mur glaciers (mainly fed by the Niedere Tauern in the Central Alps) remain. These deposits contain blocks that can be dated with cosmogenic beryllium and aluminium surface exposure dating.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;For cosmogenic dating, two sites were investigated as follows. The Enns glacier developed north of the Niedere Tauern mountain range and one of its terminal tongues ended at Buchauer Saddle, where a terminal moraine complex is preserved. The moraine ridges reach a few tens of meters in height and contain mostly blocks of carbonate, with some quartz-containing blocks also present. All dated blocks are Palaeozoic quartz conglomerates/breccias, which crop out roughly 25 km upvalley.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;The ice masses of the Mur glacier accumulated south of the Niedere Tauern mountain range in the Mur valley. The glacier was divided into several tongues, one of them terminating near P&amp;amp;#246;ls, where the most prominent moraine of the Mur glacier is preserved. It consists of a diamicton with a silty to clayey matrix and few components of pegmatite gneiss, amphibolite and other crystalline rocks. Datable blocks consist of coarse-grained pegmatite gneiss.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Based on mapping relationships, the spatial context of the both moraine complexes suggest their deposition during the LGM. In this contribution, we will explore this hypothesis so far developed on the basis of field relations by presenting preliminary exposure ages of these landforms.&amp;lt;/p&amp;gt;</jats:p

Rapid Growth of Planktonic Vibrio cholerae Non-O1/Non-O139 Strains in a Large Alkaline Lake in Austria: Dependence on Temperature and Dissolved Organic Carbon Quality▿ †

Vibrio cholerae non-O1/non-O139 strains have caused several cases of ear, wound, and blood infections, including one lethal case of septicemia in Austria, during recent years. All of these cases had a history of local recreational activities in the large eastern Austrian lake Neusiedler See. Thus, a monitoring program was started to investigate the prevalence of V. cholerae strains in the lake over several years. Genetic analyses of isolated strains revealed the presence of a variety of pathogenic genes, but in no case did we detect the cholera toxin gene or the toxin-coregulated pilus gene, both of which are prerequisites for the pathogen to be able to cause cholera. In addition, experiments were performed to elucidate the preferred ecological niche of this pathogen. As size filtration experiments indicated and laboratory microcosms showed, endemic V. cholerae could rapidly grow in a free-living state in natural lake water at growth rates similar to those of the bulk natural bacterial population. Temperature and the quality of dissolved organic carbon had a highly significant influence on V. cholerae growth. Specific growth rates, growth yield, and enzyme activity decreased markedly with increasing concentrations of high-molecular-weight substances, indicating that the humic substances originating from the extensive reed belt in the lake can inhibit V. cholerae growth