Moskau und Petersburg in der russischen Literatur (ca. 1700-1850)

In der Reihe Slavistische Beiträge werden vor allem slavistische Dissertationen des deutschsprachigen Raums sowie vereinzelt auch amerikanische, englische und russische publiziert. Darüber hinaus stellt die Reihe ein Forum für Sammelbände und Monographien etablierter Wissenschafter/innen dar

Molecular Characterization of Embryonic Stem Cell-Derived Cardiac Neural Crest-Like Cells Revealed a Spatiotemporal Expression of an Mlc-3 Isoform

Background and Objectives: Pluripotent embryonic stem (ES) cells represent a perfect model system for the investigation of early developmental processes. Besides their differentiation into derivatives of the three primary germ layers, they can also be differentiated into derivatives of the ‘fourth’ germ layer, the neural crest (NC). Due to its multipotency, extensive migration and outstanding capacity to generate a remarkable number of different cell types, the NC plays a key role in early developmental processes. Cardiac neural crest (CNC) cells are a subpopulation of the NC, which are of crucial importance for precise cardiovascular and pharyngeal glands’ development. CNC-associated malformations are rare, but always severe and life-threatening. Appropriate cell models could help to unravel underlying pathomechanisms and to develop new therapeutic options for relevant heart malformations. Methods: Murine ES cells were differentiated according to a mesodermal-lineage promoting protocol. Expression profiles of ES cell-derived progeny at various differentiation stages were investigated on transcript and protein level. Results: Comparative expression profiling of murine ES cell multilineage progeny versus undifferentiated ES cells confirmed differentiation into known cell derivatives of the three primary germ layers and provided evidence that ES cells have the capacity to differentiate into NC/CNC-like cells. Applying the NC/CNC cell-specific marker, 4E9R, an unambiguous identification of ES cell-derived NC/CNC-like cells was achieved. Conclusions: Our findings will facilitate the establishment of an ES cell-derived CNC cell model for the investigation of molecular pathways during cardiac development in health and disease

Oligocene and early Miocene mammal biostratigraphy of the Valley of Lakes in Mongolia

The Taatsiin Gol Basin in Mongolia is a key area for understanding the evolution and dispersal of Central Asian mammal faunas during the Oligocene and early Miocene. After two decades of intense fieldwork, the area is extraordinarily well sampled and taxonomically well studied, yielding a large dataset of 19,042 specimens from 60 samples. The specimens represent 176 species-level and 99 genus-level taxa comprising 135 small mammal species and 47 large mammals. A detailed lithostratigraphy and new magnetostratigraphic and radiometric datings provide an excellent frame for these biotic data. Therefore, we test and evaluate the informal biozonation scheme that has been traditionally used for biostratigraphic correlations within the basin. Based on the analysis of the huge dataset, a formalised biostratigraphic scheme is proposed. It comprises the Cricetops dormitor Taxon Range Zone (Rupelian), subdivided into the Allosminthus khandae Taxon Range Subzone and the Huangomys frequens Abundance Subzone, the Amphechinus taatsiingolensis Abundance Zone (early Chattian), the Amphechinus major Taxon Range Zone (late Chattian), subdivided into the Yindirtemys deflexus Abundance Subzone and the Upper Amphechinus major T. R. Z., and the Tachyoryctoides kokonorensis Taxon Range Zone (Aquitanian). In statistical analyses, samples attributed to these biozones form distinct clusters, indicating that each biozone was also characterised by a distinct faunal type

A G316A polymorphism in the ornithine decarboxylase gene promoter modulates MYCN-driven childhood neuroblastoma

Simple Summary Neuroblastoma is a devasting childhood cancer in which multiple copies (amplification) of the cancer-causing gene MYCN strongly predict poor outcome. Neuroblastomas are reliant on high levels of cellular components called polyamines for their growth and malignant behavior, and the gene regulating polyamine synthesis is called ODC1. ODC1 is often coamplified with MYCN, and in fact is regulated by MYCN, and like MYCN is prognostic of poor outcome. Here we studied a naturally occurring genetic variant or polymorphism that occurs in the ODC1 gene, and used gene editing to demonstrate the functional importance of this variant in terms of ODC1 levels and growth of neuroblastoma cells. We showed that this variant impacts the ability of MYCN to regulate ODC1, and that it also influences outcome in neuroblastoma, with the rarer variant associated with a better survival. This study addresses the important topic of genetic polymorphisms in cancer. Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein

Preliminary results on the suppression of sensing cross-talk in LISA Pathfinder

In the original paper describing the first measurements performed with LISA Pathfinder, a bulge in the acceleration noise was shown in the 200 mHz - 20 mHz frequency band. This bulge noise originated from cross-coupling of spacecraft motion into the longitudinal readout and it was shown that it is possible to subtract this cross-talk noise. We discuss here the model that was used for subtraction as well as an alternative approach to suppress the cross talk by realignment of the test masses. Such a realignment was performed after preliminary analysis of a dedicated cross-talk experiment, and we show the resulting noise suppression. Since then, further experiments have been performed to investigate the cross-coupling behaviour, however analysis of these experiments is still on-going

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention