Omics assisted N-terminal proteoform and protein expression profiling on methionine aminopeptidase 1 (MetAP1) deletion

Excision of the N-terminal initiator methionine (iMet) residue from nascent peptide chains is an essential and omnipresent protein modification carried out by methionine aminopeptidases (MetAPs) that accounts for a major source of N-terminal proteoform diversity. Although MetAP2 is known to be implicated in processes such as angiogenesis and proliferation in mammals, the physiological role of MetAP1 is much less clear. In this report we studied the omics-wide effects of human MetAP1 deletion and general MetAP inhibition. The levels of iMet retention are inversely correlated with cellular proliferation rates. Further, despite the increased MetAP2 expression on MetAP1 deletion, MetAP2 was unable to restore processing of Met-Ser-, Met-Pro-, and Met-Ala- starting N termini as inferred from the iMet retention profiles observed, indicating a higher activity of MetAP1 over these N termini. Proteome and transcriptome expression profiling point to differential expression of proteins implicated in lipid metabolism, cytoskeleton organization, cell proliferation and protein synthesis upon perturbation of MetAP activity

Bacterial riboproteogenomics : the era of N-terminal proteoform existence revealed

With the rapid increase in the number of sequenced prokaryotic genomes, relying on automated gene annotation became a necessity. Multiple lines of evidence, however, suggest that current bacterial genome annotations may contain inconsistencies and are incomplete, even for so-called well-annotated genomes. We here discuss underexplored sources of protein diversity and new methodologies for high-throughput genome re-annotation. The expression of multiple molecular forms of proteins (proteoforms) from a single gene, particularly driven by alternative translation initiation, is gaining interest as a prominent contributor to bacterial protein diversity. In consequence, riboproteogenomic pipelines were proposed to comprehensively capture proteoform expression in prokaryotes by the complementary use of (positional) proteomics and the direct readout of translated genomic regions using ribosome profiling. To complement these discoveries, tailored strategies are required for the functional characterization of newly discovered bacterial proteoforms

Diverse roles of Dpb2, the non-catalytic subunit of DNA polymerase ε

Timely progression of living cells through the cell cycle is precisely regulated. This involves a series of phosphorylation events which are regulated by various cyclins, activated in coordination with the cell cycle progression. Phosphorylated proteins govern cell growth, division as well as duplication of the genetic material and transcriptional activation of genes involved in these processes. A subset of these tightly regulated genes, which depend on the MBF transcription factor and are mainly involved in DNA replication and cell division, is transiently activated at the transition from G1 to S phase. A Saccharomyces cerevisiae mutant in the Dpb2 non-catalytic subunit of DNA polymerase ε (Polε) demonstrates abnormalities in transcription of MBF-dependent genes even in normal growth conditions. It is, therefore, tempting to speculate that Dpb2 which, as described previously, participates in the early stages of DNA replication initiation, has an impact on the regulation of replication-related genes expression with possible implications for genomic stability

eIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs

Alternative translation initiation mechanisms such as leaky scanning and reinitiation potentiate the polycistronic nature of human transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stimuli. We combined proteomics with ribosome profiling and mRNA sequencing to identify the biological targets of translation control triggered by the eukaryotic translation initiation factor 1 (eIF1), a protein implicated in the stringency of start codon selection. We quantified expression changes of over 4000 proteins and 10 000 actively translated transcripts, leading to the identification of 245 transcripts undergoing translational control mediated by upstream open reading frames (uORFs) upon eIF1 deprivation. Here, the stringency of start codon selection and preference for an optimal nucleotide context were largely diminished leading to translational upregulation of uORFs with suboptimal start. Interestingly, genes affected by eIF1 deprivation were implicated in energy production and sensing of metabolic stress

Die Bewältigung kultureller Differenezen im interkulturellen Management am Beispiel Polens

Die vorliegende Arbeit zeigt die große Bedeutung der interkulturellen Kompetenzen im internationalen Management. Im Zeitalter der Globalisierung und Internationalisierung, wo grenzüberschreitende wirtschaftliche Aktivitäten und internationale Kooperationen zum Alltag gehören, verdient die Kulturproblematik größere Aufmerksamkeit. Denn die internationalen Geschäftskontakte werden nur im weiteren Sinne von Unternehmen und Organisationen und in erster Linie von den Menschen unterhalten. Das Wissen über die kulturellen Hintergründe der ausländischen Interaktionspartner und ihr Werte-und Normensystem, das sich in bestimmten Verhaltensweisen manifestiert, hilft unnötige Missverständnisse und Missinterpretationen in der Kommunikation zu vermeiden. Dies führt schließlich zur besseren Verständigung der Vertreter der beiden Kulturen und zur erfolgreichen Zusammenarbeit. Diese Problematik wurde in der vorliegenden Arbeit am Beispiel Polens gezeigt. Es wurden die wichtigsten Charakteristika der polnischen Kultur (Nation) analysiert und erklärt und auch Konfliktpotenziale in der Zusammenarbeit mit anderen Kulturen aufgedeckt. Dabei wurden als Vergleichskulturen Österreich und Deutschland, als wichtige wirtschaftliche Partner Polens ausgewählt. Es wurde auch mögliche Lösungsvorschläge zur Überwindung kultureller Differenzen gemacht und im Allgemeinen darauf hingewiesen, dass kulturelle Sensibilität und Aufgeschlossenheit, sowie Vermeidung von Vorurteilen und Stereotypen für die interkulturelle Tätigkeit, besonders bei den Führungskräften zum Erfolg beim Auslandseinsatz verhilft.The aim of this project is to highlight the importance of the observation of cultural differences for the area of intercultural management. As demonstrated by several studies about intercultural management, many co-operations fail due to the insufficient intercultural competence of the participants. But differences in mentality don’t necessarily have to lead to problems and obstacles in international co-operations. On the contrary, the correct approach to cultural diversity can also create positive synergy effects. In this project, in the context of the creation of solution strategies for the management of intercultural differences, intercultural contacts in Poland were taken into consideration with two specific national cultures – Germany and Austria. An analysis of the Polish cultural characteristics and the Polish system of values and norms which have the greatest influence on and most affects the conduct of Polish people in terms of their intercultural contacts was carried out in the course of this essay. During the description of the Polish cultural particularities, potential conflicts in terms of the intercultural co-operation with the Germans and Austrians were also highlighted and described, and finally, specific suggestions were made about the management of the cultural differences

Review of guidelines for the intellectual capital statement : how to manage and communicate the company's knowledge

We have entered the Knowledge Era in which the basic economic resource is knowledge, also called Intellectual Capital (IC}. In order to effectively manage companies that are increasingly based on intangibles, it is necessary to measure these resources. Moreover, once measured, the effects should be communicated, as measurement without any further action has no sense. Most of the resources that create value for a company are totally omitted or under-evaluated by accounting; therefore, they are beyond control and beyond management. The most important way to overcome this problem is to implement an IC statement that visualizes the actions and their effects concerning the development of a company's knowledge resources and value creation. This paper aims to analyze the development of guidelines on the Intellectual Capital (IC) Statement by providing a comparison of existing guidelines and presenting their significance