Structural and Functional Genomics in Semi-Autonomous Organelles: Composition and Origin of Proteomes of Chloroplasts and Mitochondria and Related Transcriptomics

Mitochondria and chloroplasts are semi-autonomous organelles that have arisen through an endosymbiotic event and, over evolutionary time, have donated most of their genome to the nucleus of the host cell. Due to this transfer of genetic material, the expression of many proteins of the organellar proteomes, now synthesized in the cytosol and re-targeted to the organelles, came under control of the nucleus. Subsequently, means of communication between organelles and nucleus must exist, enabling the organelles to take influence on the nuclear gene expression. This thesis focused on structural and functional genomics in mitochondria and chloroplasts, addressing questions related to the composition, origin and evolution of the organelles, as well as, chloroplast-to-nucleus signaling. The accuracy of five different predictors for the detection of N-terminal targeting peptides was evaluated employing test sets consisting of proteins with experimentally proven subcellular localization, and found to be substantially lower than reported before. Combinations of the predictors showed to be more accurate than any of the predictors alone and were subsequently used to estimate the size and composition of the organellar proteomes. A prediction of the mitochondrial proteomes for ten species was performed and revealed that functional mitochondria harbor from a few hundred to more than 3,000 gene products. A core set of conserved mitochondrial proteins could be identified whose functions are mostly related to transport and metabolism, and -- if mutated -- are frequently associated with disease in humans. In collaboration with W. Martin (Universität Düsseldorf) and co-workers, the cyanobacterial heritage of the Arabidopsis genome was estimated by phylogenetic inferrence and about 4,800 genes (or 18% of the genome) were shown to have been acquired from the prokaryotic ancestor. In both flowering plants, A. thaliana and O. sativa, about 7% of the whole proteome were predicted to be targeted to the chloroplast, with close to 600 of those proteins shared by both species and most likely to be derived from cyanobacteria. The functions of this subset are mainly related to metabolism and energy. In both organelles, species-specific proteins were detected indicating a functional diversification. Even though in A. thaliana the cTP-featuring proteins are predominantly of prokaryotic origin (more than 50%), this indicates that post-endosymbiotic relocations of proteins from/to the chloroplast occurred by altered targeting. These findings were also confirmed for mitochondria. A differential-expression analysis of the nuclear chloroplast transcriptome under 35 environmental and genetic conditions was performed. It revealed, that most of those conditions elicit only three main classes of transcriptome response. Two of these classes, probably involving GUN-type plastid signaling, are characterized by alterations, in opposite directions, in the expression of largely overlapping sets of genes. Thus these findings, suggest the existence of a regulatory, binary master-switch

Big Data Analytics Capabilities: A Systematic Literature Review on Necessary Skills to Succeed in Big Data Analytics

While the amount of data keeps growing, managers ask themselves whether they already retrieve full value from their data. To maximize the value of big data, literature offers first insights in building BDA capabilities (Gupta and George 2016, p; Mikalef et al. 2018). Nevertheless, BDA remains a new field to researchers and companies. BDA frameworks, still offered scarcely, discuss roughly the same dimensions (incorporating some technical, human, and cultural aspects), but are only superficially discussed. This thesis builds a framework of the different approaches offered in literature. Furthermore, it is important to distinguish whether a new development as BDA can be seen as a trend topic or rather a long-lasting game changer for businesses. Here, this thesis discusses differences among digital capabilities, IT capabilities, that research stared addressing by 1990, and BDA capabilities. A major finding is that building IT capabilities is considered as an isolated responsibility of IT departments by, i.e., offering IT infrastructure to the whole company. BDA capabilities, on the contrary, cannot be planned and rolled out from one specific department – those need to be developed in every organizational unit; therefore, a data-driven culture is a key element in building BDA capabilities. Keywords: Big data analytics; Big data; Data analytics; Dynamic capabilities; Resource-based view.While the amount of data keeps growing, managers ask themselves whether they already retrieve full value from their data. To maximize the value of big data, literature offers first insights in building BDA capabilities (Gupta and George 2016, p; Mikalef et al. 2018). Nevertheless, BDA remains a new field to researchers and companies. BDA frameworks, still offered scarcely, discuss roughly the same dimensions (incorporating some technical, human, and cultural aspects), but are only superficially discussed. This thesis builds a framework of the different approaches offered in literature. Furthermore, it is important to distinguish whether a new development as BDA can be seen as a trend topic or rather a long-lasting game changer for businesses. Here, this thesis discusses differences among digital capabilities, IT capabilities, that research stared addressing by 1990, and BDA capabilities. A major finding is that building IT capabilities is considered as an isolated responsibility of IT departments by, i.e., offering IT infrastructure to the whole company. BDA capabilities, on the contrary, cannot be planned and rolled out from one specific department – those need to be developed in every organizational unit; therefore, a data-driven culture is a key element in building BDA capabilities. Keywords: Big data analytics; Big data; Data analytics; Dynamic capabilities; Resource-based view

NUMTs in Sequenced Eukaryotic Genomes

Mitochondrial DNA sequences are frequently transferred to the nucleus giving rise to the so-called nuclear mitochondrial DNA (NUMT). Analysis of 13 eukaryotic species with sequenced mitochondrial and nuclear genomes reveals a large interspecific variation of NUMT number and size. Copy number ranges from none or few copies in Anopheles, Caenorhabditis, Plasmodium, Drosophila, and Fugu to more than 500 in human, rice, and Arabidopsis. The average size is between 62 (baker’s yeast) and 647 bps (Neurospora), respectively. A correlation between the abundance of NUMTs and the size of the nuclear or the mitochondrial genomes, or of the nuclear gene density, is not evident. Other factors, such as the number and/or stability of mitochondria in the germline, or species-specific mechanisms controlling accumulation/loss of nuclear DNA, might be responsible for the interspecific diversity in NUMT accumulation

NUPTs in Sequenced Eukaryotes and Their Genomic Organization in Relation to NUMTs

NUPTs (nuclear plastid DNA) derive from plastid-to-nucleus DNA transfer and exist in various plant species. Experimental data imply that the DNA transfer is an ongoing, highly frequent process, but for the interspecific diversity of NUPTs, no clear explanation exists. Here, an inventory of NUPTs in the four sequenced plastid-bearing species and their genomic organization is presented. Large genomes with a predicted low gene density contain more NUPTs. In Chlamydomonas and Plasmodium, DNA transfer occurred but was limited, probably because of the presence of only one plastid per cell. In Arabidopsis and rice, NUPTs are frequently organized as clusters. Tight clusters can contain both NUPTs and NUMTs (nuclear mitochondrial DNA), indicating that preNUPTs and preNUMTs might have concatamerized before integration. The composition of such a hypothetical preNUPT-preNUMT pool seems to be variable, as implied by substantially different NUPTs:NUMTs ratios in different species. Loose clusters can span several dozens of kbps of nuclear DNA, and they contain markedly more NUPTs or NUMTs than expected from a random genomic distribution of nuclear organellar DNA. The level of sequence similarity between NUPTs/NUMTs and plastid/mitochondrial DNA correlates with the size of the integrant. This implies that original insertions are large and decay over evolutionary time into smaller fragments with diverging sequences. We suggest that tight and loose clusters represent intermediates of this decay process

Mode of Amplification and Reorganization of Resistance Genes During Recent Arabidopsis thaliana Evolution

The NBS-LRR (nucleotide-binding site plus leucine-rich repeat) genes represent the major class of disease resistance genes in flowering plants and comprise 166 genes in the ecotype Col-0 of Arabidopsis thaliana. NBS-LRR genes are organized in single-gene loci, clusters, and superclusters. Phylogenetic analysis reveals nine monophyletic clades and a few phylogenetic orphans. Most clusters contain only genes from the same phylogenetic lineage, reflecting their origin from the exchange of sequence blocks as a result of intralocus recombination. Multiple duplications increased the number of NBS-LRR genes in the progenitors of Arabidopsis, suggesting that the present complexity in Col-0 may derive from as few as 17 progenitors. The combination of physical and phylogenetic analyses of the NBS-LRR genes makes it possible to detect relatively recent gene rearrangements, which increased the number of NBS-LRR genes by about 50, but which are almost never associated with large segmental duplications. The identification of 10 heterogeneous clusters containing members from different clades demonstrates that sequence sampling between different resistance gene loci and clades has occurred. Such events may have taken place early during flowering plant evolution, but they generated modules that have been duplicated and remobilized also more recently

GignoMDA

Database Systems are often used as persistent layer for applications. This implies that database schemas are generated out of transient programming class descriptions. The basic idea of the MDA approach generalizes this principle by providing a framework to generate applications (and database schemas) for different programming platforms. Within our GignoMDA project [3]--which is subject of this demo proposal--we have extended classic concepts for code generation. That means, our approach provides a single point of truth describing all aspects of database applications (e.g. database schema, project documentation,...) with great potential for cross-layer optimization. These new cross-layer optimization hints are a novel way for the challenging global optimization issue of multi-tier database applications. The demo at VLDB comprises an in-depth explanation of our concepts and the prototypical implementation by directly demonstrating the modeling and the automatic generation of database applications

Funktion von CDC48 und Ubiquitin-bindenden Faktoren im proteasomalen Abbau

In eukaryontischen Zellen wird eine Vielzahl von Proteinen nach einer Modifikation mit Ubiquitin durch spezielle Substrat-Rezeptoren zum 26S Proteasom transportiert. Die AAA-ATPase CDC48, deren Kofaktoren und andere Ubiquitin-bindende Faktoren scheinen in diesen Prozess involviert zu sein. Die genaue Funktion von CDC48 und das Zusammenspiel der Faktoren in Degradationsprozessen sind jedoch nur unzureichend aufgeklärt. In dieser Arbeit konnte erstmals gezeigt werden, dass die Faktoren der Substrat- Rekrutierung, der Multiubiquitylierung und der Substratweitergabe zum Proteasom physikalisch interagieren und ein Netzwerk bilden, welches Substrate gezielt zum Proteasom leitet. CDC48 spielt in diesem Abbauweg eine zentrale Rolle, da es mit Hilfe der Kofaktoren UFD1/NPL4 in der Erkennung und Übertragung des Substrats auf das E4-Enzym UFD2 wirkt. Weiterhin wird durch CDC48 eine Termination der Ubiquitylierung erreicht, die einer exzessiven Bildung nicht-linearer Ubiquitinketten entgegenwirkt und so den Degradationsprozess optimiert. Die Multiubiquitylierung durch UFD2 ist über die Rezeptorproteine RAD23 und DSK2 mit dem Proteasom gekoppelt. Die Weiterleitung des Substrats zum Proteasom erfolgt in einem konzertierten Mechanismus, der über ternäre Komplexe aus RAD23, UFD2 und CDC48 bzw. durch Assoziation der beteiligten Ubiquitin-bindenden Faktoren am Proteasom erfolgt. Das in Gegenwart von CDC48 durch UFD2 ubiquitylierte Substrat kann über die UBA-Domänen der Rezeptoren RAD23 und DSK2 spezifisch gebunden und zum Proteasom übertragen werden. In vivo kontrolliert der dargestellte Abbauweg die Inaktivierung des Transkriptionsfaktors SPT23, welcher massgeblich über diesen UFD2-abhängigen Abbauweg degradiert wird. Zudem scheint SPT23 über einen parallelen Degradationsweg mittels des Proteins RPN10 abgebaut zu werden. Die Proteolyse von missgefalteten Proteinen des Endoplasmatischen Retikulums (ERAD) erfolgt ebenfalls über den hier dargestellten Abbauweg

Using Cloud Technologies to Optimize Data-Intensive Service Applications

The role of data analytics increases in several application domains to cope with the large amount of captured data. Generally, data analytics are data-intensive processes, whose efficient execution is a challenging task. Each process consists of a collection of related structured activities, where huge data sets have to be exchanged between several loosely coupled services. The implementation of such processes in a service-oriented environment offers some advantages, but the efficient realization of data flows is difficult. Therefore, we use this paper to propose a novel SOA-aware approach with a special focus on the data flow. The tight interaction of new cloud technologies with SOA technologies enables us to optimize the execution of data-intensive service applications by reducing the data exchange tasks to a minimum. Fundamentally, our core concept to optimize the data flows is found in data clouds. Moreover, we can exploit our approach to derive efficient process execution strategies regarding different optimization objectives for the data flows