The functions of ICT1 and mtRbfA in the human mitochondrial ribosome

PhD ThesisDuring the last decades our knowledge about the human mitochondrial translation system has been expanded. However, our understanding of this unique system is far from complete. Mitochondria contain a minimal genome, whose expression is dependent on factors encoded by the nuclear genome. Derived from a bacterial ancestor it is very close to the translation system found in bacteria, but there are also a lot of differences especially the translating ribosome, which differs in a number of features including the sedimentation coefficient, protein-RNA ratio and number of tRNA sites. Available cryo-EM structures of the mitochondrial ribosome are limited, making it difficult to understand the system completely. There are still a lot of open questions concerning the composition, assembly, translation initiation or the recycling of stalled ribosomes in mammalian mitochondria. The study presented in this thesis contributes to our understanding of this unique system by the characterisation of two mitochondrial proteins, found in association with the mitochondrial ribosome, ICT1 and mtRbfA. These proteins are found in association with the mitochondrial ribosome, and were immunoprecipitated together with the mitochondrial ribosome recycling factor (mtRRF). ICT1 as a member of the mitochondrial release factor family has been identified as a peptidyl-tRNA hydrolase. Data shown here indicates that ICT1 has been recruited into the mitochondrial ribosome and further, suggests the involvement of ICT1 in the rescue of stalled ribosomal complexes with immobilised peptidyl-tRNA. In contrast mtRbfA was identified as a potential ribosome assembly factor rather than a permanent component. The function of this protein is still elusive, but data generated for this thesis shows that this protein is preferentially associated with the mitochondrial ribosomal small subunit at a late assembly point, suggesting possible roles of mtRbfA in quality control or in translation initiation

Virtual Currencies Like Bitcoin As A Paradigm Shift In The Field Of Transactions

Virtual currencies have been well-cited and well-discussed in the near past. Due to the loss of trust in the banking sector and the fear of loss of capital, low interest rates and uncertainty of existing currencies, the ground for a virtual currency was given. Virtual currencies and the money flows are controlled only online by the anonymous group of volunteers (also called peer); every single transaction is documented. Approximately 10,000 businesses worldwide accept payments with virtual currencies already, and the number is increasing steadily. This article analyzes the advantages and disadvantages of virtual currencies in comparison to real money and gives an outlook to a new banking system with high transparency and the chance to lead to a paradigm shift in the world of transactions and banking

Health Behavior and Associated Factors in Young Adult Cancer Patients

Objectives: Having cancer in young adulthood increases the risk of adverse long-term health effects. These risks can be influenced by one’s health behavior (HB). The aim of this study is therefore to investigate the presence of health behavior in adolescents and young adults (AYAs) and to identify associated factors. Design: Young cancer patients (18–39 years old at time of diagnosis) were surveyed at baseline and 12 months later via online or as a paper-pencil version. Methods: A spectrum of indicators for HB was assessed via seven items from the Questionnaire of Multiple Health Behavior (MHB). Multiple linear regression analyses were conducted to determine factors associated with patients’ HB indicators. Results: Five-hundred and fourteen AYAs (75% women) reported the highest level of health-conscious behavior for “avoidance of consumption of nicotine,” “follow medical recommendations,” and “being considerate in road traffic.” Less health-conscious behavior was reported for “keeping an appropriate and balanced diet” and “physical activity.” Significant improvements from baseline to the follow-up were observed for “regularly attending health screening” (Hedges’ g = 0.44). The analyzed factors explained up to 10% of the HB indicators. Women reported significantly more healthconscious behavior than men in four out of seven HB indicators. Higher quality of life (QoL) was associated with more health behavior in three out of seven HB indicators. Conclusion: Findings show a predominantly health-conscious lifestyle in AYA cancer patients, though we also found harmful behavior which needs to be better approached—e.g., through improving AYAs’ health education. AYA men should be particularly targeted in specific prevention and health promotion measures. Future work should identify other factors associated with HB to evaluate targets for intervention

Approaches to monitor and evaluate OER policies in higher education : tracing developments in Germany, Austria, and Switzerland

The 2019 UNESCO recommendation on Open Educational Resources (OER) encourages member states to monitor policies and mechanisms in OER across the world. In higher education, there are many initiatives and policies around OER. This contribution gives insights into the current situation concerning OER policy documents that are of national or institutional relevance for public higher education institutions in Germany, Switzerland, and Austria. For each country, a different approach for identifying OER policy documents was chosen, dependent on the availability of documents and different dominant forms of documentation. Whereas digital documents available on the web were found as helpful sources for Germany, and performance agreements between the national ministry and individual universities were used for analysis in Austria, a survey amongst all universities was the chosen research approach in Switzerland to give an overview about potentially OER related policy documents. All these documents are now made available via the OER World Map. With this contribution, the authors also highlight the possibility of using the OER World Map as a powerful tool to collect and evaluate OER policy documents

Approaches to monitor and evaluate OER policies in higher education : tracing developments in Germany, Austria, and Switzerland

The 2019 UNESCO recommendation on Open Educational Resources (OER) encourages member states to monitor policies and mechanisms in OER across the world. In higher education, there are many initiatives and policies around OER. This contribution gives insights into the current situation concerning OER policy documents that are of national or institutional relevance for public higher education institutions in Germany, Switzerland, and Austria. For each country, a different approach for identifying OER policy documents was chosen, dependent on the availability of documents and different dominant forms of documentation. Whereas digital documents available on the web were found as helpful sources for Germany, and performance agreements between the national ministry and individual universities were used for analysis in Austria, a survey amongst all universities was the chosen research approach in Switzerland to give an overview about potentially OER related policy documents. All these documents are now made available via the OER World Map. With this contribution, the authors also highlight the possibility of using the OER World Map as a powerful tool to collect and evaluate OER policy documents

A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome

Bioinformatic analysis classifies the human protein encoded by immature colon carcinoma transcript-1 (ICT1) as one of a family of four putative mitochondrial translation release factors. However, this has not been supported by any experimental evidence. As only a single member of this family, mtRF1a, is required to terminate the synthesis of all 13 mitochondrially encoded polypeptides, the true physiological function of ICT1 was unclear. Here, we report that ICT1 is an essential mitochondrial protein, but unlike the other family members that are matrix-soluble, ICT1 has become an integral component of the human mitoribosome. Release-factor assays show that although ICT1 has retained its ribosome-dependent PTH activity, this is codon-independent; consistent with its loss of both domains that promote codon recognition in class-I release factors. Mutation of the GGQ domain common to ribosome-dependent PTHs causes a loss of activity in vitro and, crucially, a loss of cell viability, in vivo. We suggest that ICT1 may be essential for hydrolysis of prematurely terminated peptidyl-tRNA moieties in stalled mitoribosomes

Role of GTPases in Driving Mitoribosome Assembly

Mitoribosomes catalyze essential protein synthesis within mitochondria. Mitoribosome biogenesis is assisted by an increasing number of assembly factors, among which guanosine triphosphate hydrolases (GTPases) are the most abundant class. Here, we review recent progress in our understanding of mitoribosome assembly GTPases. We describe their shared and specific features and mechanisms of action, compare them with their bacterial counterparts, and discuss their possible roles in the assembly of small or large mitoribosomal subunits and the formation of the monosome by establishing quality-control checkpoints during these processes. Furthermore, following the recent unification of the nomenclature for the mitoribosomal proteins, we also propose a unified nomenclature for mitoribosome assembly GTPases. Mitoribosome assembly involves at least six GTP hydrolases (GTPases) belonging to several conserved families.Mitoribosome assembly GTPases act to facilitate rRNA folding, and recruit mitoribosomal proteins and assembly factors to the assembly pathway.Maturation of the large mitoribosomal subunit (mtLSU) requires the assistance of several GTPases acting at late stages, when they function as antiassociation or quality-control factors to ensure joining of the mature small mitoribosomal subunit (mtSSU) and mtLSU into functional ribosomes.Impaired mitoribosome assembly GTPase function leads to defective mitochondrial protein synthesis and human disease.A novel unifying nomenclature for mitoribosome assembly GTPases is proposed

Parental feeding practices in families with children aged 2-13 years: Psychometric properties and child age-specific norms of the German version of the Child Feeding Questionnaire (CFQ)

The Child Feeding Questionnaire (CFQ) is a self-report questionnaire for assessing parental attitudes to child weight and parental feeding practices. revious evaluations of its psychometric properties were conducted primarily with small to medium-sized samples ( N < 500) and a small range of children's age. The present study aims to analyze the psychometric properties of the CFQ in a large German community sample and, for the first time, to establish normative data. Within the population-based LIFE Child study, the CFQ was administered to N - 982 mothers of 2- to 13-year-old children. Psychometric analyses on item statistics and internal consistency were conducted. Using structural equation modeling, four empirically-based factorial models of the CFQ were evaluated, and measurement invariance across child age groups and sex was examined. Age-specific norms for the CFQ subscales were computed. Item statistics were highly favorable for the majority of items, but floor and ceiling effects were found for 14 of 31 items. Internal consistency of the CFQ subscales ranged from acceptable to excellent (0.71< a < 0.91), except for the subscale Perceived Responsibility (a - 0.65). Regarding factorial validity, an eight-factor model with the newly created Reward subscale provided the best fit to the data. This model was factorial invariant across child sex and adjacent age groups. Maternal and child weight status showed large effects on CFQ subscale scores. The analyses established good psychometric properties for the German version of the CFQ and confirmed an eight-factor model. The provided norms allow for the comparison of individual parental feeding practices and change over time. The CFQ's sensitivity to change and longitudinal associations of parental feeding practices and child weight status warrant further research

Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HR-QoL) in Patients with Ovarian Cancer: What Is Different Compared to Healthy Women?

Simple Summary: The aim of this analysis was to evaluate the health-related quality of life (HR-QoL) in patients with ovarian cancer using a questionnaire based on patient-reported outcomes (PROs). The HR-QoL for 155 enrolled patients with ovarian cancer was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to surgery and compared with 501 healthy females in Germany, as well as to the previously published European Organization for Research and Treatment of Cancer (EORTC) reference data for 917 patients with ovarian cancer worldwide. The HR-QoL for the emotional, cognitive, and social functioning scales was lower in patients with ovarian cancer than the healthy female population. Interestingly, the patients with ovarian cancer had no significant differences in the physical functioning scale when compared with the healthy women. Furthermore, the younger patients with ovarian cancer had an even lower HR-QoL for the emotional, social, and cognitive functioning scales, and additionally had more fatigue and financial difficulties. Abstract: Introduction: The aim of this analysis was to evaluate the health-related quality of life (HR-QoL) in patients with ovarian cancer using a patient-reported outcome (PRO) based questionnaire and to compare it to the healthy female population in Germany and to other ovarian cancer patients worldwide. Additionally, we looked for differences in the HR-QoL with respect to the patients' ages in our cohort. Methods: The HR-QoL for 155 enrolled patients with ovarian cancer was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to surgery and then compared with 501 healthy females in Germany, as well as to the previously published European Organization for Research and Treatment of Cancer (EORTC) reference data for 917 patients with ovarian cancer worldwide. Moreover, we grouped our cohort by ages 65 years and analyzed them for further differences. To identify the differences, T-tests were applied. Results: Overall, 155 patients were enrolled, and 126 patients had advanced-stage ovarian cancer (FIGO III-IV) (82.4%). Fifty-five (36%) patients were >65 years. Except for the physical functioning scale, all other domains of the functioning scales were significantly lower in our patients with ovarian cancer than in the healthy female population. The emotional (50 points versus 60 points, p = 0.02), cognitive (76 points versus 88 points, p = 0.005), and social functioning scales (68 points versus 81 points, p = 0.006) were lower in the younger subgroup. Further, the younger subgroup exhibited significantly more fatigue (40 points versus 29 points, p = 0.03) and financial difficulties (20 points versus 2 points, p < 0.001) than the older subgroup. Discussion: Interestingly, the patients with ovarian cancer had no significant differences in the physical functioning scale when compared with the healthy women. In contrast, the patients, especially in the younger group, needed special support for the emotional and social areas of their daily lives