Newest publications
Regulation of fibroblast growth factor 23 (FGF23) in metabolic derangement
(2024) Alber, Jana; Föller, Michael
Increased incidence of metabolic syndrome is attributable to Western dietary patterns. Metabolic syndrome enhances risk of developing diabetes mellitus type 2 or cardiovascular diseases, which are associated with lactic acidosis, diabetic ketoacidosis and hyperhomocysteinemia. Increased lactate, ketone body or homocysteine levels are therefore relevant indicators of impaired metabolism and pathogenesis. FGF23 is an important regulator of calcitriol and phosphate homeostasis, and is predominantly synthesized in bone cells. Synthesis of FGF23 is regulated by various mechanisms including insulin/IGF1, mTOR, AMPK, PPARα, inflammation and oxidative stress. Increased FGF23 serum levels are correlated to inflammatory, renal and cardiovascular diseases, thus FGF23 represents an important therapeutic target and disease marker. Investigations unveiling regulation of FGF23 expression and synthesis as well as underlying mechanisms are therefore of high clinical significance. Hence, the present work aimed to elucidate a relevance of impaired metabolism on FGF23 formation, therefore establishing a basis for improved diagnosis as well as therapeutic approaches reducing morbidity and mortality in lactic acidosis, diabetic ketoacidosis or hyperhomocysteinemia. To this end, regulation of FGF23 synthesis under the influence of lactate, ketone bodies and homocysteine was analyzed. Lactic acid and sodium lactate enhanced Fgf23 expression in UMR106 osteoblast-like cells, an effect translated into higher cFGF23 concentration in cell culture supernatants. Application of NFκB inhibitors wogonin and withaferin A demonstrated an NFκB-mediated up-regulation of Fgf23 expression through lactic acid. Despite the knowledge that NFκB is an inducer of FGF23 formation and lactate stimulates NFκB activity, this study is the first to reveal a direct regulation of lactate on FGF23 production. As lactic acidosis is a common comorbidity in diabetes mellitus type 2 or cancer and increased lactate serum concentrations are associated with higher mortality, the findings of this study demonstrate FGF23 to be another useful biomarker for disease monitoring and prognosis. Furthermore homocysteine is a new regulator of FGF23 synthesis as shown within the present work, thus increasing Fgf23 expression and cFGF23 abundance in UMR106 cells. This effect is mediated by enhanced oxidative stress which stimulates FGF23 production, and is abolished by application of anti-oxidative ascorbic acid. Homocysteine serum levels are associated with versatile pathologies and its link to FGF23 signaling is therefore of clinical relevance, particularly in cardiovascular and renal diseases. In another investigation as part of this work, the ketone body βHB was identified as stimulator of FGF23 synthesis in UMR106 osteoblast-like cells as well as in primary cardiomyocytes, NRVM. Within NRVM, regulation of Fgf23 expression was shown to be dependent on MCT1/2 and HCAR2. Furthermore, intracellular activation of NFκB by βHB impacting on FGF23 synthesis was demonstrated in UMR106 cells. Moreover, short-term fasting (16 h) or βHB sodium salt administration increased FGF23 serum concentrations in C57BL/6 mice. These effects are of high relevance, since fasting-induced FGF23 synthesis was associated with lower NaPi-IIa and αklotho expression as well as with higher Cyp24a1 expression. In line with high FGF23 levels and enhanced Cyp24a1 expression, calcitriol serum levels of fasted animals were significantly lower compared to mice fed ad libitum. Other serum parameters including phosphate, calcium and PTH did not differ between both study groups. Further investigations revealed an important role of the heart as well as of thymus, spleen and pancreas in fasting-induced FGF23 synthesis. However, Fgf23 expression in bone and bone marrow did not differ between fasted mice and mice fed ad libitum, and was not detectable in liver tissue. As fasting and ketone body production are thought to be beneficial for various diseases and longevity, the findings of this investigation have enormous clinical implications. Since FGF23 has been demonstrated to be an important disease marker, and fasting induces FGF23 synthesis, blood samples of patients in fasting states may require careful interpretation. In conclusion, the present work is the first to demonstrate a direct regulation of FGF23 synthesis through lactate, ketone bodies and homocysteine. Hereby, NFκB signaling and generation of oxidative stress play a pivotal role. As FGF23 formation has been shown to be regulated through short-term fasting and to impact on phosphate homeostasis within the present work, the findings are highly implicated in physiology and pathophysiology. With respect to development of cardiovascular or renal diseases through lactic acidosis, diabetic ketoacidosis and homocysteinemia as well as to the relevance of FGF23 in these pathologies, the results of the present work are of significance for improved disease monitoring and establishment of new therapeutic approaches. Future investigations examining an involvement of metabolic regulators, e.g. insulin, mTOR, AMPK, PPARα, or of FGF co-receptor αklotho may provide further promising targets for therapy, diagnosis and prognosis of metabolic diseases.
Einfluss von klimatischen Faktoren auf das Quartiernutzungsverhalten des Großen Mausohrs (Myotis myotis) in Deutschland
(2024) Matthäus, Laura; Fietz, Joanna
Um dem dramatischen Artenrückgang der letzten Jahrzehnte entgegenzuwirken und die Folgen des Klimawandels einschätzen und seine Auswirkungen bewerten zu können, ist es unerlässlich, die Auswirkungen der klimatischen Veränderungen auf die Fauna zu beobachten. Nur auf dieser Grundlage können wirksame Maßnahmen zum Schutz der Arten ergriffen werden. Auch bei den Fledermäusen kam es ab Mitte der 1950er Jahre zu einem massiven Rückgang der Populationen mehrerer europäischer Fledermausar- ten. Bei einer dieser Arten handelt es sich um das Große Mausohr (Myotis myotis), für welches Deutschland aufgrund der weltweiten Verbreitung der Art sowie der Verteilung der Weltpopulation eine besondere Verantwortung trägt. Um auf Basis der FFH- Richtlinie, in deren Anhang II und Anhang IV das Große Mausohr geführt wird, dauerhaft einen wirksamen Schutz der Art in Deutschland gewährleisten zu können, war das Ziel der vorliegenden Dissertation, den Einfluss klimatischer Faktoren auf das Quartiernut- zungsverhalten des Großen Mausohrs zu untersuchen und ein Konzept für ein kontinu- ierliches bundesweites Monitoringsystem zu entwickeln. Es wird angenommen, dass die Änderungen klimatischer Faktoren Einfluss auf den Energieverbrauch sowie die Nahrungsverfügbarkeit und damit auf das Nahrungssuch- verhalten, die Reproduktion und das Überleben bzw. die Bestandsentwicklung von Fle- dermäusen haben. Um die Hypothese validieren zu können, wurde zunächst untersucht, welche Erfassungsmethoden geeignete Daten hierfür liefern können. Dazu wurden visu- elle Ausflugszählungen, halbautomatisierte Infrarotvideoaufnahmen und vollautomati- sierte Lichtschrankenerfassungen an Großen Mausohr-Wochenstuben synchron durch- geführt. Anhand des Methodenvergleichs sollen zudem die ehrenamtlichen und professionellen Kartierer, Wissenschaftler sowie Fachbehörden in der Auswahl einer geeigneten Erhe- bungsmethode unterstützt werden. Da der Vergleich der Datenqualität ergeben hat, dass diesbezüglich keine signifikanten Unterschiede zwischen den drei angewandten Metho- den vorliegen und auch die Anwesenheit des Kartierers keinen Einfluss im Sinne einer Störung auf den Ausflug der Großen Mausohren hat, kann die Wahl der geeigneten Er- fassungsmethode fallspezifisch von den Rahmenbedingungen und der Zielsetzung der Studie abhängig gemacht werden. Im Fall des angestrebten bundesweiten Großen Mausohr-Monitorings zur Überwachung des Großen Mausohrbestands in Deutschland im Rahmen der FFH-Richtlinie empfiehlt sich die Durchführung von permanenten Lichtschrankenerfassungen, um anhand von Langzeitaufnahmen mögliche Bestandsveränderungen in den Wochenstuben unmittel- bar identifizieren und geeignete Maßnahmen ergreifen zu können. Bei Bedarf kann die Lichtschrankenerfassung, beispielsweise zur Validierung, stichprobenartig mit anderen Methoden kombiniert werden. Somit konnte anhand der Untersuchung zum Methoden- vergleich die Eignung der Methode der Lichtschrankenerfassung und die Validität der erzeugten Daten für die Untersuchung von Klimaeinflüssen auf die Phänologie bestätigt werden. In der Folge wurden auf Basis von Lichtschrankenerfassungen gewonnene Daten her- angezogen, um das Quartiernutzungsverhalten des Großen Mausohrs in Abhängigkeit von klimatischen Faktoren zu analysieren. Hierfür wurde ermittelt, ob die Umgebungs- temperatur (Ta) einen Einfluss auf die Phänologie des Großen Mausohrs hat. Die vorliegenden Untersuchungen haben gezeigt, dass Veränderungen der Ta einen maßgeblichen Einfluss auf die Phänologie der Großen Mausohren haben. Dabei kann sich eine Erhöhung der Ta je nach Zeitpunkt positiv oder negativ auf die Fitness der Fledermäuse auswirken. So scheinen warme Winter bis zu einer gewissen Temperatur eine frühere Rückkehr in die Wochenstuben auszulösen, was je nach den anhaltenden Witterungsbedingungen und damit der Insektenverfügbarkeit positiv oder negativ für die Fledermäuse sein kann. Ein warmes Frühjahr wiederum scheint zu einem früheren Start der Geburten zu führen, wodurch ausreichende Energiereserven für den Winterschlaf angelegt werden können. Auch hohe Temperaturen während der Laktation der Fleder- mäuse sowie ein früherer Start der Geburten führten zu einer früheren Auflösung der Wochenstube, sodass die Überwinterung der Jung- und Muttertiere günstigen Bedingun- gen unterliegt, da bereits frühzeitig Energiereserven gesammelt werden können. Nach diesen Ergebnissen ist es unerlässlich, bei der Entwicklung von Maßnahmen zum Schutz der Fledermausfauna den Einfluss der klimatischen Veränderungen auf die Fle- dermäuse miteinzubeziehen. Die Erkenntnisse aus dem Methodenvergleich sowie die Ergebnisse der Untersuchung zum Einfluss der Umgebungstemperatur auf die Phänologie des Großen Mausohr wer- den in einem die Dissertation abschließenden Monitoringkonzept angewendet. Dieses Konzept ist auf den Fledermausschutz sowie insbesondere den Schutz in den Quartie- ren ausgerichtet und sieht eine permanente Aktivitätserfassung mittels Lichtschranken- Technik vor. Es konnte ein Monitoringdesign entwickelt werden, welches bei eintreten- den Verhaltensänderungen in Wochenstuben des Großen Mausohrs das unmittelbare Ergreifen von Maßnahmen ermöglicht, wodurch ein schneller und wirksamer Schutz der Art gewährleistet werden kann. Darüber hinaus werden die erforderlichen Bestandsda- ten generiert, um der auf der FFH-Richtlinie basierenden Berichtspflicht gegenüber der EU vollumfänglich nachkommen zu können.
Governance of responsible research and innovation: A social welfare, psychologically grounded multicriteria decision analysis approach
(2025) Paredes-Frigolett, Harold; Pyka, Andreas; Bevilacqua Leoneti, Alexandre; Nachar-Calderón, Pablo
Our article deals with the governance of responsible research and innovation (RRI) and aims to set out a first psychologically grounded decision-theoretic method for the governance of RRI. We approach the governance of RRI as a multicriteria group decision analysis problem of delivering social welfare in an innovation ecosystem. Following such a methodological approach, we develop a psychologically grounded multicriteria group decision analysis method that integrates in its value function the main psychological effects captured in the value function of prospect theory as the main theory of individual decision-making under risk. The method first applies a psychologically motivated multicriteria decision analysis function that measures the welfare delivered to all stakeholders involved in a research and innovation consortium. The method then applies a social welfare function on the welfare measurements of stakeholders to propose a social welfare solution that emerges as an RRI-compliant solution for the consortium. The results are a first psychologically grounded multicriteria group decision analysis method and its first application to the governance of RRI. The implications of our results are theoretical but also practical, as our method contributes not only to the established field of multicriteria decision analysis by setting out new method but also to the field of RRI by delivering a psychologically grounded decision-theoretic method for the governance of RRI.
Gender, sentiment, and market power: Essays on market inefficiencies
(2024) Braegelmann, Kylie Ann; Schiller, Jörg
This dissertation contributes to the literature on financial market inefficiencies. In Chapter 2, my co-author and I investigate a two-pronged regulation in the German private health insurance market, revealing the mixed effectiveness of measures aimed at decreasing insurers’ acquisition costs and increasing value of insurance for consumers in a market where brokers have market power. While the introduction of a minimum cancellation liability period appears effective, a commission cap shows limited success and unintended consequences for new business. In Chapter 3, my co-author and I provide an empirical test of social role theory, analyzing the relationship between gender equality and perception of income fairness in European countries. The results imply that higher gender equality is associated with individuals of all genders perceiving their income as fair, suggesting societal returns to gender equality; moreoever, the results also provide weak evidence that perception of income fairness converges with higher gender equality, which is in line with social role theory. In Chapter 4, my co-author and I explore gender bias in market reaction to CEO announcements, finding a negative reaction to female CEOs, with the bias diminishing over time and varying by firm size. In Chapter 5, I conduct sentiment analysis on new CEO announcements, showing an overall tendency for firms to use positive sentiment in new CEO announcements, and demonstrating that investors react to narrative sentiment, even in a setting where it is unverifiable. Overall, these studies enhance our understanding of market inefficiencies and their regulatory challenges, providing valuable insights for both academic research and practical implications in financial markets.
Is the system of rice intensification (SRI) pro poor? Labour, class and technological change in West Africa
(2021) Graf, Sarah Lena; Oya, Carlos
CONTEXT Increasing numbers of young people enter Sub-Saharan Africa's labour markets each year while industrial jobs only grow slowly. As 62% of Sub-Saharan Africans work in agriculture and as the rural population will continue to rise, agriculture will need to provide additional income- earning opportunities. In this context agricultural technologies should be promoted that can increase food production to answer rising demand and generate decent income-earning opportunities. The System of Rice Intensification (SRI) is widely promoted in West Africa and could address these needs – but recent findings from Asia present negative social impacts on workers. OBJECTIVE This paper explores the mechanisms that shape adoption patterns and impacts of SRI in different (West African) contexts through a labour lens. METHODS Our innovative theoretical framework integrates analytical and empirical categories from Farming Systems research and agrarian political economy. The mixed methods approach combines: (1) quantitative analysis of existing survey data from 857 agricultural households in Ghana, Benin and Mali; and (2) qualitative analysis of an in-depth case study in the Oti Region of Ghana. RESULTS AND CONCLUSION SRI increases yield and profitability in West African rice farming, especially when locally adapted. Farmers adjust SRI to fit lowland rice farming, where water cannot be controlled and to address labour constraints. Additional labour for transplanting (instead of broadcasting) – coinciding with an existing labour bottleneck – constrains SRI adoption. SRI is mainly practised by marginal and accumulating farmers and to a lesser extent by medium farmers. Accumulating farmers invest in agriculture, farm profit-oriented and overcome labour constraints by hiring. Thus, they can practise SRI on larger scale and their absolute benefits are higher. Nevertheless, they rely on hired labour to do so, which strengthens workers' bargaining position. Consequently, SRI benefits all: accumulating farmers who employ as well as marginal farmers and hired labourers. Contrary to findings from Asia, SRI seems to be relatively pro-poor in West Africa. SIGNIFICANCE While seasonal labour use remains a key constraint to technology adoption, labour intensive technologies can also contribute to increasing income-earning opportunities. The social outcomes of technological change will be shaped by both the existing agricultural practices and the social relations in which a new technology is adopted. Our theoretical framework can inform further research and the application of existing evidence to new contexts.