Filtern
Volltext vorhanden
- nein (12) (entfernen)
Erscheinungsjahr
- 2021 (12) (entfernen)
Dokumenttyp
- Habilitation (12) (entfernen)
Gehört zur Bibliographie
- ja (12)
Schlagworte
- Arctic climate change (1)
- Christentum (1)
- Drought (1)
- FGF21 (1)
- Forecast (1)
- Frühmittelalter (1)
- GCN2 (1)
- Hydrological modeling (1)
- Monsoonal variability (1)
- North Atlantic climate change (1)
Institut
- Department Sport- und Gesundheitswissenschaften (2)
- Historisches Institut (2)
- Institut für Ernährungswissenschaft (2)
- Department Linguistik (1)
- Department Psychologie (1)
- Hochschulambulanz (1)
- Institut für Chemie (1)
- Institut für Geowissenschaften (1)
- Institut für Künste und Medien (1)
- Institut für Umweltwissenschaften und Geographie (1)
By using mouse outcross populations in combination with bioinformatic approaches, it was possible to identify and characterize novel genes regulating body weight, fat mass and β-cell function, which all contribute to the pathogenesis of obesity and T2D. In detail, the presented studies identified 1. Ifi202b/IFI16 as adipogenic gene involved in adipocyte commitment, maintenance of white adipocyte identity, fat cell size and the inflammatory state of adipose tissue. 2. Pla2g4a/PLA2G4A as gene linked to increased body weight and fat mass with a higher expression in adipose tissue of obese mice and pigs as well as in obese human subjects. 3. Ifgga2/IRGM as novel regulator of lipophagy protecting from excess hepatic lipid accumulation. 4. Nidd/DBA as a diabetogenic locus containing Kti12, Osbpl9, Ttc39a and Calr4 with differential expression in pancreatic islets and/or genetic variants. 5. miR-31 to be higher expressed in adipose tissue of obese and diabetic mice and humans targeting PPARy and GLUT4 and thereby involved in adipogenesis and insulin signaling. 6. Gjb4 as novel gene triggering the development of T2D by reducing insulin secretion, inducing apoptosis and inhibiting proliferation. The performed studies confirmed the complexity and strong genetic heritability character of obesity and T2D. A high number of genetic variations, each with a small effect, are collectively influencing the degree and severity of the disease. The use of mouse outcross populations is a valid tool for disease gene identification; however, to facilitate and accelerate the process of gene identification the combination of mouse cross data with advanced sequencing resources and the publicly available data sets are essential. The main goal for future studies should be the translation of these novel molecular discoveries to useful treatment therapies. More recently, several classes of novel unimolecular combination therapeutics have emerged with superior efficacy than currently prescribed options and pose the potential to reverse obesity and T2D (Finan et al., 2015). The glucagon-like peptide-1 (GLP-1)- estrogen conjugate, which targets estrogen into cells expressing GLP-1 receptors, was shown to improve energy, glucose and lipid metabolism as well as to reduce food reward (Finan et al., 2012; Schwenk et al., 2014; Vogel et al., 2016). Another possibility is the development of miRNA-based therapeutics to prevent obesity and T2D, such as miRNA mimetics, anti-miRNA oligonucleotides and exosomes loaded with miRNAs (Ji and Guo, 2019; Gottmann et al., 2020). As already described, genome-wide association studies for polygenic obesity and T2D traits in humans have also led to the identification of numerous gene variants with modest effect, most of them having an unknown function (Yazdi et al., 2015). These discoveries resulted in novel animal models and have illuminated new biologic pathways. Therefore, the integration of mouse-human genetic approaches and the utilization of the synergistic effects have the potential to lead to the identification of more genes responsible for common Mendelian forms of obesity and T2D, as well as gene × gene and gene × environment interactions (Yazdi et al., 2015; Ingelsson and McCarthy, 2018). This combination may help to unravel the missing heritability of obesity and T2D, to identify novel drug targets and to design more efficient and personalized obesity prevention and management programs.
Over millennia, droughts could not be understood or defined but rather were associated with mystical connotations. To understand this natural hazards, we first needed to understand the laws of physics and then develop plausible explanations of inner workings of the hydrological cycle. Consequently, modeling and predicting droughts was out of the scope of mankind until the end of the last century. In recent studies, it is estimated that this natural hazard has caused billions of dollars in losses since 1900 and that droughts have affected 2.2 billion people worldwide between 1950 and 2014.
For these reasons, droughts have been identified by the IPCC as the trigger of a web of impacts across many sectors leading to land degradation, migration and substantial socio-economic costs. This thesis summarizes a decade of research carried out at the Helmholtz Centre for Environmental Research on the subject of drought monitoring, modeling, and forecasting, from local to continental scales. The overarching objectives of this study, systematically addressed in the twelve previous chapters, are: 1) Create the capability to seamless monitor and predict water fluxes at various spatial resolutions and temporal scales varying from days to centuries; 2) Develop and test a modeling chain for monitoring, forecasting and predicting drought events and related characteristics at national and continental scales; and 3) Develop drought indices and impact indicators that are useful for end-users. Key outputs of this study are: the development of the open source model mHM, the German Drought Monitor System, the proof of concept for an European multi-model for improving water managent from local to continental scales, and the prototype of a crop-yield drought impact model for Germany.
Food intake is driven by the need for energy but also by the demand for essential nutrients such as protein. Whereas it was well known how diets high in protein mediate satiety, it remained unclear how diets low in protein induce appetite. Therefore, this thesis aims to contribute to the research area of the detection of restricted dietary protein and adaptive responses.
This thesis provides clear evidence that the liver-derived hormone fibroblast growth factor 21 (FGF21) is an endocrine signal of a dietary protein restriction, with the cellular amino acid sensor general control nonderepressible 2 (GCN2) kinase acting as an upstream regulator of FGF21 during protein restriction. In the brain, FGF21 is mediating the protein-restricted metabolic responses, e.g. increased energy expenditure, food intake, insulin sensitivity, and improved glucose homeostasis. Furthermore, endogenous FGF21 induced by dietary protein or methionine restriction is preventing the onset of type 2 diabetes in the New Zealand Obese mouse.
Overall, FGF21 plays an important role in the detection of protein restriction and macronutrient imbalance in rodents and humans, and mediates both the behavioral and metabolic responses to dietary protein restriction. This makes FGF21 a critical physiological signal of dietary protein restriction, highlighting the important but often overlooked impact of dietary protein on metabolism and eating behavior, independent of dietary energy content.
Bischöfe im Frankenreich waren einflussreiche politische Akteure, die im Laufe des 9. Jahrhunderts ein gelehrtes Wissen vom eigenen Amt entwickelten. Spiegelungen dieses Wissens über das Wesen des Bischofsamtes finden sich in vielen Texten, die meisten stammen aus Westfranken. Offen ist bislang jedoch, welche Relevanz dieses Wissen und das bischöfliche Standesbewusstsein hatten – ist es als normativer Referenzrahmen von anderen politisch relevanten Ständen anerkannt? Wie entwickelt es sich über die Umbruchzeit des 10. Jahrhunderts in der post-karolingischen Zeit und beginnenden Kirchenreform? Diesen Fragen widmet sich das Buch durch eine Untersuchung von Bischofsabsetzungen in Westfranken im 9. und 10. Jahrhundert und durch eine Analyse des Bischofsbildes in monastischen wie bischöflichen Kreisen im 10. und frühen 11. Jahrhundert. So kann ein differenziertes Bild der Wahrnehmung des Bischofsamtes und der konkrete Umgang mit dem Wissen vom Bischofsamt in verschiedenen Kontexten gezeichnet werden.
This habilitation thesis includes seven case studies that examine climate variability during the past 3.5 million years from different temporal and spatial perspectives. The main geographical focus is on the climatic events of the of the African and Asian monsoonal system, the North Atlantic as well as the Arctic Ocean. The results of this study are based on marine and terrestrial climate archives obtained by sedimentological and geochemical methods, and subsequently analyzed by various statistical methods.
The results herein presented results provide a picture of the climatic background conditions of past cold and warm periods, the sensitivity of past climatic climate phases in relation to changes in the atmospheric carbon dioxide content, and the tight linkage between the low and high latitude climate system. Based on the results, it is concluded that a warm background climate state strongly influenced and/or partially reversed the linear relationships between individual climate processes that are valid today. Also, the driving force of the low latitudes for climate variability of the high latitudes is emphasized in the present work, which is contrary to the conventional view that the global climate change of the past 3.5 million years was predominantly controlled by the high latitude climate variability. Furthermore, it is found that on long geologic time scales (>1000 years to millions of years), solar irradiance variability due to changes in the Earth-Sun-Moon System may have increased the sensitivity of low and high latitudes to Influenced changes in atmospheric carbon dioxide.
Taken together, these findings provide new insights into the sensitivity of past climate phases and provide new background conditions for numerical models, that predict future climate change.
Devotio malefica
(2021)
Antike Fluchrituale zielten darauf ab, die jeweilige Gerechtigkeitsvorstellung der Verfluchenden durchzusetzen – insbesondere wenn weder das öffentliche Justizsystem noch gesellschaftlich anerkannte Verhaltenskodize dem Anspruch gerecht werden konnten. In den Ritualen kamen sogenannte defixionis tabellae (Fluchtafeln) zur Anwendung, die hier devotiones maleficae genannt werden. Sie bestehen meistens aus eingeschriebenen Bleilamellen und wurden für die Beschädigung eines oder mehrerer Opfer angefertigt.
Sara Chiarini untersucht die dabei verwendete Fluchsprache, die durch ihre formelhaften Strukturen und Bestandteile auf eine Tradition des Fluchrituals hindeuten. Individuelle Ergänzungen bieten hingegen Hinweise auf die Bedingungen um die Entstehung des Rituals, die Gefühlslage der Verfluchenden und die Arten von Bestrafungen, die der rechtlichen Dimension des Rituals entsprechen. Chiarini ergänzt den bisherigen Forschungstand anhand der neu entdeckten und veröffentlichten Fluchtafeln und setzt sich umfassend mit diesem epigraphischen Material auseinander.