Refine
Has Fulltext
- no (1413) (remove)
Year of publication
Document Type
- Doctoral Thesis (1413) (remove)
Language
- English (1413) (remove)
Keywords
- photosynthesis (5)
- Arabidopsis thaliana (4)
- Klimawandel (3)
- Photosynthese (3)
- Wissensmanagement (3)
- climate change (3)
- fluctuating light (3)
- metabolism (3)
- metabolomics (3)
- plant (3)
Institute
- Institut für Biochemie und Biologie (472)
- Institut für Physik und Astronomie (201)
- Institut für Chemie (154)
- Institut für Geowissenschaften (107)
- Institut für Ernährungswissenschaft (75)
- Institut für Mathematik (67)
- Institut für Informatik und Computational Science (64)
- Wirtschaftswissenschaften (42)
- Department Linguistik (33)
- Institut für Umweltwissenschaften und Geographie (33)
Functional characterization of ROS-responsive genes, ANAC085 and ATR7, in Arabidopsis thaliana
(2023)
Diabetes is a major public health problem with increasing global prevalence. Type 2 diabetes (T2D), which accounts for 90% of all diagnosed cases, is a complex polygenic disease also modulated by epigenetics and lifestyle factors. For the identification of T2D-associated genes, linkage analyses combined with mouse breeding strategies and bioinformatic tools were useful in the past. In a previous study in which a backcross population of the lean and diabetes-prone dilute brown non-agouti (DBA) mouse and the obese and diabetes-susceptible New Zealand obese (NZO) mouse was characterized, a major diabetes quantitative trait locus (QTL) was identified on chromosome 4. The locus was designated non-insulin dependent diabetes from DBA (Nidd/DBA). The aim of this thesis was (i) to perform a detailed phenotypic characterization of the Nidd/DBA mice, (ii) to further narrow the critical region and (iii) to identify the responsible genetic variant(s) of the Nidd/DBA locus. The phenotypic characterization of recombinant congenic mice carrying a 13.6 Mbp Nidd/DBA fragment with 284 genes presented a gradually worsening metabolic phenotype. Nidd/DBA allele carriers exhibited severe hyperglycemia (~19.9 mM) and impaired glucose clearance at 12 weeks of age. Ex vivo perifusion experiments with islets of 13-week-old congenic mice revealed a tendency towards reduced insulin secretion in homozygous DBA mice. In addition, 16-week-old mice showed a severe loss of β-cells and reduced pancreatic insulin content. Pathway analysis of transcriptome data from islets of congenic mice pointed towards a downregulation of cell survival genes. Morphological analysis of pancreatic sections displayed a reduced number of bi-hormonal cells co-expressing glucagon and insulin in homozygous DBA mice, which could indicate a reduced plasticity of endocrine cells in response to hyperglycemic stress. Further generation and phenotyping of recombinant congenic mice enabled the isolation of a 3.3 Mbp fragment that was still able to induce hyperglycemia and contained 61 genes. Bioinformatic analyses including haplotype mapping, sequence and transcriptome analysis were integrated in order to further reduce the number of candidate genes and to identify the presumable causative gene variant. Four putative candidate genes (Ttc39a, Kti12, Osbpl9, Calr4) were defined, which were either differentially expressed or carried a sequence variant. In addition, in silico ChIP-Seq analyses of the 3.3 Mbp region indicated a high number of SNPs located in active regions of binding sites of β-cell transcription factors. This points towards potentially altered cis-regulatory elements that could be responsible for the phenotype conferred by the Nidd/DBA locus. In summary, the Nidd/DBA locus mediates impaired glucose homeostasis and reduced insulin secretion capacity which finally leads to β-cell death. The downregulation of cell survival genes and reduced plasticity of endocrine cells could further contribute to the β-cell loss. The critical region was narrowed down to a 3.3 Mbp fragment containing 61 genes, of which four might be involved in the development of the diabetogenic Nidd/DBA phenotype.
This book endeavours to understand the seemingly direct link between utopianism and the USA, discussing novels that have never been brought together in this combination before, even though they all revolve around intentional communities: Imlay’s The Emigrants (1793), Hawthorne’s The Blithedale Romance (1852), Howland’s Papas Own Girl (1874), Griggs’s Imperium in Imperio (1899), and Du Bois’s The Quest of the Silver Fleece (1911). They relate nation and utopia not by describing perfect societies, but by writing about attempts to immediately live radically different lives. Signposting the respective communal history, the readings provide a literary perspective to communal studies, and add to a deeply necessary historicization for strictly literary approaches to US utopianism, and for studies that focus on Pilgrims/Puritans/Founding Fathers as utopian practitioners. This book therefore highlights how the authors evaluated the USA’s utopian potential and traces the nineteenth-century development of the utopian imagination from various perspectives.