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Angesichts heutiger Umweltprobleme ist die Stärkung positiver Mensch-Natur-Beziehungen wichtiger denn je. Zeitgenössische Umweltbildung zielt darauf ab, Motivation und Einstellungen zu fördern sowie eine grundlegende Wissensbasis zu schaffen (IUCN, UNEP, & WWF, 1991; Potter, 2010), um einen selbstbestimmten, verantwortungsvollen Umgang mit der Natur zu ermöglichen. Positiver Naturbezug und Umwelteinstellungen gelten als Basis für aktiven Umweltschutz. Direkte Naturerfahrungen gelten dabei als didaktische Möglichkeit, die Motivation für Umweltschutz zu festigen (Kaiser, Roczen, & Bogner, 2008). Einstellungen verändern sich im Laufe des Lebens und so kann das Alter eine wichtige Rolle bezüglich der Effektivität von Umweltbildungsprogrammen spielen (Ernst & Theimer, 2011). Auch Umweltwissen gilt als Grundlage von Umwelthandeln. Denn sinnliche Erfahrungen allein führen nicht zum Verständnis ökologischer Zusammenhänge (Frick, Kaiser, & Wilson, 2004; Liefländer, Bogner, Kibbe, & Kaiser, 2015). Die biologiedidaktische Forschung sieht Fakten-, Handlungs- und Effektivitäts-wissen als zentral für die Genese von Umwelthandeln (Frick, Kaiser, & Wilson, 2004). Isoliertes Fachwissen wiederum führt nach aktueller Erkenntnis auch nicht zur Entwicklung von Haltungen und Wertvorstellungen, welche unser Handeln beeinflussen (Barr, 2003; Finger, 2010; Leiserowitz, Kates, & Parris, 2005).
Bis heute sind altersbasierte Unterschiede bei Schülerinnen und Schülern bezüglich ihrer Naturverbundenheit und Umwelteinstellungen nicht hinreichend untersucht. Auch ist die nötige Dauer der Naturerfahrungen noch nicht nachgewiesen. Es gibt bislang keine Studie, die Umwelteinstellungen, -wissen und –handeln von Kindern verschiedener Regionen der Erde untersucht und Daten auf internationaler Ebene erhoben und ausgewertet hat. Die gezielte Integration der drei Umweltwissensarten in ein solch globales Umweltbildungsprojekt stellt eine zusätzliche bislang nicht angegangene Aufgabe dar. Die vorliegende Arbeit schließt diese Forschungslücken, indem sie auf internationaler Ebene jene Variablen mit einbezieht, die einen nahezu vollständigen Eindruck der Effektivität von Umweltbildung in verschiedenen Regionen, Sozialisationen und Altersklassen zulässt. So wird der Einfluss eines umfassenden Umweltbildungsprogramms auf Naturverbundenheit, Umwelteinstellungen und -wissen der verschiedenen Typen untersucht und ein Bezug zur eventuellen Veränderung des Umwelthandelns hergestellt. Dabei stehen sowohl traditionelle als noch unerforschte mögliche Einflussfaktoren im Fokus. Die Studie umfasst insgesamt 1454 Schülerinnen und Schüler aus Bangladesch, Malaysia, Deutschland und Singapur, die alle an dem Umweltbildungsprojekt „Global denken, lokal handeln – wir schützen unsere Umwelt!“ bzw. “Think global, act local – we protect our environment!“ teilgenommen haben.
Zur Messung der Naturverbundenheit diente Schulz’ INS-Skala (Inclusion of Nature in Self) (2002). Umwelteinstellungen wurden mit dem 2-MEV-Modell (Two Major Environmental Values) gemessen (Johnson & Manoli, 2011). Eine Skala zur Erhebung von Umweltwissen wurde eigens erstellt und hinsichtlich der drei Wissenstypen nochmals modelliert. Eine Skala zur Ermittlung von Umwelthandeln wurde auf Grundlage von Bögeholz (1999) erstellt. Alle Skalen waren Teil eines Fragebogens, welcher in Form eines Pre-, Post- und Follow-up-Test eingesetzt wurde. Kinder aus Parallelklassen, die nicht am Projekt teilnahmen, aber Klassenunterricht zu den jeweiligen Themen erhielten, dienten als Kontrollgruppen.
Die Ergebnisse bestätigen einen positiven Effekt außerschulischer Umweltbildung bezüglich der Entwicklung der untersuchten Variablen. So wurde nach der Teilnahme am eintägigen und auch nach dem fünftägigen Umweltbildungsprogramm eine signifikante Verstärkung des Naturbezugs gemessen, wohingegen die Kontrollgruppen keine messbare Veränderung zeigten. Jedoch nur die fünftägige Intervention führte auch zu nachhaltigen Veränderungen. Hierbei am stärksten beeinflusst wurden Kinder zwischen sieben und neun Jahren.
Bei der Untersuchung demographischer Einflussfaktoren auf Umwelteinstellung, -wissen und –handeln stellten sich das Wohnsitzland sowie die städtische bzw. ländliche Prägung der Wohngegend als entscheidend heraus. So waren dies die einflussreichsten Determinanten zur Vorhersage des Grundvorhandenseins sowie Veränderungen der untersuchten Variablen in Folge der Bildungsmaßnahme. Einzig bei der Entwicklung des Umwelthandelns schien die direkte Naturerfahrung unwesentlich, zeigten die Kontrollgruppen ähnlichen Wandel in ihrem aktiven Einsatz für die Umwelt. Im internationalen Vergleich scheint die komplexe Verkettung diverser einflussnehmender Faktoren, wie der Wohlstand des jeweiligen Staates, das generelle politische System sowie spezifische bildungspolitische Begebenheiten, den Erfolg von Umweltbildungsprogrammen mit zu bestimmen.
Die Daten zeigen, dass Faktenwissen Grundlage für Handlungs- und Effektivitätswissen ist. Alle Dimensionen wurden durch die Intervention signifikant gesteigert. Effektivitätswissen wuchs am stärksten. Auch das Umweltverhalten wurde positiv verstärkt. Jedoch ließen sich nur schwache Korrelationen zwischen den einzelnen Wissenstypen und Handeln feststellen. Zusammenfassend war das durchgeführte Bildungsprojekt erfolgreich in der Förderung von Naturverbundenheit sowie Umwelteinstellungen, -wissen und- handeln. Die Ergebnisse werden im Rahmen dieser Arbeit im Hinblick auf ihre Bedeutung für die schulische Umweltbildung sowie die didaktische Forschung erörtert.
A major driving force for the adaptation of bacteria to changing environments is the uptake of naked DNA from the environment by natural transformation, which allows the acquisition of new capabilities. Uptake of the high molecular weight DNA is mediated by a complex transport machinery that spans the entire cell periphery. This DNA translocator catalyzes the binding and splitting of double‐stranded DNA and translocation of single‐stranded DNA into the cytoplasm, where it is recombined with the chromosome. The thermophilic bacterium Thermus thermophilus exhibits the highest transformation frequencies reported and is a model system to analyze the structure and function of this macromolecular transport machinery. Transport activity is powered by the traffic ATPase PilF, a soluble protein that forms hexameric complexes. Here, we demonstrate that PilF physically binds to an inner membrane assembly platform of the DNA translocator, comprising PilMNO, via the ATP‐binding protein PilM. Binding to PilMNO or PilMN stimulates the ATPase activity of PilF ~ 2‐fold, whereas there is no stimulation when binding to PilM or PilN alone. A PilMK26A variant defective in ATP binding still binds PilF and, together with PilN, stimulates PilF‐mediated ATPase activity. PilF is unique in having three conserved GSPII (general secretory pathway II) domains (A–C) at its N terminus. Deletion analyses revealed that none of the GSPII domains is essential for binding PilMN, but GSPIIC is essential for PilMN‐mediated stimulation of ATP hydrolysis by PilF. Our data suggest that PilM is a coupling protein that physically and functionally connects the soluble motor ATPase PilF to the DNA translocator via the PilMNO assembly platform.
Bakterien sind wahre Überlebenskünstler. Im Laufe der Evolution haben sie zahlreiche Strategien entwickelt, sich an schnell veränderliche, unsichere Umweltbedingungen anzupassen. So ist ihr Stoffwechsel wesentlich ausgeklügelter als derjenige des Menschen. Sie können innerhalb von Minuten ihre Genexpression anpassen und zur Not auch jahrzehntelang in Sporenform auf bessere Zeiten warten.
Several peptides in clinical use are derived from non-ribosomal peptide synthetases (NRPS). In these systems multiple NRPS subunits interact with each other in a specific linear order mediated by specific docking domains (DDs), whose structures are not known yet, to synthesize well-defined peptide products. In contrast to classical NRPSs, single-module NRPS subunits responsible for the generation of rhabdopeptide/xenortide-like peptides (RXPs) can act in different order depending on subunit stoichiometry thereby producing peptide libraries. To define the basis for their unusual interaction patterns, we determine the structures of all N-terminal DDs (NDDs) as well as of an NDD-CDD complex and characterize all putative DD interactions thermodynamically for such a system. Key amino acid residues for DD interactions are identified that upon their exchange change the DD affinity and result in predictable changes in peptide production. Recognition rules for DD interactions are identified that also operate in other megasynthase complexes.
During erythropoiesis, haematopoietic stem cells (HSCs) differentiate in successive steps of commitment and specification to mature erythrocytes. This differentiation process is controlled by transcription factors that establish stage- and cell type-specific gene expression. In this study, we demonstrate that FUSE binding protein 1 (FUBP1), a transcriptional regulator important for HSC self-renewal and survival, is regulated by T-cell acute lymphocytic leukaemia 1 (TAL1) in erythroid progenitor cells. TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation. The binding of TAL1 to the FUBP1 promoter is highly dependent on an intact GATA sequence in a combined E-box/GATA motif. We found that FUBP1 expression is required for efficient erythropoiesis, as FUBP1-deficient progenitor cells were limited in their potential of erythroid differentiation. Thus, the finding of an interconnection between GATA1/TAL1 and FUBP1 reveals a molecular mechanism that is part of the switch from progenitor- to erythrocyte-specific gene expression. In summary, we identified a TAL1/FUBP1 transcriptional relationship, whose physiological function in haematopoiesis is connected to proper erythropoiesis.
Biosynthetic gene content of the "Perfume Lichens" Evernia prunastri and Pseudevernia furfuracea
(2019)
Lichen-forming fungi produce a vast number of unique natural products with a wide variety of biological activities and human uses. Although lichens have remarkable potential in natural product research and industry, the molecular mechanisms underlying the biosynthesis of lichen metabolites are poorly understood. Here we use genome mining and comparative genomics to assess biosynthetic gene clusters and their putative regulators in the genomes of two lichen-forming fungi, which have substantial commercial value in the perfume industry, Evernia prunastri and Pseudevernia furfuracea. We report a total of 80 biosynthetic gene clusters (polyketide synthases (PKS), non-ribosomal peptide synthetases and terpene synthases) in E. prunastri and 51 in P. furfuracea. We present an in-depth comparison of 11 clusters, which show high homology between the two species. A ketosynthase (KS) phylogeny shows that biosynthetic gene clusters from E. prunastri and P. furfuracea are widespread across the Fungi. The phylogeny includes 15 genomes of lichenized fungi and all fungal PKSs with known functions from the MIBiG database. Phylogenetically closely related KS domains predict not only similar PKS architecture but also similar cluster architecture. Our study highlights the untapped biosynthetic richness of lichen-forming fungi, provides new insights into lichen biosynthetic pathways and facilitates heterologous expression of lichen biosynthetic gene clusters.
Neuropogonoid species in the lichen-forming fungal genus Usnea exhibit great morphological variation that can be misleading for delimitation of species. We specifically focused on the species delimitation of two closely-related, predominantly Antarctic species differing in the reproductive mode and representing a so-called species pair: the asexual U. antarctica and the sexual U. aurantiacoatra. Previous studies have revealed contradicting results. While multi-locus studies based on DNA sequence data provided evidence that these two taxa might be conspecific, microsatellite data suggested they represent distinct lineages. By using RADseq, we generated thousands of homologous markers to build a robust phylogeny of the two species. Furthermore, we successfully implemented these data in fine-scale population genomic analyses such as DAPC and fineRADstructure. Both Usnea species are readily delimited in phylogenetic inferences and, therefore, the hypothesis that both species are conspecific was rejected. Population genomic analyses also strongly confirmed separated genomes and, additionally, showed different levels of co-ancestry and substructure within each species. Lower co-ancestry in the asexual U. antarctica than in the sexual U. aurantiacoatra may be derived from a wider distributional range of the former species. Our results demonstrate the utility of this RADseq method in tracing population dynamics of lichens in future analyses.
Startle disease or hereditary hyperekplexia has been shown to result from mutations in the α1‐subunit gene of the inhibitory glycine receptor (GlyR). In hyperekplexia patients, neuromotor symptoms generally become apparent at birth, improve with age, and often disappear in adulthood. Loss‐of‐function mutations of GlyR α or β‐subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR β transgene into the spastic mouse (spa/spa), a recessive mutant carrying a transposon insertion within the GlyR β‐subunit gene. In spa/spa TG456 mice, one of three strains generated with this construct, which expressed very low levels of GlyR β transgene‐dependent mRNA and protein, the spastic phenotype was found to depend upon the transgene copy number. Notably, mice carrying two copies of the transgene showed an age‐dependent sensitivity to tremor induction, which peaked at ∼ 3–4 weeks postnatally. This closely resembles the development of symptoms in human hyperekplexia patients, where motor coordination significantly improves after adolescence. The spa/spa TG456 line thus may serve as an animal model of human startle disease.
Colorectal cancer (CRC) has the third highest incidence and the fourth highest mortality rate worldwide and represents a substantial health care burden and affects the life of millions of people. CRC is a genetic disease caused by the stepwise accumulation of genetic alterations. The initiating event in colorectal carcinogenesis is the aberrant activation of the WNT pathway, but other pathways are also commonly deregulated, including the PI3K/AKT pathway. A number of previous studies using genetically engineered mouse models aimed at dissecting the exact role of PI3K/AKT pathway in CRC, but have yielded in rather conflicting results. Despite the inconsistent results, these studies already put forward the idea that PI3K/AKT signaling in combination with other genetic events might substantially contribute to tumor progression. Since the PI3K/AKT pathway is frequently activated in CRC, it represents an ideal candidate for therapeutic intervention. Although extensive efforts had led to the development of numerous inhibitors targeting the PI3K/AKT pathway, the diversity of genetic alterations can challenge the identification of the most effective therapeutic targets. Therefore, the discovery of shared tumor-promoting mechanisms downstream of these genetic alterations might unravel new biomarkers and druggable targets. The aim of this study was to elucidate the precise role of PI3K/AKT pathway during the course of colorectal carcinogenesis and to decipher novel protumorigenic molecular mechanisms downstream of PI3K/AKT activation that can be used for therapeutic intervention.
To obtain a better insight into the role of the PI3K/AKT pathway during colorectal carcinogenesis, mice expressing an oncogenic variant of AKT1 (AktE17K) specifically in the intestinal epithelial cells (IEC) were used. At the age of 6 months untreated AktE17K mice showed clearly perturbed intestinal homeostasis, but no tumor formation. To induce colonic tumorigenesis, AktE17K mice were subjected to treatment with the colonic carcinogen azoxymethane (AOM). In response to AOM, AktE17K mice developed invasive but non-metastatic tumors, which showed strong nuclear accumulation of TP53. To investigate the role of PI3K/AKT signaling specifically in CRC progression, AktE17K mice were crossed to TP53-deficient mice (Tp53ΔIEC). Unlike AktE17K mice, untreated Tp53ΔIEC; AktE17K, developed highly invasive small
intestinal tumors by the age of 6 months. To investigate the role of AKT hyperactivation in colonic tumor progression, Tp53ΔIEC; AktE17K mice were subjected to AOM treatment. AKT hyperactivation significantly enhanced tumor progression and induced metastatic dissemination.
To get a better insight how AKT signaling can promote tumor progression, whole tumor tissues from AOM-treated Tp53ΔIEC and Tp53ΔIEC; AktE17K mice were subjected to next generation mRNA sequencing and phospho-proteomic analysis by mass spectrometry. Both analyses indicated that AKT hyperactivation expands the inflammatory tumor microenvironment and upregulates pathways associated with invasion and metastasis. Importantly, Gene Set Enrichment Analysis revealed that AOM-induced colon tumors of Tp53ΔIEC; AktE17K animals, are highly similar in their gene expression profile to the CMS4 subtype of human CRC, which is associated with worse overall- and relapse-free survival. Gene expression analysis also suggested elevated NOTCH signaling in the Tp53ΔIEC; AktE17K tumors. Interestingly, while the expression of Notch3 mRNA was increased in the tumors of Tp53ΔIEC; AktE17K mice, the expression of the other NOTCH receptors was unaffected by AKT hyperactivation. In vitro experiments using TP53-deficient mouse tumor organoids with hyperactive AKT signaling confirmed the direct, tumor cell-intrinsic link between AKT activation and increased Notch3 expression. Moreover, inhibition of EZH2 mimicked the effect of AKT hyperactivation on Notch3 expression, suggesting that AKT regulates Notch3 via an epigenetic mechanism.
Knock-down of Notch3 in TP53-deficient mouse tumor organoids with hyperactive AKT signaling resulted in differential regulation of several pathways with potential role in invasion and metastasis and in cell death and survival. Subsequent in vivo experiments confirmed the role of NOTCH3 signaling in CRC progression. Treatment of AOM-induced Tp53ΔIEC; AktE17K mice with a NOTCH3 antagonistic antibody or the γ-secretase inhibitor DAPT significantly reduced invasion and metastasis. Importantly, NOTCH3 expression was also found to be associated with human CRC progression, suggesting that NOTCH3 represent a valid target for the treatment of CRC. This work, using genetically engineered mouse models and advanced in vitro techniques, has demonstrated a strong tumor promoting role for PI3K/AKT signaling in CRC progression and has identified NOTCH3 signaling as a potential therapeutic target downstream of the PI3K/AKT pathway.