Die Rolle antimikrobieller Peptide in der COPD: Expressionsmuster und möglicheRegulationsmechanismen in der Lungevon Patienten mit chronisch obstruktiver Lungenerkrankung

Die chronisch obstruktive Lungenerkrankung (COPD, chronic obstructive pulmonary disease) ist eine Volkskrankheit. Bisher ist jedoch unklar, inwieweit und durch welche Parameter der Verlust der Lungenfunktion, welcher das wesentliche klinische Merkmal der COPD darstellt, determiniert ist. Genomweite Kopplungsstudien haben hierfür relevante Regionen mit einer Kopplung auf dem Chromosom 8p identifiziert, in der die humanen Defensin-Gene innerhalb eines Gen-Clusters vorliegen. Für das Gen des humanen Defensin, beta 1 (DEFB1) konnte ein Allel mit einer signifikanten Assoziation zur COPD nachgewiesen werden. Die Bedeutung von DEFB1 und seine klinische Relevanz für die vielfältigen Phänomene der COPD-Pathogenese wurden bisher jedoch nicht eingehend untersucht. Die Ergebnisse der vorliegenden Arbeit zeigen, dass die COPD mit einer gesteigerten Expression von DEFB1 in der Lunge einhergeht. Des Weiteren wurde eine signifikante Korrelation der DEFB1-Expression in Bronchialschleimhautbiopsien mit allen relevanten Parametern der COPD-Diagnostik einschließlich der allgemeinen Leistungsfähigkeit der Patienten wie 6-Min-Gehtest, Zigarettenkonsum und Lungenfunktionstests nachgewiesen. Da diese Parameter Informationen über die Prognose einer COPD liefern, stellt die DEFB1-Expression auch einen potentiellen prognostischen Marker für das Fortschreiten dieser Erkrankung dar. Im Rahmen dieser Arbeit wurde nach Mechanismen gesucht, die an der Regulation von DEFB1 in der Lunge von COPD-Patienten beteiligt sind. Dabei zeigte sich, dass eine Störung der epigenetischen Regulationsvorgänge bei der Pathogenese der COPD eine Rolle spielen könnte. Während kein Zusammenhang zwischen der CpG-Methylierung im DEFB1-Gen und dessen Expression im Biopsiematerial von COPD-Patienten festgestellt werden konnte, zeigte eine allgemeine Inhibierung der DNA-Methylierung durch 5-Aza-2'-Desoxycytidin im Zellkulturmodell hingegen einen starken Einfluss auf die DEFB1-Expression. Durch Verwendung des Histon-Deacetylase-Inhibitors Trichostatin A konnte gezeigt werden, dass die Acetylierung bei der transkriptionellen Aktivierung von DEFB1 ebenfalls eine Rolle spielt. Chromatinimmunpräzipitations-Analysen mit Zellen der bronchoalveolären Lavage-Flüssigkeit zeigten eine signifikante Korrelation zwischen der DEFB1-Expression und dem Aufbau eines aktiven "Histon-Codes" und deuten ebenfalls auf eine wichtige Rolle von kovalenten Histon-Modifikationen im DEFB1 und damit der epigenetischen Regulation bei der COPD hin. Insgesamt bekräftigen diese Daten die Hypothese, dass DEFB1 in die molekulare Maschinerie der COPD-Pathogenese eingebunden ist. Die ersten Einblicke in die epigenetischen Kontroll-Mechanismen der DEFB1-Regulation liefern neue Erkenntnisse über funktionelle Zusammenhänge, die auf ein besseres Verständnis der komplexen Pathomechanismen der COPD hoffen lassen und somit zur Entwicklung neuer innovativer Therapien beitragen könnten.Chronic obstructive pulmonary disease (COPD) is a widespread disease. However, the key factors determining the decline in lung function, which is the most important clinical parameter of COPD, are not yet clear. Genome-wide linkage analyses provide evidence for significant linkage to airway obstruction susceptibility loci on chromosome 8p, the location of the human defensin gene cluster. Moreover, a genetic variation in the human defensin, beta 1 (DEFB1) gene was found to be associated with COPD. However, the role of DEFB1 and its clinical relevance in diverse phenomena of COPD pathogenesis has not been extensively studied so far. The results of this dissertation demonstrate a significant increase of DEFB1 expression in the lung of COPD patients. Furthermore, a significant correlation could be detected between DEFB1 gene expression in biopsies of the bronchial mucosa and the relevant diagnostic parameter for COPD including exercise capacity as measured by the six-minute-walk test, cigarette smoking and lung function tests. Since these parameters are used to predict the outcome of COPD, DEFB1 gene expression may thus be considered as a new potential predictive marker for the outcome of COPD patients. Mechanisms involved in the regulation of DEFB1 gene expression in the lung of COPD patients were also studied, showing that a dysfunction of the epigenetic regulation could play a role in the pathogenesis of COPD. Whereas bisulfite sequencing analysis of the bronchial mucosa revealed no differences in the methylation state of DEFB1 between COPD patients and healthy controls, an inhibition of DNA methylation by 5-aza-2'-deoxycytidine in cell lines resulted in a remarkable induction of DEFB1 gene expression. Additionally, treatment of the cells with the deacetylases inhibitor trichostatin A revealed a role for acetylation in the transcriptional activation of DEFB1. Finally, chromatin immunoprecipitation assays with bronchoalveolar lavage fluid cells showed that DEFB1 activation was associated with the establishment of an active "histone code" suggesting the important role of covalent histone modifications in the regulation of DEFB1 expression. In conclusion, these data support the hypothesis that DEFB1 is associated with pathological changes characteristic for COPD. The first insight into epigenetic control mechanisms of DEFB1 regulation provides new knowledge about their functional contexts, which hopefully will lead to a better understanding of the complex pathomechanisms of COPD and thus may contribute to developing new innovative therapies

Respect and tolerance.

Bacheloroppgave, grunnskolelærerutdanning, 2016.Norsk: Dagens samfunn består av et stort mangfold med mennesker med ulike bakgrunner, kulturer og språk. For å fungere i et samfunn er det derfor helt nødvendig at mennesker både respekterer og tolererer hverandre. Som andre grunnleggende ferdigheter må dette læres, og derfor er det viktig at fokuset på respekt og toleranse i skolen blir opprettholdt. For å legge et godt grunnlag for disse verdiene er det viktig å starte arbeidet med respekt og toleranse fra barna er små, og derfor har jeg valgt å belyse dette gjennom problemstillingen: Hvordan kan en KRLE-lærer på 1.trinn arbeide for å legge et godt grunnlag for elevenes respekt og toleranse? Jeg redegjør først begrepene respekt og toleranse, før jeg videre ser på hvordan lærerens rolle og undervisning kan legge et godt grunnlag for elevene.English: Today’s society consists of a large community of people with different backgrounds, cultures and languages. It is therefore of great importance that people both respect and tolerate each other. These skills, like other basic skills, needs to be learned, and for this reason it is important to focus on respect and tolerance being maintained in school. To create a sustainable foundation for these values, it is essential to start working on how to show respect and tolerance with and around the children from a young age, and I have chosen to emphasise this through the question: How can a 1st grade KRLE-teacher work to create a good foundation for the students respect and tolerance? I will begin by clarifying the terms respect and tolerance, before I move on towards how a teacher’s role and lessons can create a good foundation for the pupils

Dung Beetle community and functions along a habitat-disturbance gradient in the Amazon:a rapid assessment of ecological functions associated to biodiversity

Although there is increasing interest in the effects of habitat disturbance on community attributes and the potential consequences for ecosystem functioning, objective approaches linking biodiversity loss to functional loss are uncommon. The objectives of this study were to implement simultaneous assessment of community attributes (richness, abundance and biomass, each calculated for total-beetle assemblages as well as small- and large-beetle assemblages) and three ecological functions of dung beetles (dung removal, soil perturbation and secondary seed dispersal), to compare the effects of habitat disturbance on both sets of response variables, and their relations. We studied dung beetle community attributes and functions in five land-use systems representing a disturbance gradient in the Brazilian Amazon: primary forest, secondary forest, agroforestry, agriculture and pasture. All response variables were affected negatively by the intensification of habitat disturbance regimes, but community attributes and ecological functions did not follow the same pattern of decline. A hierarchical partitioning analysis showed that, although all community attributes had a significant effect on the three ecological functions (except the abundance of small beetles on all three ecological functions and the biomass of small beetles on secondary dispersal of large seed mimics), species richness and abundance of large beetles were the community attributes with the highest explanatory value. Our results show the importance of measuring ecological function empirically instead of deducing it from community metrics

Attitudes and knowledge of shade-coffee farmers towards vertebrates and their ecological functions.

The purpose of this study was to assess farmers&rsquo; attitudes, as well as perceptions and knowledge that shape those attitudes, toward the ecological role of vertebrates inhabiting shaded-coffee farms. We also aimed to determine whether differences existed among two groups of farmers: one that had attended environmental education workshops, and one that had not. We conducted 36 oral interviews of farmers in the region of Cuetzalan, Mexico. All farmers were members of an important regional cooperative, Tosepan Titataniske. In general, farmers&rsquo; attitudes towards birds were positive. Snakes were perceived as useful but dangerous animals. Attitudes towards nonflying mammals were mostly indifferent. Bats were poorly understood and badly perceived. Seed dispersal was perceived as an important ecological function performed by animals. Pollination was also perceived as important, but to a lesser degree. Knowledge about ecological functions was high for seed dispersal, and low for pollination. We found a positive correlation between attendance of educational workshops and the presence of &ldquo;environmentally-friendly&rdquo; attitudes, perceptions, and knowledge. However, a cause-effect relationship could not be clearly established. We suggest that environmental education programs include the objective of increasing the knowledge of people about the ecological functions played by different groups of animals that live in agroecosystems. Particular efforts should be directed toward improving the way in which certain non-charismatic groups of animals, such as bats, are perceived.<br /

The use of indigenous knowledge in development: problems and challenges

The use of indigenous knowledge has been seen by many as an alternative way of promoting development in poor rural communities in many parts of the world. By reviewing much of the recent work on indigenous knowledge, the paper suggests that a number of problems and tensions has resulted in indigenous knowledge not being as useful as hoped for or supposed. These include problems emanating from a focus on the (arte)factual; binary tensions between western science and indigenous knowledge systems; the problem of differentiation and power relations; the romanticization of indigenous knowledge; and the all too frequent decontextualization of indigenous knowledge

Datos preliminares sobre el papel del venado cola blanca Odocoileus virginianus (Artiodactyla: Cervidae) como dispersor de semillas

El papel del venado cola blanca como dispersor endozoócoro de semillas se evaluó a través de la estimación del número de semillas y especies encontradas en las muestras fecales, y el análisis del efecto del paso por el tracto digestivo sobre el porcentaje y la velocidad de germinación en semillas de una especie focal (Acacia schaffneri). En total se encontraron 369 semillas en 98 grupos de pellets. La mayoría de las semillas se apreciaban dañadas o inmaduras, sólo 67 semillas (31 morfoespecies) germinaron. El porcentaje de germinación de semillas de A. schaffneri defecadas tendió a ser mayor que la germinación de semillas control. En nuestro estudio el venado figura como depredador de semillas y ocasionalmente como dispersor de semillas. Sin embargo, nuestros resultados con animales en cautiverio muestran que el venado puede incrementar el porcentaje de germinación de algunas especies.The role of white-tailed deer in endozoochorus seed dispersal was evaluated by estimating the number of seeds and seed species found in fecal samples and assessing the effect of gut passage on germination percentage and speed for a focal seed species (Acacia schaffneri). A total of 369 seeds were found in 98 pellet groups. Most seeds appeared to be damaged or immature, and only 67 seeds (31 morphospecies) germinated. Germination percentage of defecated seeds of A. schaffneri tended to be higher than germination of control seeds. In our study site white-tailed deer appears to be acting mainly as a seed predator for ingested seeds, and occasionally as a seed disperser. Nevertheless, our results using captive animals suggest that white-tailed deer may improve seed germination of particular plant species

Conservation of the endemic dwarf carnivores of Cozumel Island, Mexico.

Cozumel Island, Mexico, harbours two endemic species of dwarf procyonids: the Pygmy Raccoon Procyon pygmaeus and the Dwarf Coati Nasua nelsoni. Both species are Critically Endangered, and are among the world&rsquo;s most threatened Carnivora. Here we summarise the research we have been conducting on their ecology, evolution, genetics, and conservation. We also summarise the conservation initiatives we have been undertaking and promoting in order to advance the conservation of these unique species and their habitats. This effort illustrates the importance of an interdisciplinary approach in conservation science and action in maximising effectiveness. Nevertheless, the precarious status of the species make it imperative to continue and expand the work we have carried out in Cozumel to prevent two imminent global extinctions.<br /