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- Ohlson, Johan, 1979-
(författare)
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Novel sites of A-to-I RNA editing in the mammalian brain
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The number of protein-coding genes are likely not sufficient to account for the complexity of higher organisms. It is plausible that the proteome is responsible for the complexity of an organism.An important mechanism that increases the protein variability is post-transcriptional modifications that alter the pre-mRNA sequence from that encoded in the genome. In this thesis work I have been focusing on a post-transcriptional process where adenosine (A) is deaminated to inosine (I), A-to-I RNA editing. Inosine is read as a guanosine (G) by the translation machinery, editing within coding regions can therefore give rise to more than one protein isoform from a single gene. A-to-I RNA editing is catalyzed by members of the ADAR enzyme family. ADARs have been found in all metazoans tested and two active ADAR proteins, ADAR1 and ADAR2, have been found in mammals. However, recoding by A-to-I editing is a rarely found event in mammals.To detect novel substrates for A-to-I editing we developed an experimental approach to pull down ADAR2 substrates using immunoprecipitations. The captured RNAs were identified by microarray analysis. In this thesis two novel substrates for A-to-I editing are presented that were found using our IP-array approach, in combination with bioinformatic techniques.The transcript coding for the GABAA receptor subunit α3 (Gabra-3) was found to be selectively edited by both ADAR1 and ADAR2. Editing of Gabra-3 recodes an isoleucine to a methionine and it was found to have a negative effect on the Gabra-3 assembly into the receptor. Moreover, the mouse specific CTN-RNA that codes for the CAT2 Transcribed Nuclear-RNA was shown to be hyper-edited by ADAR2.In conclusion, this thesis work has resulted in an experimental method that extracts ADAR substrates. Two novel editing substrates were discovered. Our data adds additional evidence to the fact that RNA editing is of principal significance for a functional brain.
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| 2. |
- Öhman, Johan, 1961-
(författare)
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Den etiska tendensen i utbildning för hållbar utveckling : meningsskapande i ett genomlevandeperspektiv
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis is to contribute to the debate about Education for Sustainable Development (ESD), and provide a practical tool for teachers with which they can relate to ethical and moral learning in the ESD context. This aim is based on the ambition to develop an approach that takes its starting point from our practical experience of ethics and morals, inspired by the later works of Ludwig Wittgenstein and the transactional perspective developed by John Dewey. This implies that ethics and morals are regarded as a human tendency that is observable in action. The central method used to clarify ethical and moral meaning-making is, by the use of examples, to remind of common experiences of how this meaning-making appears in everyday situations. These clarifications are made in order to dissolve (rather than solve) philosophical problems, as well as to create new knowledge. The approach has been applied to four different studies. The first study focuses on the differences between three selective traditions in environmental education: fact-based, normative and pluralistic, with regard to the relationship between facts and values. It is argued that a pluralistic approach can be seen as way of relating facts and values in practice, and consequently that the democratic process neither precedes nor succeeds education but is an integral part of it, and that students therefore are constituted as citizens participating in the progress of sustainable development. The purpose of the second study is to suggest an approach that allows in situ analysis of how individuals’ prior experiences are included in the processes of moral meaning-making. A concrete example shows how individuals can transform the moral discourse in different situations. In the third study, it is suggested that the ethical tendency can be recognised as a communication in which certain values and actions are treated as if they were universally good and right. Three different kinds of situations in which this communication appears are highlighted: personal moral reactions, norms for correct behaviour and ethical reflections.The diverse conditions for learning in these situations are discussed, and specific notice is taken of the risk of indoctrination in ESD. The fourth study addresses the question of how to understand and deal with criticism in a pluralistic educational approach. Through reminders of how criticism appears in everyday practice, it is argued that criticism does not necessarily have to be understood theoretically. Criticism can also be seen as the diverse ways in which human beings morally react, encounter different norms and ethically reflect.
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| 3. |
- Öhman, Johan, 1973-
(författare)
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Upscaling of Flow, Transport, and Stress-effects in Fractured Rock
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of many applications of geohydraulic modelling is assessing the suitability of a site to host a nuclear waste repository. This modelling task is complicated by scale-dependent heterogeneity and coupled thermo-hydro-mechanical (THM) processes. The objective here was to develop methods for (i) upscaling flow and transport in fractured media from detailed-scale data and (ii) accounting for THM-induced effects on regional-scale transport. An example field data set was used for demonstration.A systematic framework was developed where equivalent properties of flow, transport, and stress-effects were estimated with discrete fracture network (DFN) modelling, at some block scale, and then transferred to a regional-scale stochastic continuum (SC) model. The selected block scale allowed a continuum approximation of flow, but not of transport. Instead, block-scale transport was quantified by transit time distributions and modelled with a particle random walk method at the regional scale.An enhanced SC-upscaling approach was developed to reproduce the DFN flow results more simply. This required: (i) weighting of the input well-test data by their conductivity-dependent test volumes and (ii) conductivity-dependent correlation structure. Interestingly, the best-fitting correlation structure resembled the density function of DFN transmissivities. Channelized transport, over distances exceeding the block scale, was modelled with a transport persistence length. A linear relationship was found between this persistence length and the macroscale dispersion coefficient, with a slope equal to a representative mean block-scale dispersion coefficient.A method was also developed to combine well-test data and rock-mechanical data in estimating fracture transmissivities, and its application was demonstrated.Finally, an overall sequential THM analysis was introduced allowing the estimation of the significance of waste-related thermo-mechanical (TM) effects on regional transport; here TM effects are calculated separately and their impact on fracture transmissivities were incorporated into the hybrid framework. For the particular case, their effects on regional-scale transport were small.
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