Theoretical studies of Membrane Proteins : Properties, Prediction Methods and Genome-wide analysis

Membrane proteins are a large and important class of proteins. They are responsible for several of the key functions in a living cell, e.g. transport of nutrients and ions, cell-cell signaling, and cell-cell adhesion. Despite their importance it has not been possible to study their structure and organization in much detail because of the difficulty to obtain 3D structures. In this thesis theoretical studies of membrane protein sequences and structures have been carried out by analyzing existing experimental data. The data comes from several sources including sequence databases, genome sequencing projects, and 3D structures. Prediction of the membrane spanning regions by hydrophobicity analysis is a key technique used in several of the studies. A novel method for this is also presented and compared to other methods. The primary questions addressed in the thesis are: What properties are common to all membrane proteins? What is the overall architecture of a membrane protein? What properties govern the integration into the membrane? How many membrane proteins are there and how are they distributed in different organisms? Several of the findings have now been backed up by experiments. An analysis of the large family of G-protein coupled receptors pinpoints differences in length and amino acid composition of loops between proteins with and without a signal peptide and also differences between extra- and intracellular loops. Known 3D structures of membrane proteins have been studied in terms of hydrophobicity, distribution of secondary structure and amino acid types, position specific residue variability, and differences between loops and membrane spanning regions. An analysis of several fully and partially sequenced genomes from eukaryotes, prokaryotes, and archaea has been carried out. Several differences in the membrane protein content between organisms were found, the most important being the total number of membrane proteins and the distribution of membrane proteins with a given number of transmembrane segments. Of the properties that were found to be similar in all organisms, the most obvious is the bias in the distribution of positive charges between the extra- and intracellular loops. Finally, an analysis of homologues to membrane proteins with known topology uncovered two related, multi-spanning proteins with opposite predicted orientations. The predicted topologies were verified experimentally, providing a first example of "divergent topology evolution".

Medborgarmönstringen inom högern 1915–1936 : En begreppshistorisk och diskursorienterad undersökning av medborgarbegreppets utbredning, mening och funktion inom Allmänna valmansförbundet

During the 1920s and 1930s, the Swedish right-wing party Allmänna valmansförbundet (AVF) made citizen into a key concept within their political vocabulary and practice. This thesis examines the distribution, meaning and function of the concept of citizen within the AVF between 1915 and 1936. By using theoretical and methodological perspectives from both the English (Skinner) and German (Koselleck) side of conceptual history vis-à-vis Begriffsgeschischte, this study illuminates how a discursive framework took place within the AVF and expanded throughout the organisation. The constitutional reforms 1918/1921 and the organisational strength from opposite parties, stressed the importance for the AVF to assemble the citizens around conservative value laden concepts: responsibility, ansvar, and public participation, offentlighet. This new situation in political and social life, pushed the AVF towards a reorganisation. The aim was to educate the masses, women and youth into conservative citizens. Citizen became the sole tool in (i) upholding the traditional heritage between folk–state, and (ii) enabling the AVF citizen discourse to spread throughout the society. This study shows the multiple meaning and functions of the citizen concept within the AVF.  It provides a new understanding of how collective concepts became an important part of the struggle for power during the democratization process in Swedish political history and must in that respect be seen as an antithesis to the collective concepts of the Social Democratic Party during this period.