BRICHOS

Lung surfactant protein C (SP-C) is a 35-residue, transmembrane (TM) peptide that is extremely hydrophobic and lacks known homologous proteins. Due to a high content in Val residues in the α-helical TM part, SP-C can spontaneously convert into β-sheet aggregates. We show here that SP-C forms amyloid in interstitial lung disease (ILD) caused by mutations in the C-terminal part of proSP-C (CTC). CTC has been predicted to contain a ∼100-residue BRICHOS domain, found in 12 protein families with a wide range of functions and disease associations, such as respiratory distress syndrome, dementia and cancer. We hypothesised that the BRICHOS domain can act as a chaperone, preventing proprotein from misfolding during biosynthesis. Recombinant CTC can bind to lipid associated non-helical SP-C and this interaction results in an increased α-helical content in the mature SP-C peptide. Wildtype CTC can also stabilize proSP-C(1-58), which lacks the BRICHOS domain, and a proSP-C mutant in HEK293 cells. CTC binds selectively peptides derived from the TM part of SP-C and to residues that promote membrane insertion. CTC can also bind to other hydrophobic peptides, in particular the amyloid β-peptide (Aβ) associated with Alzheimer disease. CTC and Bri2 BRICHOS can prevent fibril formation of Aβ40 and Aβ42 far below stoichiometric amounts, indicating that BRICHOS may be useful in future therapy. The crystal structure of the BRICHOS domain from CTC shows a novel fold with a central β-sheet flanked by α-helices on either side. Many of the hydrophobic residues in the β-sheet are conserved and many of the point mutations associated with ILD coincide with these residues, suggesting that they are involved in the function of the BRICHOS domain possibly by binding substrate peptides. Taken together, results in this thesis, suggest that BRICHOS is a novel anti-amyloid chaperone domain and mutations that lead to BRICHOS dysfunction cause ILD and amyloid disease

The Riddle Johanna Möller : A discourse analysis of the Swedish news portrayal of Johanna Möller.

The objective of this bachelor thesis was to examine how the lifetime sentenced Johanna Möller, who in 2016 persuaded her boyfriend to kill her parents, is portrayed in Swedish news journalism. We analyzed 46 articles published in Swedish tabloid describing her character after she received her sentence in August 2017. The research questions were: How is Johanna Möller portrayed as a character? How is Johanna Möller portrayed as a criminal? How is Johanna Möller portrayed as a woman? Fairclough’s critical discourse analysis (CDA) and the associated three-dimensional model was conducted to find and dissect discourses in the articles. We carried out the analysis from a gender-related theoretical perspective and drew parallels to earlier research concerning media and crime.  Through the analysis, five discourses could be identified; The Non-agent, The Evil Woman and The Good Boy, Temptress, The Bad Mother and She Who Never Does Right.    Not seldom is Johanna Möller described as promiscuous, evil and manipulative. Her role as a mother is also being repeatedly criticized even though her actual crimes are not related to her motherhood. Accordingly, the journalists are constantly looking for an explanation for her abnormal behaviour and she is often being described as a cold hearted yet emotional person, which can be seen as a significant paradox in the portrayal of her. Our conclusion is that no matter Johanna Möller’s actual crimes, her role as a woman has become the most present aspect of her actions.

BRICHOS Domains Efficiently Delay Fibrillation of Amyloid beta-Peptide

Amyloid diseases such as Alzheimer, Parkinson, and prion diseases are associated with a specific form of protein mis-folding and aggregation into oligomers and fibrils rich in beta-sheet structure. The BRICHOS domain consisting of similar to 100 residues is found in membrane proteins associated with degenerative and proliferative disease, including lung fibrosis (surfactant protein C precursor; pro-SP-C) and familial dementia (Bri2). We find that recombinant BRICHOS domains from Bri2 and pro-SP-C prevent fibril formation of amyloid beta-peptides (A beta(40) and A beta(42)) far below the stoichiometric ratio. Kinetic experiments show that a main effect of BRICHOS is to prolong the lag time in a concentration-dependent, quantitative, and reproducible manner. An ongoing aggregation process is retarded if BRICHOS is added at any time during the lag phase, but it is too late to interfere at the end of the process. Results from circular dichroism and NMR spectroscopy, as well as analytical size exclusion chromatography, imply that A beta is maintained as an unstructured monomer during the extended lag phase in the presence of BRICHOS. Electron microscopy shows that although the process is delayed, typical amyloid fibrils are eventually formed also when BRICHOS is present. Structural BRICHOS models display a conserved array of tyrosine rings on a five-stranded beta-sheet, with inter-hydroxyl distances suited for hydrogen-bonding peptides in an extended beta-conformation. Our data imply that the inhibitory mechanism is reliant on BRICHOS interfering with molecular events during the lag phase