| 1. |
- Andersson, Sören, 1957-, et al.
(författare)
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CHIMERIC MOMP ANTIGEN
- 2015
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Patent (populärvet., debatt m.m.)
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| 2. |
- Andersson, Sören, 1957-, et al.
(författare)
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Chimeric MOMP antigen
- 2014
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Patent (populärvet., debatt m.m.)abstract
- The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.
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| 3. |
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| 4. |
- Aisenbrey, Christopher, et al.
(författare)
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SOD1 associates to membranes in its folded apo-state
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Annan publikation (populärvet., debatt m.m.)abstract
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied by misfolding and intracellular deposition of superoxide dismutase 1 (SOD1). Although the molecular details behind this misfolding process are yet poorly understood, increasing evidence suggest that SOD1 is most susceptible to misfolding in its metal-free and relatively unstable apo-state. Here, we addressed the question, if misfolding and aggregation of SOD1 involves erroneous interactions with membranes as has been implicated for the Aβ peptide in Alzheimers disease. To examine this possibility we subjected various apo SOD1 variants to the presence of different membrane systems. The results reveal that wild type apoSOD1 but to less extent destabilized ALS mutations interact with charged vesicles under physiologically relevant conditions, thereby acquiring pronounced helical structural features. As the data further show, the protein binds to the membranes by an electrostatically driven mechanism, which requires a folded apo-state conformation and a negative membrane surface potential. Unfolded SOD1 molecules show no appreciable affinity to the membrane surfaces yielding a correlation between increased stability, i. e. occupancy of folded molecules and extend of membrane association. Since this trend opposes the correlation between decreased SOD1 stability and progression of neural damage, the results suggest that membrane association is not part of the ALS mechanism. An explanation could be that the observed membrane association of apo SOD1 is reversible and does not ‘bleed out’ in irreversible aggregation as observed for other precursors of protein-misfolding diseases.
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| 5. |
- Bellotti, Vittorio, et al.
(författare)
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Robert Kisilevsky, MD, PhD, 1937–2019
- 2019
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Ingår i: Amyloid. - : Taylor & Francis. - 1350-6129 .- 1744-2818. ; 26:4, s. 179-179
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 6. |
- Byström, Roberth, 1971-, et al.
(författare)
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Electrostatic interactions between negatively charged phospolipid membranes and SOD1 protein : Effect of charge changing fALS mutations
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Annan publikation (populärvet., debatt m.m.)abstract
- The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is closely connected to single site mutations of the Cu/Zn superoxide dismutase (SOD1) protein, whose pathological conversion into misfolded aggregates is a hallmark of ALS. To explore the impact of protein net charge changing ALS relevant SOD1 mutations on their ability to interact with neuronal membranes and the consequences for their folding behaviour, we studied by circular dichroism the conformational changes of the SOD1pWT, SOD1N86D and SOD1N86K species in their apo-state in the presence of increasing amounts of negatively charged lipid bilayers.. The results clearly indicate an electrostatically driven association process, where the association event induces a pronounced increase in the helical character of the pWT and the N86D species, characterized by long patient survival times. To the opposite, the charge reducing N86K mutation shows more pronounced β-like features in the presence of membranes in comparison to the other two species; an observation which most likely reflects its reduced stability in its apo-state in combination with a very fast ALS progression.
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| 7. |
- Byström, Roberth, 1971-, et al.
(författare)
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Identification of property outliers among ALS-associated SOD1 mutations : Common effect on surface hydrogen bonds
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Annan publikation (populärvet., debatt m.m.)abstract
- In good accord with the protein-aggregation hypothesis for neurodegenerative diseaseALS-associated SOD1 mutations are found to reduce structural stability or netrepulsive charge. Moreover there are weak indications that the ALS diseaseprogression is correlated with the degree of mutational impact on the SOD1 structure.A bottleneck for obtaining more conclusive information about these structure-diseaserelationships, however, is the large intrinsic variability in patient survival times andinsufficient disease statistics for the majority of ALS-provoking mutations. As analternative test of the structure-disease relationship we focus here on the SOD1 amutation that appears to be outliers in the data set. The results identify several ALSprovokingmutations whose only effect on apo SOD1 is the elimination orintroduction of a single charge, i.e., D76V/Y, D101N and N139D/K. Thethermodynamic stability and folding behaviour of these mutants are indistinguishablefrom the wildtype control, showing that structurally benign replacements of individualsurface charges are sufficient to trigger ALS. Moreover, D101N is a clear outlier inthe plot of stability loss vs. patient survival time by having too rapid diseaseprogression. Common to the identified mutations is that they truncate conserved saltlinksand/or H-bond networks in the functional loops IV or VII. The results show thatthe local impact of ALS-associated mutations on the SOD1 molecule can sometimesoverrun their global effects on stability and net repulsive charge, and point at theanalysis of property outliers as an efficient strategy for mapping out new ALSprovokingfeatures.
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| 8. |
- Carlsson, Pernilla, et al.
(författare)
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Heparan sulfate biosynthesis: Characterization of an NDST1 splice variant
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Annan publikation (populärvet., debatt m.m.)abstract
- N-Deacetylase/N-sulfotransferases (NDSTs) are Golgi-located enzymes involved in the biosynthesis of heparan sulfate. They are bifunctional enzymes responsible for N-deacetylation of N-acetylglucosamine residues followed by N-sulfation of the generated free amino groups. In this paper we have identified and characterized a splice variant of NDST1 mRNA. The alternatively spliced mRNA transcript was shown to be present in varying amounts in different adult and embryonic mouse tissues. The protein resulting from translation of the spliced transcript (NDST1S) lacks the C-terminal half of fullength NDST and appears to be devoid of enzyme activity. As shown in HEK 293 cells overexpressing NDST1, a high expression of the splice variant resulted in reduced levels of NDST1. Unexpectedly, the level of N-sulfation was largely unaltered in heparan sulfate produced in NDST1S overexpressing cells while 6-O-sulfation was elevated and 2-O-sulfation was reduced. NDST1S shares the ability of NDST1 to interact with EXT2, one of the components of the heparan sulfate copolymerase. We speculate that NDST1S may alter the composition of the tentaive enzyme complex, the GAGosome, resulting in changes in the structure of heparan sulfate synthesized.
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| 9. |
- Dagälv, Anders, et al.
(författare)
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Cell surface mast cell proteoglycans identified as heparin-substituted syndecan-2
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Annan publikation (populärvet., debatt m.m.)abstract
- Connective tissue type mast cells isolated from the peritoneal cavity of mice and then cultured in vitro have been used to answer the question if one cell at a given time point can synthesize heparan sulfate chains with different structure. Characterization of cell surface proteoglycans made by the cells demonstrated that they were identical to syndecan-2, substituted with heparin chains. Ion exchange chromatography showed that the syndecan heparin chains behaved identically as heparin chains recovered from serglycin, inside the cells. This was also the case when mast cells from NDST2 deficient mice were studied. This time, syndecan-2 as well as serglycin derived polysaccharide chains had a lower but identical charge density. We conclude that mast cells only synthesize one kind of heparan sulfate/heparin chain at a time and that polysaccharide chains of identical structure will be found at the cell surface and inside the cell.
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| 10. |
- Dagälv, Anders, et al.
(författare)
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Lack of both lethality and defective in vitro differentiation of embryonic stem cells N-deacetylase/N-sulfotransferase 1 and 2 causes early embryonic
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Annan publikation (populärvet., debatt m.m.)abstract
- NDSTs (N-deacetylase/N-sulfotransferases) are enzymes responsible for N-sulfation during heparan sulfate and heparin biosynthesis. While lack of NDST2 results in defective mast cells and NDST1 deficiency causes neonatal death and lung, skeletal and brain defects, lack of both isoforms is not compatible with embryonic development. We here show that NDST1/2-/- embryos die before E6.5 and that embryos dissected out at E5.5 lack parts of the embryo/extraembryonic tissue. Consistent with their in vivo behavior, in vitro cultured NDST1/2 deficient embryos displayed impaired ability of inner cell mass proliferation. In addition, markers for all the three germ layers had a disturbed expression pattern in isolated NDST1/2 deficient embryonic stem (ES) cells. Characterization of heparan sulfate (HS) structure in control ES cells and in ES cells lacking NDST1, NDST2 or both NDST1 and NDST2 revealed big differences. As expected, control cells synthesized HS with the highest degree of sulfation closely followed by HS from NDST2-/- cells, which in turn was more sulfated than HS produced by NDST1-/- cells. HS from NDST1/2-/- cells was almost devoid of sulfate groups. Notably, lack of one NDST isoform did not result in increased expression of any of the others. While all cell types except the NDST1/2-/- cells produced HS with a higher degree of sulfation when allowed to differentiate for 8 days, HS from control cells was still more heavily sulfated than that produced by NDST2-/- cells followed by the HS of NDST1-/- cells. The increase in sulfation was paralleled by increased expression of NDST transcripts and could also be recorded as increased N-sulfotransferase activity of cell lysates. While NDST1/2 deficient ES cells were unable to differentiate into beating cardiomyocytes all NDST1-/- and control embryoid bodies had started to beat after 4 days of culture. Surprisingly, NDST2 deficiency resulted in delayed cardiomyocyte differentiation.
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