| 1. |
- Abelein, Axel, et al.
(författare)
-
The hairpin conformation of the amyloid beta peptide is an important structural motif along the aggregation pathway
- 2014
-
Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 19:4-5, s. 623-634
-
Forskningsöversikt (refereegranskat)abstract
- The amyloid beta (A beta) peptides are 39-42 residue-long peptides found in the senile plaques in the brains of Alzheimer's disease (AD) patients. These peptides self-aggregate in aqueous solution, going from soluble and mainly unstructured monomers to insoluble ordered fibrils. The aggregation process(es) are strongly influenced by environmental conditions. Several lines of evidence indicate that the neurotoxic species are the intermediate oligomeric states appearing along the aggregation pathways. This minireview summarizes recent findings, mainly based on solution and solid-state NMR experiments and electron microscopy, which investigate the molecular structures and characteristics of the A beta peptides at different stages along the aggregation pathways. We conclude that a hairpin-like conformation constitutes a common motif for the A beta peptides in most of the described structures. There are certain variations in different hairpin conformations, for example regarding H-bonding partners, which could be one reason for the molecular heterogeneity observed in the aggregated systems. Interacting hairpins are the building blocks of the insoluble fibrils, again with variations in how hairpins are organized in the cross-section of the fibril, perpendicular to the fibril axis. The secondary structure propensities can be seen already in peptide monomers in solution. Unfortunately, detailed structural information about the intermediate oligomeric states is presently not available. In the review, special attention is given to metal ion interactions, particularly the binding constants and ligand structures of A beta complexes with Cu(II) and Zn(II), since these ions affect the aggregation process(es) and are considered to be involved in the molecular mechanisms underlying AD pathology.
|
|
| 2. |
- Behrendt, Christian-Alexander, et al.
(författare)
-
International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection
- 2018
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 56:2, s. 217-237
-
Tidskriftsartikel (refereegranskat)abstract
- Objective/Background: To achieve consensus on the minimum core data set for evaluation of peripheral arterial revascularisation outcomes and enable collaboration among international registries.Methods: A modified Delphi approach was used to achieve consensus among international vascular surgeons and registry members of the International Consortium of Vascular Registries (ICVR). Variables, including definitions, from registries covering open and endovascular surgery, representing 14 countries in ICVR, were collected and analysed to define a minimum core data set and to develop an optimum data set for registries. Up to three different levels of variable specification were suggested to allow inclusion of registries with simpler versus more complex data capture, while still allowing for data aggregation based on harmonised core definitions.Results: Among 31 invited experts, 25 completed five Delphi rounds via internet exchange and face to face discussions. In total, 187 different items from the various registry data forms were identified for potential inclusion in the recommended data set. Ultimately, 79 items were recommended for inclusion in minimum core data sets, including 65 items in the level 1 data set, and an additional 14 items in the more specific level 2 and 3 recommended data sets. Data elements were broadly divided into (i) patient characteristics; (ii) comorbidities; (iii) current medications; (iv) lesion treated; (v) procedure; (vi) bypass; (vii) endarterectomy (viii) catheter based intervention; (ix) complications; and (x) follow up.Conclusion: A modified Delphi study allowed 25 international vascular registry experts to achieve a consensus recommendation for a minimum core data set and an optimum data set for peripheral arterial revascularisation registries. Continued global harmonisation of registry infrastructure and definition of items will overcome limitations related to single country investigations and enhance the development of real world evidence.
|
|
| 3. |
|
|
| 4. |
- Budtz-Lilly, Jacob, et al.
(författare)
-
Editor's Choice - The Impact of Centralisation and Endovascular Aneurysm Repair on Treatment of Ruptured Abdominal Aortic Aneurysms Based on International Registries
- 2018
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 56:2, s. 181-188
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Current management of ruptured abdominal aortic aneurysms (RAAA) varies among centres and countries, particularly in the degree of implementation of endovascular aneurysm repair (EVAR) and levels of vascular surgery centralisation. This study assesses these variations and the impact they have on outcomes.Materials and methods: RAAA repairs from vascular surgical registries in 11 countries, 2010-2013, were investigated. Data were analysed overall, per country, per treatment modality (EVAR or open aortic repair [OAR]), centre volume (quintiles IV), and whether centres were predominantly EVAR (>= 50% of RAAA performed with EVAR [EVAR(p)]) or predominantly OAR [OAR(p)]. Primary outcome was peri-operative mortality. Data are presented as either mean values or percentages with 95% CI within parentheses, and compared with chi-square tests, as well as with adjusted OR.Results: There were 9273 patients included. Mean age was 74.7 (74.5-74.9) years, and 82.7% of patients were men (81.9-83.6). Mean AAA diameter at rupture was 7.6 cm (7.5-7.6). Of these aneurysms, 10.7% (10.0-11.4) were less than 5.5 cm. EVAR was performed in 23.1% (22.3-24.0). There were 6817 procedures performed in OAR(p) centres and 1217 performed in EVAR(p) centres. Overall peri-operative mortality was 28.8% (27.9-29.8). Peri-operative mortality for OAR was 32.1% (31.0-33.2) and for EVAR 17.9% (16.3-19.6), p < .001, and the adjusted OR was 0.38 (0.31-0.47), p < .001. The peri-operative mortality was 23.0% in EVAR(p) centres (20.6-25.4), 29.7% in OAR(p) centres (28.6-30.8), p < .001; adjusted OR = 0.60 (0.46-0.78), p < .001. Perioperative mortality was lower in the highest volume centres (QI > 22 repairs per year), 23.3% (21.2-25.4) than in QII-V, 30.0% (28.9-31.1), p < .001. Peri-operative mortality after OAR was lower in high volume centres compared with the other centres, 25.3% (23.0-27.6) and 34.0% (32.7-35.4), respectively, p < .001. There was no significant difference in peri-operative mortality after EVAR between centres based on volume.Conclusions: Peri-operative mortality is lower in centres with a primary EVAR approach or with high case volume. Most repairs, however, are still performed in low volume centres and in centres with a primary OAR strategy. Reorganisation of acute vascular surgical services may improve outcomes of RAAA repair.
|
|
| 5. |
|
|
| 6. |
- Ghalebani, Leila, et al.
(författare)
-
pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-beta peptide
- 2012
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 421:3, s. 554-560
-
Tidskriftsartikel (refereegranskat)abstract
- Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer's disease amyloid plaques. The amyloid-beta (A beta) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with N-15- and C-13,N-15-labeled A beta(1-40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to AD may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the AD peptide under these conditions.
|
|
| 7. |
|
|
| 8. |
- Henry, Lucy A., et al.
(författare)
-
Hebb repetition learning in adolescents with intellectual disabilities
- 2022
-
Ingår i: Research in Developmental Disabilities. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0891-4222 .- 1873-3379. ; 125
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundHebb repetition learning is a form of long-term serial order learning that can occur when sequences of items in an immediate serial recall task are repeated. Repetition improves performance because of the gradual integration of serial order information from short-term memory into a more stable long-term memory trace.AimsThe current study assessed whether adolescents with non-specific intellectual disabilities showed Hebb repetition effects, and if their magnitude was equivalent to those of children with typical development, matched for mental age.MethodsTwo immediate serial recall Hebb repetition learning tasks using verbal and visuospatial materials were presented to 47 adolescents with intellectual disabilities (11–15 years) and 47 individually mental age-matched children with typical development (4–10 years).ResultsBoth groups showed Hebb repetition learning effects of similar magnitude, albeit with some reservations. Evidence for Hebb repetition learning was found for both verbal and visuospatial materials; for our measure of Hebb learning the effects were larger for verbal than visuospatial materials.ConclusionsThe findings suggested that adolescents with intellectual disabilities may show implicit long-term serial-order learning broadly commensurate with mental age level. The benefits of using repetition in educational contexts for adolescents with intellectual disabilities are considered.
|
|
| 9. |
- Henry, Lucy A., et al.
(författare)
-
The reliability of Hebb repetition learning and its association with language and reading in adolescents with intellectual disabilities
- 2024
-
Ingår i: Cortex. - : ELSEVIER MASSON, CORP OFF. - 0010-9452 .- 1973-8102. ; 177, s. 253-267
-
Tidskriftsartikel (refereegranskat)abstract
- Hebb repetition learning (HRL) refers to neurodevelopmental processes characterised by repeated stimulus exposure without feedback, which result in changes in behaviour and/or responses, e.g., long-term learning of serial order. Here, we investigate effects of HRL on serial order memory. The present research aimed to assess the reliability of new HRL measures and investigate their relationships with language and reading skills (vocabulary, grammar, word reading) in adolescents with intellectual disability (ID). A comparison group of children of similar mental age with typical development (TD) was also assessed. ID and TD groups were tested on HRL tasks, evaluating test-retest and split-half reliability. The relationship between HRL and language and reading was analysed after accounting for the influence of mental age and verbal short-term memory. The HRL tasks displayed moderate test-retest (and split-half) reliability, HRL tasks with different stimuli (verbal, visual) were related, and we identified issues with one method of HRL scoring. The planned regression analyses failed to show relationships between HRL and language/reading skills in both groups when mental age, a very strong predictor, was included. However, further exploratory regression analyses without mental age revealed HRL's predictive capabilities for vocabulary in the ID group and reading in the TD group, results which need further investigation and replication. HRL displays promise as a moderately reliable metric and exhibits varied and interpretable predictive capabilities for language and reading skills across groups. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC
|
|
| 10. |
- Liegnell, Rasmus, et al.
(författare)
-
Elevated plasma lactate levels via exogenous lactate infusion do not alter resistance exercise-induced signaling or protein synthesis in human skeletal muscle.
- 2020
-
Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319, s. E792-E804
-
Tidskriftsartikel (refereegranskat)abstract
- Lactate has been implicated as a potential signaling molecule. In myotubes, lactate incubation increases mTORC1- and ERK-signaling and induces hypertrophy, indicating that lactate could be a mediator of muscle adaptations to resistance exercise. However, the potential signaling properties of lactate, at rest or with exercise, have not been explored in human tissue. In a cross-over design study, 8 men and 8 women performed one-legged resistance exercise while receiving venous infusion of saline or sodium lactate. Blood was sampled repeatedly, and muscle biopsies were collected at rest and at 0, 90,180 min and 24 h after exercise. The primary outcomes examined were intracellular signaling, fractional protein synthesis rate (FSR), and blood/muscle levels of lactate and pH. Post-exercise blood lactate concentrations were 130% higher in the Lactate trial (3.0 vs 7.0 mmol×l-1, p<0.001) whereas muscle levels were only marginally higher (27 vs 32 mmol×kg-1 d.w., p=0.003) compared to the Saline-trial. Post-exercise blood pH was higher in the Lactate-trial (7.34 vs 7.44, p<0.001), with no differences in intramuscular pH. Exercise increased the phosphorylation of mTORS2448 (~40%), S6K1T389 (~3-fold), and p44T202/T204 (~80%) during recovery, without any differences between trials. FSR over the 24-h recovery period did not differ between the Saline (0.067 %/h) and Lactate (0.062 %/h) trials. This study does not support the hypothesis that blood lactate levels can modulate anabolic signaling in contracted human muscle. Further in vivo research investigating the impact of exercised versus rested muscle and the role of intramuscular lactate is needed to elucidate its potential signaling properties.
|
|
| 11. |
- Lindgren, Joel, et al.
(författare)
-
N-terminal engineering of amyloid-beta-binding Affibody molecules yields improved chemical synthesis and higher binding affinity
- 2010
-
Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2319-2329
-
Tidskriftsartikel (refereegranskat)abstract
- The aggregation of amyloid-beta (A beta) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease Molecules binding with high affinity and selectivity to A beta-peptides are important tools for investigating the aggregation process An A beta-binding Affibody molecule, Z(A beta 3), has earlier been selected by phage display and shown to bind A beta(1-40) with nanomolar affinity and to inhibit A beta-peptide aggregation In this study, we create truncated functional versions of the Z(A beta 3) Affibody molecule better suited for chemical synthesis production Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges The N-terminally truncated Affibody molecules Z(A beta 3)(12-58), Z(A beta 3)(15-58), and Z(A beta 3)(18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule Z(A beta 3)(1-58) Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, Z(A beta 3)(18-58), exhibited complete loss of binding to the A beta(1-40)-peptide, while the Z(A beta 3)(12-58) and Z(A beta 3)(15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the A beta(1-40)-peptide compared to the full-length Affibody molecule Nuclear magnetic resonance spectroscopy showed that the structure of A beta(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the A beta(1-40)-peptide in complex with the full-length Z(A beta 3) Affibody molecule This indicates that the N-terminally truncated Affibody molecules Z(A beta 3)(12-58) and Z(A beta 3)(15-58) are highly promising for further engineering and future use as binding agents to monomeric A beta(1-40)
|
|
| 12. |
- Lindgren, Joel, et al.
(författare)
-
N-terminal engineering of amyloid-β-binding Affibody molecules yields improved chemical synthesis and higher binding affinity
- 2010
-
Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2319-2329
-
Tidskriftsartikel (refereegranskat)abstract
- The aggregation of amyloid-beta (A beta) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease Molecules binding with high affinity and selectivity to A beta-peptides are important tools for investigating the aggregation process An A beta-binding Affibody molecule, Z(A beta 3), has earlier been selected by phage display and shown to bind A beta(1-40) with nanomolar affinity and to inhibit A beta-peptide aggregation In this study, we create truncated functional versions of the Z(A beta 3) Affibody molecule better suited for chemical synthesis production Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges The N-terminally truncated Affibody molecules Z(A beta 3)(12-58), Z(A beta 3)(15-58), and Z(A beta 3)(18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule Z(A beta 3)(1-58) Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, Z(A beta 3)(18-58), exhibited complete loss of binding to the A beta(1-40)-peptide, while the Z(A beta 3)(12-58) and Z(A beta 3)(15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the A beta(1-40)-peptide compared to the full-length Affibody molecule Nuclear magnetic resonance spectroscopy showed that the structure of A beta(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the A beta(1-40)-peptide in complex with the full-length Z(A beta 3) Affibody molecule This indicates that the N-terminally truncated Affibody molecules Z(A beta 3)(12-58) and Z(A beta 3)(15-58) are highly promising for further engineering and future use as binding agents to monomeric A beta(1-40)
|
|
| 13. |
- Pettersson, John Sören, et al.
(författare)
-
Making PRIME Usable
- 2005
-
Ingår i: Proceedings of the 2005 symposium on Usable privacy and security. - New York, New York, USA : Association for Computing Machinery (ACM).
-
Konferensbidrag (refereegranskat)abstract
- Privacy-enhanced Identity Management can enable users to retain and maintain informational self-determination in our networked society. This paper describes the usability research work that has been done within the first year of the European Union project on “Privacy and Identity Management for Europe” (PRIME). It primarily discusses and compares three alternative UI paradigms for privacy-enhanced Identity Management, and presents how important legal privacy principles derived from the European Union Directives have been mapped into suggestions of user interface solutions for PRIME. Besides, it discusses results and encountered problems from conducted usability tests on mock-ups implementing the different UI paradigms and proposes means for addressing those problems. The paper concludes with remarks on the characteristics of usability work for privacy-enhancing technologies.
|
|
| 14. |
- Poloczek, Sebastian, et al.
(författare)
-
Strategic verbal rehearsal in adolescents with mild intellectual disabilities: A multi-centre European study
- 2016
-
Ingår i: Research in Developmental Disabilities. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0891-4222 .- 1873-3379. ; 58, s. 83-93
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is a long-held view that verbal short-term memory problems of individuals with intellectual disabilities (ID) might be due to a deficit in verbal rehearsal. However, the evidence is inconclusive and word length effects as indicator of rehearsal have been criticised. Aim amp; method: The aim of this multi-site European study was to investigate verbal rehearsal in adolescents with mild ID (n = 90) and a comparison group of typically developing children matched individually for mental age (MA, n = 90). The investigation involved: (1) a word length experiment with non-verbal recall using pointing and (2) self-paced inspection times to infer whether verbal strategies were utilised when memorising a set of pictorial items. Results: The word length effect on recall did not interact with group, suggesting that adolescents with ID and MA comparisons used similar verbal strategies, possibly phonological recoding of picture names. The inspection time data suggested that high span individuals in both groups used verbal labelling or single item rehearsal on more demanding lists, as long named items had longer inspection times. Conclusions: The findings suggest that verbal strategy use is not specifically impaired in adolescents with mild ID and is mental age appropriate, supporting a developmental perspective. (C) 2016 Elsevier Ltd. All rights reserved.
|
|
| 15. |
- Sjöström, Mats, et al.
(författare)
-
Mandibular resection in patients with head and neck cancer : acute and long-term complications after reconstruction
- 2022
-
Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 142:1, s. 78-83
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient.Aims/Objectives: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions.Material and Methods: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24).Results: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien–Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication.Conclusions: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien–Dindo grade IIIa–V events was significantly lower for patients treated with primary closure without grafts. Significance: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.
|
|
| 16. |
- Sävström, Johan, et al.
(författare)
-
Redefining the social contract in Africa
- 2021
-
Rapport (populärvet., debatt m.m.)abstract
- This is a summary note of the virtual seminar The Nordic contribution to EU-Africa cooperation in times of threatened multilateralism held on 30 November 2020. Thought leaders, scholars and policymakers from Africa and Europe discussed the need to strengthen the social contract in Africa, and how the Nordic countries can contribute to the future of EU-Africa relations.
|
|
| 17. |
- Wallin, Cecilia, et al.
(författare)
-
Metal ion coordination delays amyloid-β peptide self-assembly by forming an aggregation-inert complex
- 2020
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:21, s. 7224-7234
-
Tidskriftsartikel (refereegranskat)abstract
- A detailed understanding of the molecular pathways for amyloid-β (Aβ) peptide aggregation from monomers into amyloid fibrils, a hallmark of Alzheimer’s disease, is crucial for the development of diagnostic and therapeutic strategies. We investigate the molecular details of peptide fibrillization in vitro by perturbing this process through addition of differently charged metal ions. Here, we used a monovalent probe, the silver ion, that, similarly to divalent metal ions, binds to monomeric Aβ peptide and efficiently modulates Aβ fibrillization. On the basis of our findings, combined with our previous results on divalent zinc ions, we propose a model that links the microscopic metal ion binding to Aβ monomers to its macroscopic impact on the peptide self-assembly observed in bulk experiments. We found that sub-stoichiometric concentrations of the investigated metal ions bind specifically to the N-terminal region of Aβ, forming a dynamic, partially compact complex. The metal ion bound state appears to be incapable of aggregation, effectively reducing the available monomeric Aβ pool for incorporation into fibrils. This is especially reflected in a decreased fibril-end elongation rate. However, since the bound state is significantly less stable than the amyloid state, Aβ peptides are only transiently redirected from fibril formation and eventually almost all Aβ monomers are integrated into fibrils. Taken together, these findings unravel the mechanistic consequences of delaying Aβ aggregation via weak metal ion binding, quantitatively linking the contributions of specific interactions of metal ions with monomeric Aβ to their effects on bulk aggregation.
|
|
| 18. |
- Wärmländer, Sebastian, et al.
(författare)
-
Biophysical Studies of the Amyloid beta-Peptide : Interactions with Metal Ions and Small Molecules
- 2013
-
Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 14:14, s. 1692-1704
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is the most common of the protein misfolding (amyloid) diseases. The deposits in the brains of afflicted patients contain as a major fraction an aggregated insoluble form of the so-called amyloid beta-peptides (A beta peptides): fragments of the amyloid precursor protein of 39-43 residues in length. This review focuses on biophysical studies of the A beta peptides: that is, of the aggregation pathways and intermediates observed during aggregation, of the molecular structures observed along these pathways, and of the interactions of A beta with Cu and Zn ions and with small molecules that modify the aggregation pathways. Particular emphasis is placed on studies based on high-resolution and solid-state NMR methods. Theoretical studies relating to the interactions are also included. An emerging picture is that of A beta peptides in aqueous solution undergoing hydrophobic collapse together with identical partners. There then follows a relatively slow process leading to more ordered secondary and tertiary (quaternary) structures in the growing aggregates. These aggregates eventually assemble into elongated fibrils visible by electron microscopy. Small molecules or metal ions that interfere with the aggregation processes give rise to a variety of aggregation products that may be studied in vitro and considered in relation to observations in cell cultures or in vivo. Although the heterogeneous nature of the processes makes detailed structural studies difficult, knowledge and understanding of the underlying physical chemistry might provide a basis for future therapeutic strategies against the disease. A final part of the review deals with the interactions that may occur between the A beta peptides and the prion protein, where the latter is involved in other protein misfolding diseases.
|
|
| 19. |
- Åberg, Anna, et al.
(författare)
-
Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
-
Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
-
Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
|
|
