| 1. |
- Aad, G., et al.
(author)
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- 2016
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In: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 93:1
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Journal article (peer-reviewed)
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| 2. |
- Aad, G., et al.
(author)
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- 2015
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In: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; :12
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Journal article (peer-reviewed)
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| 3. |
- Aad, G., et al.
(author)
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- 2015
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In: Physical Review D. Particles and fields. - : American Physics Society. - 0556-2821 .- 1089-4918. ; 92:11
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Journal article (peer-reviewed)
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| 4. |
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| 5. |
- Griese, Julia J., et al.
(author)
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Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein
- 2013
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:43, s. 17189-17194
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Journal article (peer-reviewed)abstract
- Although metallocofactors are ubiquitous in enzyme catalysis, how metal binding specificity arises remains poorly understood, especially in the case of metals with similar primary ligand preferences such as manganese and iron. The biochemical selection of manganese over iron presents a particularly intricate problem because manganese is generally present in cells at a lower concentration than iron, while also having a lower predicted complex stability according to the Irving-Williams series (Mn-II < Fe-II < Ni-II < Co-II < Cu-II > Zn-II). Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein ligands in both metal sites self-assembles from MnII and FeII in vitro, thus diverging from the Irving-Williams series without requiring auxiliary factors such as metallochaperones. Crystallographic, spectroscopic, and computational data demonstrate that one of the two metal sites preferentially binds FeII over MnII as expected, whereas the other site is nonspecific, binding equal amounts of both metals in the absence of oxygen. Oxygen exposure results in further accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least a two-step process governed by both the intrinsic metal specificity of the protein scaffold and additional effects exerted during oxygen binding or activation. We further show that the mixed-metal cofactor catalyzes a two-electron oxidation of the protein scaffold, yielding a tyrosine-valine ether cross-link. Theoretical modeling of the reaction by density functional theory suggests a multistep mechanism including a valyl radical intermediate.
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| 6. |
- Roos, Elin, et al.
(author)
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Amyotrophic Lateral Sclerosis After Exposure to Manganese from Traditional Medicine Procedures in Kenya
- 2021
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In: Biological Trace Element Research. - : Springer Science and Business Media LLC. - 0163-4984 .- 1559-0720. ; 199, s. 3618-3624
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron loss and widespread muscular atrophy. Despite intensive investigations on genetic and environmental factors, the cause of ALS remains unknown. Recent data suggest a role for metal exposures in ALS causation. In this study we present a patient who developed ALS after a traditional medical procedure in Kenya. The procedure involved insertion of a black metal powder into several subcutaneous cuts in the lower back. Four months later, general muscle weakness developed. Clinical and electrophysiological examinations detected widespread denervation consistent with ALS. The patient died from respiratory failure less than a year after the procedure. Scanning electron microscopy and X-ray diffraction analyses identified the black powder as potassium permanganate (KMnO4). A causative relationship between the systemic exposure to KMnO4 and ALS development can be suspected, especially as manganese is a well-known neurotoxicant previously found to be elevated in cerebrospinal fluid from ALS patients. Manganese neurotoxicity and exposure routes conveying this toxicity deserve further attention.
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| 7. |
- Aaseth, Jan, et al.
(author)
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Treatment strategies in Alzheimers disease: a review with focus on selenium supplementation
- 2016
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In: Biometals. - : SPRINGER. - 0966-0844 .- 1572-8773. ; 29:5, s. 827-839
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Journal article (peer-reviewed)abstract
- Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.
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| 8. |
- Berntsson, Elina, et al.
(author)
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Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides : Effects on Aβ Structure and Aggregation
- 2023
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In: ACS Chemical Neuroscience. - 1948-7193. ; 14:15, s. 2618-2633
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Journal article (peer-reviewed)abstract
- Uranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions, including Alzheimer’s disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is the deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. The possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between Aβ peptides and uranyl ions, UO22+, of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. This suggests a possible link between AD and U exposure, which could be further explored by cell, animal, and epidemiological studies. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.
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| 9. |
- Berntsson, Elina, et al.
(author)
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Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation
- 2021
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In: Acta Biochimica Polonica. - : Polskie Towarzystwo Biochemiczne (Polish Biochemical Society). - 0001-527X .- 1734-154X. ; 68:2, s. 169-179
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is an incurable disease and the main cause of age-related dementia worldwide, despite decades of research. Treatment of AD with lithium (Li) has shown promising results, but the underlying mechanism is unclear. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. The plaques contain also metal ions of e.g. Cu, Fe, and Zn, and such ions are known to interact with Aβ peptides and modulate their aggregation and toxicity. The interactions between Aβ peptides and Li+ions have however not been well investigated. Here, we use a range of biophysical techniques to characterize in vitro interactions between Aβ peptides and Li+ions. We show that Li+ions display weak and non-specific interactions with Aβ peptides, and have minor effects on Aβ aggregation. These results indicate that possible beneficial effects of Li on AD pathology are not likely caused by direct interactions between Aβ peptides and Li+ions.
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| 10. |
- Berntsson, Elina, et al.
(author)
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Mercury Ion Binding to Apolipoprotein E Variants ApoE2, ApoE3, and ApoE4 : Similar Binding Affinities but Different Structure Induction Effects
- 2022
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In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:33, s. 28924-28931
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Journal article (peer-reviewed)abstract
- Mercury intoxication typically produces more severe outcomes in people with the APOE-ε4 gene, which codes for the ApoE4 variant of apolipoprotein E, compared to individuals with the APOE-ε2 and APOE-ε3 genes. Why the APOE-ε4 allele is a risk factor in mercury exposure remains unknown. One proposed possibility is that the ApoE protein could be involved in clearing of heavy metals, where the ApoE4 protein might perform this task worse than the ApoE2 and ApoE3 variants. Here, we used fluorescence and circular dichroism spectroscopies to characterize the in vitro interactions of the three different ApoE variants with Hg(I) and Hg(II) ions. Hg(I) ions displayed weak binding to all ApoE variants and induced virtually no structural changes. Thus, Hg(I) ions appear to have no biologically relevant interactions with the ApoE protein. Hg(II) ions displayed stronger and very similar binding affinities for all three ApoE isoforms, with KD values of 4.6 μM for ApoE2, 4.9 μM for ApoE3, and 4.3 μM for ApoE4. Binding of Hg(II) ions also induced changes in ApoE superhelicity, that is, altered coil–coil interactions, which might modify the protein function. As these structural changes were most pronounced in the ApoE4 protein, they could be related to the APOE-ε4 gene being a risk factor in mercury toxicity.
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| 11. |
- Berntsson, Elina, et al.
(author)
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Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides
- 2023
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD brains display deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-β (Aβ) peptides, and Aβ oligomers are likely a toxic species in AD pathology. AD patients display altered metal homeostasis, and AD plaques show elevated concentrations of metals such as Cu, Fe, and Zn. Yet, the metal chemistry in AD pathology remains unclear. Ni(II) ions are known to interact with Aβ peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods-mainly spectroscopy and imaging techniques-to characterize Aβ/Ni(II) interactions in vitro, for different Aβ variants: Aβ(1-40), Aβ(1-40)(H6A, H13A, H14A), Aβ(4-40), and Aβ(1-42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length Aβ monomers. Equimolar amounts of Ni(II) ions retard Aβ aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)·Aβ binding affinity is in the low µM range. The redox-active Ni(II) ions induce formation of dityrosine cross-links via redox chemistry, thereby creating covalent Aβ dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in Aβ monomers, while in a membrane-mimicking environment (SDS micelles) coil-coil helix interactions appear to be induced. For SDS-stabilized Aβ oligomers, Ni(II) ions direct the oligomers towards larger sizes and more diverse (heterogeneous) populations. All of these structural rearrangements may be relevant for the Aβ aggregation processes that are involved in AD brain pathology.
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| 12. |
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| 13. |
- Dahlgren, David, et al.
(author)
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Regional Intestinal Permeability of Three Model Drugs in Human
- 2016
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In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3013-3021
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Journal article (peer-reviewed)abstract
- Currently there are only a limited number of determinations of human P-eff in the distal small intestine and none in the large intestine. This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms. To meet this demand, three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers. The P-eff of each model drug was then calculated using a validated deconvolution method. The median P-eff of atenolol in the jejunum, ileum, and colon was 0.45, 0.15, and 0.013 X 10(-4) cm/s, respectively. The corresponding values for metoprolol were 1.72, 0.72, and 1.30 X 10(-4) cm/s, and for ketoprofen 8.85, 6.53, and 3.37 X 10(-4) cm/s, respectively. This is the first study where the human Peff of model drugs has been determined in all parts of the human intestinal tract in the same subjects. The jejunal values were similar to directly determined values using intestinal single-pass perfusion, indicating that the deconvolution method is a valid approach for determining regional P-eff. The values from this study will be highly useful in the validation of preclinical regional absorption models and in silico tools.
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| 14. |
- Gellein, Kristin, et al.
(author)
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Separation of proteins including metallothionein in cerebrospinal fluid by size exclusion HPLC and determination of trace elements by HR-ICP-MS
- 2007
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In: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1174, s. 136-142
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Journal article (peer-reviewed)abstract
- A method to study the protein binding patterns of trace elements in human cerebrospinal fluid (CSF) is described. Proteins in CSF samples were separated by size exclusion chromatography combined with high performance liquid chromatography (SEC-HPLC). The column was calibrated to separate proteins in the molecular weight range 6-70 kDa. Fractions were then analyzed off-line for trace elements using high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). We were able to accurately determine more than 10 elements of clinical interest in the CSF fractions. Results are presented for Cd, Mn, Fe, Pb, Cu and Zn. The total concentrations of 16 trace elements in human plasma and CSF are also presented. The method was able to differentiate the relative contribution of metallothionein and other proteins towards metal binding in human CSF.
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| 15. |
- Hammarström, Per, 1960-
(author)
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Nationens styvbarn : Judisk samhällsintegration i några Norrlandsstäder 1870-1940
- 2007
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In: Svensk kyrkotidning. - Stockholm : Carlsson Bokförlag. - 0346-2153. ; :51-52, s. 664-
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Doctoral thesis (other academic/artistic)abstract
- Syftet med denna avhandling är att undersöka vilken ekonomisk och social ställning den judiska minoriteten intog i det svenska samhället under perioden 1870 till 1940. Tidigare forskning har riktat stor uppmärksamhet mot rättsliga och politiska aspekter av den svenska judenhetens historia, mer sällan mot judarna och samhället i en bredare bemärkelse. Andra studier har lyft fram antisemitism på svensk mark utan att koppla fenomenet till en social nivå.Genom en undersökning av hur judiska invandrare, med ursprung i Östeuropa, successivt fogades in i några svenska lokalsamhällen, tar denna avhandling ett bredare grepp på frågan om judarna och samhället. Här undersöks hur den svenska judenheten integrerades i samhället efter det att emancipationen gett judarna fulla medborgerliga och politiska rättigheter. Judarnas ekonomiska och sociala ställning undersöks, liksom den sociala antisemitism som drabbade judarna. Studien rör sig i gränslandet mellan social- och kulturhistoria. Undersökningen visar att merparten av judarna i Sundsvall, en betydelsefull handelsstad i norra Sverige, fick sin försörjning genom en föga lönsam gårdfarihandel under början av undersökningsperioden. Sedan butiks- och grosshandelsrörelser började grundas inleddes en långsam socioekonomisk klättring. I takt med de ekonomiska framgångarna ökade judarnas sociala status, med engagemang i föreningslivet och lokalpolitiken. De framgångsrika familjerna tonade ner sin judiska identitet till förmån för en borgerlig och nationell kultur.Ungefär hälften av den judiska gruppen fick aldrig uppleva framgången utan förblev en marginaliserad grupp, med småhantverk eller gårdfarihandel som försörjningsbas. Det stora flertalet av denna underklass saknade svenskt medborgarskap. En social klyfta vidgades gentemot den judiska borgerligheten. Under hela undersökningsperioden var antisemitismen en kulturell kod i majoritetssamhället, oavsett integration och socioekonomisk framgång. Mycket tyder på att det sociala klimatet blev mer fientligt gentemot judarna efter 1920. Studien visar att nationalstaten Sverige lämnade litet utrymme för multikulturella strukturer. Judarna accepterades som nationens styvbarn men knappast som fullvärdiga svenskar.
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| 16. |
- Kjaer, Per, et al.
(author)
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GLA:D-(R) Back group-based patient education integrated with exercises to support self-management of back pain- development, theories and scientific evidence-
- 2018
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In: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 19
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Journal article (peer-reviewed)abstract
- BackgroundClinical guidelines recommend that people with back pain be given information and education about their back pain, advice to remain active and at work, and exercises to improve mobility and physical activity. Guidelines, however, rarely describe how this is best delivered. The aim of this paper is to present the development, theories, and underlying evidence for GLA:D Back - a group education and exercise program that translates guideline recommendations into a clinician-delivered program for the promotion of self-management in people with persistent/recurrent back pain.MethodsGLA:D Back, which included a rationale and objectives for the program, theory and evidence for the interventions, and program materials, was developed using an iterative process. The content of patient education and exercise programs tested in randomised trials was extracted and a multidisciplinary team of expert researchers and clinicians prioritised common elements hypothesised to improve back pain beliefs and management skills. The program was tested on eight people with persistent back pain in a university clinic and 152 patients from nine primary care physiotherapy and chiropractic clinics. Following feedback from the clinicians and patients involved, the working version of the program was created.ResultsEducational components included pain mechanisms, pain modulation, active coping strategies, imaging, physical activity, and exercise that emphasised a balance between the sum of demands and the individuals capacity. These were operationalised in PowerPoint presentations with supporting text to aid clinicians in delivering two one-hour patient education lectures.The exercise program included 16 supervised one-hour sessions over 8weeks, each comprising a warm-up section and eight types of exercises for general flexibility and strengthening of six different muscle groups at four levels of difficulty. The aims of the exercises were to improve overall back fitness and, at the same time, encourage patients to explore variations in movement by incorporating education content into the exercise sessions.ConclusionFrom current best evidence about prognostic factors in back pain and effective treatments for back pain, research and clinical experts developed a ready-to-use structured program - GLA:D (R) Back - to support self-management for people with persistent/recurrent back pain.
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| 17. |
- Koski, Lassi, et al.
(author)
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Metal ratios as possible biomarkers for amyotrophic lateral sclerosis
- 2023
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In: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 78
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Journal article (peer-reviewed)abstract
- Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown aetiology. Metals have been suspected to contribute to ALS pathogenesis since mid-19th century, yet studies on measured metal concentrations in ALS patients have often yielded conflicting results, with large individual variation in measured values. Calculating metal concentration ratios can unveil possible synergistic effects of neurotoxic metals in ALS pathogenesis. The aim of this study was to investigate if ratios of different metal concentrations in cerebrospinal fluid (CSF) and blood plasma, respectively, differ between ALS patients and healthy controls.Methods: Cerebrospinal fluid and blood plasma were collected from 17 ALS patients and 10 controls. Samples were analysed for 22 metals by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), and all possible 231 metal ratios calculated in each body fluid.Results: Fifty-three metal ratios were significantly elevated in ALS cases as compared to controls (p < 0.05); five in blood plasma, and 48 in CSF. The finding of fewer elevated ratios in blood plasma may indicate specific transport of metals into the central nervous system. The elevated metal ratios in CSF include Cd/Se (p = 0.031), and 16 ratios with magnesium, such as Mn/Mg (p = 0.005) and Al/Mg (p = 0.014).Conclusion: Metal ratios may be used as biomarkers in ALS diagnosis and as guidelines for preventive measures.
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| 18. |
- Koski, Lassi, et al.
(author)
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Metals in ALS TDP-43 Pathology
- 2021
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:22
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Research review (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these aggregation processes are currently unknown. In ALS, protein aggregation has been described for the SOD1, C9orf72, FUS and TDP-43 proteins. The latter is a nuclear protein normally binding to both DNA and RNA, contributing to gene expression and mRNA life cycle regulation. TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. ALS pathology appears to include metal imbalances, and environmental metal exposure is a known risk factor in ALS. However, studies on metal-to-TDP-43 interactions are scarce, even though this protein seems to have the capacity to bind to metals. This review discusses the possible role of metals in TDP-43 aggregation, with respect to ALS pathology.
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| 19. |
- Larsson, Susanna C., et al.
(author)
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Serum 25-hydroxyvitamin D in amyotrophic lateral sclerosis : mendelian randomization study
- 2020
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In: Neurobiology of Aging. - : ELSEVIER SCIENCE INC. - 0197-4580 .- 1558-1497. ; 87, s. 140.e1-140.e3
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Journal article (peer-reviewed)abstract
- We conducted a mendelian randomization study to investigate the association between serum 25-hydroxyvitamin D (S-25OHD) concentrations and amyotrophic lateral sclerosis (ALS). Summary-level data for genetic predictors of S-25OHD concentrations were acquired from 2 genome-wide association studies, comprising up to 79,366 individuals. The corresponding data for ALS were collected from 12,577 ALS cases and 23,475 controls. None of 7 single-nucleotide polymorphisms predicting S-25OHD concentrations was associated with ALS, and there was no overall association of genetic predisposition to higher S-25OHD concentrations with ALS. The odds ratio of ALS per genetically predicted one standard deviation increase of S-25OHD concentrations was 0.96 (95% confidence interval: 0.86-1.08; p = 0.52). We conclude that increasing S-25OHD concentrations will unlikely reduce ALS incidence.
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| 20. |
- Masso, H., et al.
(author)
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Ab initio characterization of C-5
- 2007
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 127:15
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Journal article (peer-reviewed)abstract
- In this paper, the structure and spectroscopic parameters of the C-5 cluster are determined using multiconfigurational quantum chemical methods as implemented in the MOLCAS software. A number of spectroscopic properties (band center positions, l-doubling parameters, and rotational constants) have been characterized. From the new results, the assignments of previous astrophysical observations [J. Goicoechea , Astrophys. J. 609, 225 (2004)] are discussed. A detailed exploration of the global potential energy surface confirms that C-5 has a X (1)Sigma(+)(g) linear isomer of prominent stability and, at least, three minimum energy structures showing singlet electronic ground states. Two of them are cyclic and one has a nonplanar geometry. Vertical and adiabatic electronic transitions and vibrational spectroscopic parameters are determined for the most stable linear isomer using multiconfigurational second order perturbation theory (CASPT2) using an active space containing 12 valence orbitals with 12 active electrons and extended ANO-type basis sets. The infrared spectrum has been analyzed from an anharmonic force field derived form the local surface, determined from the energies of a grid of 1350 geometries. The force field includes four coupling terms. The CASPT2 band center position of the nu(7)(pi(u)) anharmonic fundamental has been calculated to be at 102 cm(-1), which validates the assignment to C-5 of the pattern of bands centered at 102 cm(-1) observed with the ISO telescope. (C) 2007 American Institute of Physics.
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| 21. |
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| 22. |
- Persson, Lennart, et al.
(author)
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Density-dependent interactions in an Arctic char - brown trout system : competition, predation, or both?
- 2013
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In: Canadian Journal of Fisheries and Aquatic Sciences. - : Canadian Science Publishing. - 0706-652X .- 1205-7533. ; 70:4, s. 610-616
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Journal article (peer-reviewed)abstract
- In the study of mechanisms structuring fish communities, mixed competition-predation interactions where large predators feed on prey fish versus those in which small predators compete with prey fish for a shared prey have been the focus of substantial research. We used a long-term data set from a system inhabited by brown trout (Salmo trutta) (predator) and Arctic char (Salvelinus alpinus) (prey) to evaluate whether mixed interspecific interactions were present in this system as suggested in other studies focusing on this species pair. We found no evidence for a negative interspecific density dependence in individual performance in either Arctic char or brown trout. In contrast, a negative intraspecific density dependence was present, especially in Arctic char. Furthermore, large brown trout condition showed a positive response to encounter rate with Arctic char (related to the density of small Arctic char). The most parsimonious interaction module to explain the Arctic char - brown trout interaction patterns in the studied system does therefore not need to include interspecific competition. We suggest that size-structured mixed competition-predation interactions in different systems are realized as being either mainly structured through interspecific predation or by competition depending on species life history characteristics and environmental conditions.
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| 23. |
- Petersén, Åsa, et al.
(author)
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Orexin loss in Huntington's disease.
- 2005
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 14:1, s. 39-47
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Journal article (peer-reviewed)abstract
- Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. Mutant huntingtin forms intracellular aggregates and is associated with neuronal death in select brain regions. The most studied mouse model (R6/2) of HD replicates many features of the disease, but has been reported to exhibit only very little neuronal death. We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice. Importantly, we also found a significant atrophy and loss of orexin neurons in Huntington patients. Like animal models and patients with impaired orexin function, the R6/2 mice were narcoleptic. Both the number of orexin neurons in the lateral hypothalamus and the levels of orexin in the cerebrospinal fluid were reduced by 72% in end-stage R6/2 mice compared with wild-type littermates, suggesting that orexin could be used as a biomarker reflecting neurodegeneration. Our results show that the loss of orexin is a novel and potentially very important pathology in HD.
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| 24. |
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| 25. |
- Roos, Björn, et al.
(author)
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Theoretical characterization of the lowest-energy absorption band of pyrrole
- 2002
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 116:17, s. 7526-7536
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Journal article (peer-reviewed)abstract
- The lowest-energy band of the electronic spectrum of pyrrole has been studied with vibrational resolution by using multiconfigurational second-order perturbation theory (CASPT2) and its multistate extension (MS-CASPT2) in conjunction with large atomic natural orbital-type basis sets including Rydberg functions. The obtained results provide a consistent picture of the recorded spectrum in the energy region 5.5-6.5 eV and confirm that the bulk of the intensity of the band arises from a pipi(*) intravalence transition, in contradiction to recent theoretical claims. Computed band origins for the 3s,3p Rydberg electronic transitions are in agreement with the available experimental data, although new assignments are suggested. As illustrated in the paper, the proper treatment of the valence-Rydberg mixing is particularly challenging for ab initio methodologies and can be seen as the main source of deviation among the recent theoretical results as regards the position of the low-lying valence excited states of pyrrole. (C) 2002 American Institute of Physics.
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| 26. |
- Roos, Katarina, 1982-, et al.
(author)
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A comparison of two-electron chemistry performed by the manganese and iron heterodimer and homodimers
- 2012
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In: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 17:3, s. 363-373
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Journal article (peer-reviewed)abstract
- Two-electron chemistry with an iron dimer, a manganese dimer, and a manganese-iron dimer as a catalyst has been modeled using B3LYP* hybrid density functional theory. The recently discovered MnFe proteins form (at least) two functionally distinct groups, performing radical generation (class Ic ribonucleotide reductase subunit II) and substrate oxidations (subunit II-like ligand-binding oxidases, R2lox), respectively. Proteins from the latter group appear to be functionally similar to the diiron carboxylate proteins that perform two-electron oxidations of substrates, such as methane monooxygenase. To qualitatively determine the potential role of a MnFe center in R2lox, methane hydroxylation with the MnFe heterodimer and with the FeFe and MnMn homodimers is studied. The redox potential of the active state of the Mn(IV)Fe(IV) heterodimer is about 7 kcal mol(-1) lower than that of the active state of the Fe(IV)Fe(IV) homodimer, leading to a high barrier for the rate-limiting hydrogen abstraction with the MnFe site. If the entropy loss is not included, the barriers are lower, and the MnFe heterodimer can therefore have a role in R2lox as an oxidase for larger substrates exergonically bound to the protein. A MnMn center has a high barrier both with and without entropy loss. The higher stability of Fe(IV) in the presence of Mn(IV) in the other site compared with a second Fe(IV) suggests an explanation for the presence of the MnFe site in R2lox: to provide a metal center that is capable of two-electron chemistry, and which is more stable and less sensitive to external reductants than an Fe(IV)Fe(IV) site.
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| 27. |
- Roos, Katarina, et al.
(author)
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Activation of Dimanganese Class Ib Ribonucleotide Reductase by Hydrogen Peroxide : Mechanistic Insights from Density Functional Theory
- 2013
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In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 52:8, s. 4173-4184
-
Journal article (peer-reviewed)abstract
- Activation of manganese-dependent class Ib ribonucleotide reductase by hydrogen peroxide was modeled using B3LYP* hybrid density functional theory. Class Ib ribonucleotide reductase R2 subunit (R2F) does not react with molecular oxygen. Instead R2F is proposed to react with H2O2 or HO2-, provided by the unusual flavodoxin protein Nrdl, to generate the observed manganese(III) manganese(III) tyrosyl-radical state. On the basis of the calculations, an energetically feasible reaction mechanism is suggested for activation by H2O2, which proceeds through two reductive half-reactions. In the first reductive half-reaction, H2O2 is cleaved with a barrier of 13.1 kcal mol(-1) [Mn(II)Mn(II) -> Mn(III)Mn(III)], and in the second reductive half-reaction, H2O2 is cleaved with a barrier of 17.0 kcal mol(-1) [Mn(III)Mn(III) -> Mn(IV)Mn(IV)]. Tyrosyl-radical formation from both the Mn(IV)Mn(IV) state and a Mn(III)Mn(IV) state, where an electron and proton have been taken up, is both kinetically and thermodynamically accessible. Hence, chemically, H2O2 is a possible oxidant for the manganese-dependent R2F. The selectivity between the second reductive half-reaction and a competing oxidative reaction, as in manganese catalase, may be the time scale for the availability of H2O2. The role of Nrdl may be to provide H2O2 on the correct time scale.
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| 28. |
- Roos, Katarina, 1982-, et al.
(author)
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Density Functional Theory Study of the Manganese-Containing Ribonucleotide Reductase from Chlamydia trachomatis : Why Manganese Is Needed in the Active Complex
- 2009
-
In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 48:9, s. 1878-1887
-
Journal article (peer-reviewed)abstract
- The active center of Chlamydia trachomatis (Ct) ribonucleotide reductase (RNR) has been studied using B3LYP hybrid density functional theory. Class Ic Ct RNR lacks the radical-bearing tyrosine that is crucial for activity in conventional class I (subclass a and b) RNR. Instead of the Fe(III)Fe(III)Tyr(rad) active state in conventional class I, Ct RNR has Mn(IV)Fe(III) at the metal center of subunit H. Based on calculated (H+, e(-))-binding energies for Ct R2, iron-substituted Ct R2, and R2 from Escherichia coli (Ec), an explanation is proposed for why the enzyme needs this novel metal center. Mn(IV) is shown to be an equally strong oxidant as the tyrosyl radical in Ec R2. Fe(IV), however, is a much too strong oxidant and would therefore not be possible in the active cofactor. The structure of the catalytic center of the active state, such as protonation state and position of Mn, is discussed. Ct R2 has a different ligand structure than conventional class I R2 with a fourth Glu (like MMO) instead of three Glu and one Asp. Calculations indicate that, in the presence of Tyr, Glu at this position is less flexible than Asp, whereas with Phe both Glu and Asp are equally flexible. This may be a reason why conventional class I RNR has an Asp, while Ct R2, lacking the tyrosine, has a Glu.
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| 29. |
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| 30. |
- Roos, Katarina, 1982-, et al.
(author)
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Oxygen cleavage with manganese and iron in ribonucleotide reductase from Chlamydia trachomatis
- 2011
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In: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 16:4, s. 553-565
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Journal article (peer-reviewed)abstract
- The oxygen cleavage in Chlamydia trachomatis ribonucleotide reductase (RNR) has been studied using B3LYP* hybrid density functional theory. Class Ic C. trachomatis RNR lacks the radical-bearing tyrosine, crucial for activity in conventional class I (subclass a and b) RNR. Instead of the Fe(III)Fe(III)-Tyr(rad) active state, C. trachomatis RNR has a mixed Mn(IV)Fe(III) metal center in subunit II (R2). A mixed MnFe metal center has never been observed as a radical cofactor before. The active state is generated by reductive oxygen cleavage at the metal site. On the basis of calculated barriers for oxygen cleavage in C. trachomatis R2 and R2 from Escherichia coli with a diiron, a mixed manganese iron, and a dimanganese center, conclusions can be drawn about the effect of changing metals in R2. The oxygen cleavage is found to be governed by two factors: the redox potentials of the metals and the relative stability of the different peroxides. Mn(IV) has higher stability than Fe(IV), and the barrier is therefore lower with a mixed metal center than with a diiron center. With a dimanganese center, an asymmetric peroxide is more stable than the symmetric peroxide, and the barrier therefore becomes too high. Calculated proton-coupled redox potentials are compared to identify three possible R2 active states, the Fe(III)-Fe(III)-Tyr(rad) state, the Mn(IV)Fe(III) state, and. the Mn(IV)Mn(IV) state. A tentative energy profile of the thermodynamics of the radical transfer from R2 to subunit I is constructed to illustrate how the stability of the active states can be understood from a thermodynamical point of view.
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| 31. |
- Roos, Per M., et al.
(author)
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Manganese in cerebrospinal fluid and blood plasma of patients with amyotrophic lateral sclerosis
- 2012
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In: Experimental biology and medicine. - : SAGE Publications. - 1535-3702 .- 1535-3699. ; 237:7, s. 803-810
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Journal article (peer-reviewed)abstract
- Neurotoxic properties of manganese (Mn) are well documented. It is less known that Mn contributes to the development of neurodegenerative disorders in the general population. This study presents Mn data from patients with amyotrophic lateral sclerosis (ALS) in a well-defined cohort diagnosed by electrophysiological methods. Cerebrospinal fluid (CSF) and plasma were collected from patients and controls. Mn concentrations were analyzed by high-resolution inductively coupled plasma mass spectrometry. Concentrations of Mn were significantly higher in ALS CSF (median 5.67 mu g/L) than in CSF from controls (median 2.08 mu g/L). Also, ALS CSF Mn concentrations were higher than ALS plasma Mn concentrations (median 0.91 mu g/L), suggesting transport of Mn into the central nervous system. The properties of barrier systems between blood and the brain are discussed and the possibility of Mn accumulation contributing to the relentless course of ALS is introduced.
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| 32. |
- Roos, Per M, et al.
(author)
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Mercury in the Spinal Cord after Inhalation of Mercury
- 2012
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In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 111:2, s. 126-132
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) affects anterior horn cells of the spinal cord causing an indolent slow and steady deterioration of muscle strength leading inevitably to death in respiratory failure. ALS is a model condition for neurodegenerative disorders. Exposure to different agents dispersed in the environment has been suggested to cause neurodegeneration but no convincing evidence for such a link has yet been presented. Respiratory exposure to metallic mercury (Hg0) from different sources may be suspected. Body distribution of metallic mercury is fast and depends on solubility properties. Routes of transport, metabolism, excretion and biological half-life determine the overall toxic effects. Inhalation experiments were performed in 1984 where small marmoset monkeys (Callithrix jacchus) were exposed to 203Hg0 vapour mixed into the breathing air (4–5 μg/l). After 1 hr of exposure, they were killed and whole body autoradiograms prepared to study the distribution of mercury within organs. Autoradiograms showed that Hg was deposited inside the spinal cord. Areas of enhanced accumulation anatomically corresponding to motor nuclei could be observed. This study describes a reinvestigation, with new emphasis on the spinal cord, of these classical metal exposure data in a primate, focusing on their relevance for the causation of neurodegenerative disorders. A comparison with more recent rodent experiments with similar findings is included. The hypothesis that long-time low-dose respiratory exposure to metals, for example, Hg, contributes to neurodegenerative disorders is forwarded and discussed.
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| 33. |
- Roos, Per M., et al.
(author)
-
Metal Concentrations in Cerebrospinal Fluid and Blood Plasma from Patients with Amyotrophic Lateral Sclerosis
- 2013
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In: Biological Trace Element Research. - : Springer Science and Business Media LLC. - 0163-4984 .- 1559-0720. ; 151:2, s. 159-170
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.
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| 34. |
- Roos, Per M
(author)
-
Studies on metals in motor neuron disease
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- A slow but steady increase in neurodegenerative disorders has been noted in recent decades. Degenerations in the nervous system are found in Alzheimer's disease, Parkinson's disease and motor neuron diseases. Amyotrophic lateral sclerosis (ALS) is the most common of the motor neuron diseases. It is often considered a model disorder of neurodegeneration. Early symptoms of ALS are limb weakness or weakness in muscles of speech and swallowing. Muscle atrophy follow and a slowly progressing paralysis spreads to respiratory muscles invariably leading to death in respiratory failure. Neurophysiological investigations are necessary for proper diagnosis, and it is important to rule out treatable diagnostic alternatives such as myopathies or polyneuropathies. The cause of ALS is unknown. Prevailing theories include genetic, viral, inflammatory, oxidative or toxic mechanisms. Some indications point toward metallotoxic etiologies. Clusters of ALS have been observed in regions where geological conditions cause elevated metal concentrations in water and soil. Several studies show increased frequency of ALS in certain occupations. ALS-like conditions are found in animals, notably in horses, where metal exposure can be suspected. In addition animal metal exposure experiments show accumulations of metals in the spinal cord. The aim of this thesis project is to clarify the role of metals in ALS. The hypothesis tested is that neurotoxic metals contribute significantly to the pathogenesis of ALS. To study this we have measured concentrations of 22 metals in cerebrospinal fluid (CSF) and plasma from patients with ALS and from controls, and correlated findings to literature data to suggest a model for ALS pathogenesis. Increased concentrations were found for the metals manganese, aluminum, cadmium, cobalt, copper, zinc, lead, vanadium and uranium in CSF from patients with ALS compared to controls. Manganese showed the most prominent correlation. Simultaneous sampling from plasma did not show these elevated concentrations, indicating metal accumulations in ALS CSF. Most of the metals detected in CSF from ALS patients are neurotoxicants. Studies of mercury distribution in a monkey showed mercury accumulations in the spinal cord after respiratory exposure to mercury. Motor neurons of the spinal cord seem to be more vulnerable to metal toxicity then surrounding cells, as they lack protection from the metal-binding protein metallothionein. Patient exposure to metals, distribution by the bloodstream, penetration of protective barriers and direct toxic effects on neurons of the spinal cord is suggested to be causative in ALS. It is concluded that neurotoxic metals can reach and affect the anterior horn cells of motor neurons and thereby contribute to the pathogenesis of ALS.
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| 35. |
- Shafaat, Hannah S., et al.
(author)
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Electronic Structural Flexibility of Heterobimetallic Mn/Fe Cofactors : R2lox and R2c Proteins
- 2014
-
In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 136:38, s. 13399-13409
-
Journal article (peer-reviewed)abstract
- The electronic structure of the Mn/Fe cofactor identified in a new class of oxidases (R2lox) described by Andersson and Hogbom [Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 5633] is reported. The R2lox protein is homologous to the small subunit of class Ic ribonucleotide reductase (R2c) but has a completely different in vivo function. Using multifrequency EPR and related pulse techniques, it is shown that the cofactor of R2lox represents an antiferromagnetically coupled Mn-III/Fe-III dimer linked by a mu-hydroxo/bis-mu-carboxylato bridging network. The Mn-III ion is coordinated by a single water ligand. The R2lox cofactor is photoactive, converting into a second form (R2lox(photo)) upon visible illumination at cryogenic temperatures (77 K) that completely decays upon warming. This second, unstable form of the cofactor more closely resembles the Mn-III/Fe-III cofactor seen in R2c. It is shown that the two forms of the R2lox cofactor differ primarily in terms of the local site geometry and electronic state of the Mn-III ion, as best evidenced by a reorientation of its unique Mn-55 hyperfine axis. Analysis of the metal hyperfine tensors in combination with density functional theory (DFT) calculations suggests that this change is triggered by deprotonation of the mu-hydroxo bridge. These results have important consequences for the mixed-metal R2c cofactor and the divergent chemistry R2lox and R2c perform.
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| 36. |
- Wallin, Cecilia, et al.
(author)
-
Alzheimer's disease and cigarette smoke components : effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-beta peptide aggregation
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- Cigarette smoking is a significant risk factor for Alzheimer’s disease (AD), which is associated with extracellular brain deposits of amyloid plaques containing aggregated amyloid-β (Aβ) peptides. Aβ aggregation occurs via multiple pathways that can be influenced by various compounds. Here, we used AFM imaging and NMR, fluorescence, and mass spectrometry to monitor in vitro how Aβ aggregation is affected by the cigarette-related compounds nicotine, polycyclic aromatic hydrocarbons (PAHs) with one to five aromatic rings, and the metal ions Cd(II), Cr(III), Pb(II), and Pb(IV). All PAHs and metal ions modulated the Aβ aggregation process. Cd(II), Cr(III), and Pb(II) ions displayed general electrostatic interactions with Aβ, whereas Pb(IV) ions showed specific transient binding coordination to the N-terminal Aβ segment. Thus, Pb(IV) ions are especially prone to interact with Aβ and affect its aggregation. While Pb(IV) ions affected mainly Aβ dimer and trimer formation, hydrophobic toluene mainly affected formation of larger aggregates such as tetramers. The uncharged and hydrophilic nicotine molecule showed no direct interactions with Aβ, nor did it affect Aβ aggregation. Our Aβ interaction results suggest a molecular rationale for the higher AD prevalence among smokers, and indicate that certain forms of lead in particular may constitute an environmental risk factor for AD.
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| 37. |
- Wallin, Cecilia, et al.
(author)
-
Characterization of Mn(II) ion binding to the amyloid-beta peptide in Alzheimer's disease
- 2016
-
In: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 38, s. 183-193
-
Journal article (peer-reviewed)abstract
- Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-beta (A beta) peptides. Previous studies have shown that A beta displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate A beta aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the A beta(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to A beta may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying A beta binding reveals more complex AD metal chemistry than has been previously considered in the literature.
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| 38. |
- Wallin, Cecilia, et al.
(author)
-
Mercury and Alzheimer's Disease : Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization
- 2020
-
In: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:1
-
Journal article (peer-reviewed)abstract
- Brains and blood of Alzheimer's disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-beta (A beta) peptides aggregated into amyloid fibrils. A beta peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II). Here, we study in vitro the interactions between A beta peptides and Hg(II) ions by multiple biophysical techniques. Fluorescence spectroscopy and atomic force microscopy (AFM) show that Hg(II) ions have a concentration-dependent inhibiting effect on A beta fibrillization: at a 1:1 A betaHg(II) ratio only non-fibrillar A beta aggregates are formed. NMR spectroscopy shows that Hg(II) ions interact with the N-terminal region of A beta(1-40) with a micromolar affinity, likely via a binding mode similar to that for Cu(II) and Zn(II) ions, i.e., mainly via the histidine residues His6, His13, and His14. Thus, together with Cu(II), Fe(II), Mn(II), Pb(IV), and Zn(II) ions, Hg(II) belongs to a family of metal ions that display residue-specific binding interactions with A beta peptides and modulate their aggregation processes.
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| 39. |
- Wenzel, Michaela, 1986, et al.
(author)
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Control of septum thickness by the curvature of SepF polymers
- 2021
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:2
-
Journal article (peer-reviewed)abstract
- Gram-positive bacteria divide by forming a thick cross wall. How the thickness of this septal wall is controlled is unknown. In this type of bacteria, the key cell division protein FtsZ is anchored to the cell membrane by two proteins, FtsA and/or SepF. We have isolated SepF homologs from different bacterial species and found that they all polymerize into large protein rings with diameters varying from 19 to 44 nm. Interestingly, these values correlated well with the thickness of their septa. To test whether ring diameter determines septal thickness, we tried to construct different SepF chimeras with the purpose to manipulate the diameter of the SepF protein ring. This was indeed possible and confirmed that the conserved core domain of SepF regulates ring diameter. Importantly, when SepF chimeras with different diameters were expressed in the bacterial host Bacillus subtilis, the thickness of its septa changed accordingly. These results strongly support a model in which septal thickness is controlled by curved molecular clamps formed by SepF polymers attached to the leading edge of nascent septa. This also implies that the intrinsic shape of a protein polymer can function as a mold to shape the cell wall.
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| 40. |
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| 41. |
- Åström, Mats E., 1963-, et al.
(author)
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Geochemistry of multiple sclerosis in Finland
- 2022
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 841
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Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) affects some 3 million people around the world and the prevalence is increasing. The MS incidence increases with distance from the equator forming a north-to-south gradient. The cause of this gradient and the cause of MS in general are largely unknown. Sulphide-bearing marine and lake sediments, when exposed to oxygen after drainage, form sulphuric acid resulting in the development of acid sulphate soils. From these soils major neurotoxic metals such as iron, aluminum and manganese and trace metals such as nickel, copper and cadmium are released into the surrounding environment. As these soils are largely used for farming, obvious routes to human metal exposure exist. Here we compare the distribution of acid sulphate soils in Finland to the geographic localisation of MS cases using data from a national acid sulphate soil mapping project and historical MS distribution data. Finland has among the highest MS prevalences in the world and several independent nationwide surveys have shown the highest prevalence in western Finland, stable over time. Acid sulphate soil distribution colocalizes with MS, both on a regional (nationwide) scale and local (proximity to rivers) scale. A toxicokinetic LADME model for MS pathogenesis is presented. We propose that neurotoxic metals leaching from acid sulphate soils contribute to the clustering of MS in Finland.
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