| 1. |
- Ahlstrand, Emma, et al.
(författare)
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Interaction energies between metal ions (Zn2+ and Cd2+) and biologically relevant ligands
- 2013
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Ingår i: International Journal of Quantum Chemistry. - Hoboken, NJ : Wiley. - 0020-7608 .- 1097-461X. ; 113:23, s. 2554-2562
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between the group XII metals Zn2+ and Cd2+ and amino acid residues play an important role in biology due to the prevalence of the first and the toxicity of the second. Estimates of the interaction energies between the ions and relevant residues in proteins are however difficult to obtain. This study reports on calculated interaction energy curves for small complexes of Zn2+ or Cd2+ and amino acid mimics (acetate, methanethiolate, and imidazole) or water. Given that many applications and models (e.g., force fields, solvation models, etc.) begin with and rely on an accurate description of gas-phase interaction energies, this is where our focus lies in this study. Four density functional theory (DFT)-functionals and MP2 were used to calculate the interaction energies not only at the respective equilibrium distances but also at a relevant range of ion–ligand separation distances. The calculated values were compared with those obtained by CCSD(T). All DFT-methods are found to overestimate the magnitude of the interaction energy compared to the CCSD(T) reference values. The deviation was analyzed in terms of energy components from localized molecular orbital energy decomposition analysis scheme and is mostly attributed to overestimation of the polarization energy. MP2 shows good agreement with CCSD(T) [root mean square error (RMSE) = 1.2 kcal/mol] for the eight studied complexes at equilibrium distance. Dispersion energy differences at longer separation give rise to increased deviations between MP2 and CCSD(T) (RMSE = 6.4 kcal/mol at 3.0 Å). Overall, the results call for caution in applying DFT methods to metalloprotein model complexes even with closed-shell metal ions such as Zn2+ and Cd2+, in particular at ion–ligand separations that are longer than the equilibrium distances.
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| 2. |
- Ahlstrand, Emma, et al.
(författare)
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Interaction Energies in Complexes of Zn and Amino Acids : A Comparison of Ab Initio and Force Field Based Calculations
- 2017
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 121:13, s. 2643-2654
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Tidskriftsartikel (refereegranskat)abstract
- Zinc plays important roles in structural stabilization of proteins, eniyine catalysis, and signal transduction. Many Zn binding sites are located at the interface between the protein and the cellular fluid. In aqueous solutions, Zn ions adopt an octahedral coordination, while in proteins zinc can have different coordinations, with a tetrahedral conformation found most frequently. The dynainics of Zn binding to proteins and the formation of complexes that involve Zn are dictated by interactions between Zn and its binding partners. We calculated the interaction energies between Zn and its ligands in complexes that mimic protein binding sites and in Zn complexes of water and one or two amino acid moieties, using quantum mechanics (QM) and molecular mechanics (MM). It was found that MM calculations that neglect or only approximate polarizability did not reproduce even the relative order of the QM interaction energies in these complexes. Interaction energies calculated with the CHARMM-Diode polarizable force field agreed better with the ab initio results,:although the deviations between QM and MM were still rather large (40-96 kcallmol). In order to gain further insight into Zn ligand interactions, the free energies of interaction were estimated by QM calculations with continuum solvent representation, and we performed energy decomposition analysis calculations to examine the characteristics of the different complexes. The ligand-types were found to have high impact on the relative strength of polarization and electrostatic interactions. Interestingly, ligand ligand interactions did not play a significant role in the binding of Zn. Finally) analysis of ligand exchange energies suggests that carboxylates could be exchanged with water molecules, which explains the flexibility in Zn:binding dynamics. An exchange between earboxylate (Asp/Glii) and imidazole (His) is less likely.
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| 3. |
- Alm, Jens, 1982-, et al.
(författare)
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Är barn en del av det planerande kollektivet : En studie om inkludering av barn i planering av kollektivtrafik
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet i denna rapport är att undersöka om och hur barn involveras i den regionala kollektivtrafikplaneringen. De vägledande frågorna för rapporten är följande:Hur har barnkonventionen påverkat arbetet i de regionala kollektivtrafikmyndigheterna?På vilka sätt och i vilka sammanhang inkluderas barn i kollektivtrafikplaneringen?Vilka hinder och möjligheter finns för att involvera barn i kollektivtrafikplaneringen?Projektet inleddes med en litteraturstudie för att kartlägga det rådande internationella och nationella kunskapsläget i frågan om barn i kollektivtrafikplanering och, eftersom studier på specifikt det ämnet var ytterligt få, i samhällsplanering i stort. I ett andra skede av projektet genomfördes dels e-postenkäter och studier av 21 trafikförsörjningsprogram och andra relevanta dokument, dels sju semi-strukturerade intervjuer med tjänstepersoner på sex olika regionala kollektivtrafikmyndigheter.Sammanfattningsvis illustrerar projektet att barnkonventionens implementering i den svenska lagstiftningen inte inneburit större förändringar hos svenska regionala kollektivtrafikmyndigheter i det korta perspektiv som vi studerat. Detta på grund av flertalet orsaker: bristande stöd och vägledning från nationella myndigheter, politiska mål för kollektivtrafiken som inte inkluderar barn, barnperspektiv i planeringen som inte utvecklas till att också inkludera barnen.Projektet har bidragit med ny kunskap om barns mobilitet i relation till kollektivtrafiken.En viktig slutsats är att skoltrafik och linjelagd trafik är tätt sammanbundna ur ett barnsmobilitetsperspektiv och att planeringen av dessa därför också bör vara sammankoppladeför att ett barnrättsperspektiv i kollektivtrafiken på allvar ska kunna uppnås. Detta kräverkommunal och regional samordning, inte bara av trafikplaneringen, utan ocksåsamhällsplanering, så att barnens målpunkter kan vara försörjda av kollektivtrafik,särskild eller linjelagd.
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| 4. |
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| 5. |
- Busayavalasa, Kiran, et al.
(författare)
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Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins
- 2020
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Ingår i: Plos Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- TheC.elegansproteins PAQR-2 (a homolog of the human seven-transmembrane domain AdipoR1 and AdipoR2 proteins) and IGLR-2 (a homolog of the mammalian LRIG proteins characterized by a single transmembrane domain and the presence of immunoglobulin domains and leucine-rich repeats in their extracellular portion) form a complex that protects against plasma membrane rigidification by promoting the expression of fatty acid desaturases and the incorporation of polyunsaturated fatty acids into phospholipids, hence increasing membrane fluidity. In the present study, we leveraged a novel gain-of-function allele of PAQR-1, a PAQR-2 paralog, to carry out structure-function studies. We found that the transmembrane domains of PAQR-2 are responsible for its functional requirement for IGLR-2, that PAQR-1 does not require IGLR-2 but acts via the same pathway as PAQR-2, and that the divergent N-terminal cytoplasmic domains of the PAQR-1 and PAQR-2 proteins serve a regulatory function and may regulate access to the catalytic site of these proteins. We also show that overexpression of human AdipoR1 or AdipoR2 alone is sufficient to confer increased palmitic acid resistance in HEK293 cells, and thus act in a manner analogous to the PAQR-1 gain-of-function allele. Author summary Cells are enclosed within membranes primarily composed of fat. When membranes contain much saturated fats, they tend to become more rigid, as with butter. Conversely, when membranes are rich in unsaturated fats, they become more fluid, as with vegetable oils. Our goal is to better understand how cells monitor and adjust the composition and properties of their membranes. We focus on a small group of proteins found in all animals, and called AdipoR1 and AdipoR2 in humans, and PAQR-1 and PAQR-2 in the wormCaenorhabditis elegans. We now found a version of PAQR-1 that is more "active", and promotes increased levels of unsaturated fats in membranes. By swapping different parts of the PAQR-1 protein with those of PAQR-2, we were able to determine which protein parts played which roles. We found that it is the transmembrane domains of PAQR-2 that dictate its requirements for another protein called IGLR-2 and that the intracellular domains of PAQR-1 and PAQR-2 play a regulatory role. These studies help understand how AdipoR1 and AdipoR2 regulate membrane composition in human cells, which is a vital function for us to thrive on diets that vary greatly in the types of fats that they contain.
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| 6. |
- Norén, Paulina, 1987-, et al.
(författare)
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Psychometric evaluation of the WHODAS 2.0 and prevalence of disability in a Swedish general population
- 2023
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Ingår i: Journal of Patient-Reported Outcomes. - : Springer. - 2509-8020. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The World Health Organization Disability Assessment Schedule (WHODAS 2.0) is a generic questionnaire that captures health and disability-related functioning information corresponding to six major life domains: Cognition, Mobility, Self-care, Getting along, Life activities, and Participation. The WHODAS 2.0 is used in a wide range of international clinical and research settings. A psychometric evaluation of WHODAS 2.0, Swedish version, in the general population is lacking, together with national reference data to enable interpretation and comparison. This study aims to evaluate the psychometric properties of the Swedish 36-item version of WHODAS 2.0 and describe the prevalence of disability in a Swedish general population.METHODS: A cross-sectional survey was performed. Internal consistency reliability was assessed with Cronbach's alpha. The construct validity was evaluated with item-total correlation, Pearson's correlation between the WHODAS 2.0 domains and the RAND-36 subscales, analysis of known groups by one-way ANOVA, and analysis of the factor structure by confirmatory factor analysis.RESULTS: Three thousand four hundred and eighty two adults aged 19-103 years (response rate 43%) participated. Significantly higher degrees of disability were reported by the oldest age group (≥ 80 years), adults with a low level of education, and those on sick leave. Cronbach's alpha was from 0.84 to 0.95 for the domain scores and 0.97 for the total score. The item-scale convergent validity was satisfactory, and the item-scale discriminant validity was acceptable except for the item about sexual activity. The data partially supported the factor structure, with borderline fit indices.CONCLUSION: The psychometric properties of the self-administered Swedish 36-item version of the WHODAS 2.0 are comparable to those of other language versions of the instrument. Data of the prevalence of disability in Swedish general population enables normative comparisons of WHODAS 2.0 scores of individuals and groups within clinical practice. The instrument has certain limitations that could be improved on in a future revision. The test-retest reliability and responsiveness of the Swedish version of WHODAS 2.0 for different somatic patient populations remain to be evaluated.
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| 7. |
- Philipson, Anna, 1978-, et al.
(författare)
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Mapping the World Health Organization Disability Assessment Schedule (WHODAS 2.0) onto SF-6D Using Swedish General Population Data
- 2023
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Ingår i: PharmacoEconomics - open. - : Springer Nature. - 2509-4262 .- 2509-4254. ; 7:5, s. 765-776
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Mapping algorithms can be used for estimating quality-adjusted life years (QALYs) when studies apply non-preference-based instruments. In this study, we estimate a regression-based algorithm for mapping between the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the preference-based instrument SF-6D to obtain preference estimates usable in health economic evaluations. This was done separately for the working and non-working populations, as WHODAS 2.0 discriminates between these groups when estimating scores.METHODS: Using a dataset including 2258 participants from the general Swedish population, we estimated the statistical relationship between SF-6D and WHODAS 2.0. We applied three regression methods, i.e., ordinary least squares (OLS), generalized linear models (GLM), and Tobit, in mapping onto SF-6D from WHODAS 2.0 at the overall-score and domain levels. Root mean squared error (RMSE) and mean absolute error (MAE) were used for validation of the models; R2 was used to assess model fit.RESULTS: The best-performing models for both the working and non-working populations were GLM models with RMSE ranging from 0.084 to 0.088, MAE ranging from 0.068 to 0.071, and R2 ranging from 0.503 to 0.608. When mapping from the WHODAS 2.0 overall score, the preferred model also included sex for both the working and non-working populations. When mapping from the WHODAS 2.0 domain level, the preferred model for the working population included the domains mobility, household activities, work/study activities, and sex. For the non-working population, the domain-level model included the domains mobility, household activities, participation, and education.CONCLUSIONS: It is possible to apply the derived mapping algorithms for health economic evaluations in studies using WHODAS 2.0. As conceptual overlap is incomplete, we recommend using the domain-based algorithms over the overall score. Different algorithms must be applied depending on whether the population is working or non-working, due to the characteristics of WHODAS 2.0.
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| 8. |
- Westerling, Ulrika, 1970-, et al.
(författare)
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In safe hands : a qualitative study on older adults' experiences of a tailored primary health care unit
- 2022
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 40:2, s. 271-280
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Today's health care system faces challenges in meeting the needs of older people with multimorbidity. To better cope with these needs, tailored primary health care with geriatric competence and person-centred care has been suggested. The aim of this study was to explore older patients' experiences of a tailored primary health care unit.Design: This was a qualitative study using semi-structured individual interviews and qualitative content analysis.Setting and patients: Nineteen patients were recruited from a tailored PHC unit for people aged 75 years or older in a region in central Sweden.Methods: The interview data were analysed using inductive category development.Results: In the analysis, the theme In safe hands when in need of primary health care emerged. The interviewees expressed a desire to participate in their own care. Easy access, enough consultation time and a calm environment, along with the PHC professionals' welcoming and attentive approach enhanced their feeling of being in safe hands. PHC professionals were perceived as having geriatric knowledge and taking responsibility for the care of older patients. Although the interviewees experienced that they received attention for their health conditions, a need for a more preventive approach to care emerged.Conclusion: Older patients highly appreciated their tailored PHC unit and they emphasised that it was an improvement compared to the ordinary PHC centre. This study provides insights into older patients' experiences, which may be helpful in the ongoing process of improving care for older patients in PHC.Older patients attending a tailored Primary health care (PHC) unit felt acknowledged, unlike in the ordinary PHC centre, which facilitated their participation in their care.The calm environment, specialist geriatric competence and ample patient contact time enabled them to feel secure and taken care of.Older patients expressed a need for an incorporation of social services and health promotion visits at the tailored PHC unit.
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| 9. |
- Westerling, Ulrika, 1970-, et al.
(författare)
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Informal caregivers' experiences of support from a tailored primary healthcare unit for older adults : A focus group study
- 2024
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Ingår i: Scandinavian Journal of Caring Sciences. - : Blackwell Publishing. - 0283-9318 .- 1471-6712.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Informal caregivers are an essential part of health and social care systems worldwide. As such, they may need professional support. AIM: The aim of this study was to describe informal caregivers' experiences and need for support from a tailored primary health care (PHC) unit.METHODS: This is a qualitative descriptive study using data collected from five semi-structured focus group discussions with a purposeful sample of 16 informal caregivers of older relatives. Respondents were recruited from a tailored PHC unit for people aged 75 years or older in a region in central Sweden. The data were analysed by qualitative content analysis with an abductive approach, based on the principles of the patient- and family-centred care framework.RESULTS: The overarching theme was 'Striving for partnership'. The findings indicate that informal caregivers to some extent felt supported by the healthcare professionals. However, the caregivers expressed a need to be further acknowledged by the professionals in order to participate in the care of their older relatives in the way they wanted. Moreover, insufficient information regarding the older adult's health condition and care provided by the professionals had a negative impact on the caregiver's participation in care.CONCLUSIONS: Informal caregivers have unmet needs for support and strive for a partnership with the PHC professionals. PHC professionals should be more attentive and invite informal caregivers to participate in the care of the older adult in order to meet their support needs and build an equal partnership. The patient- and family-centred care framework may be of guidance when providing care for older adults in a PHC context.
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