| 1. |
- Allard, Christina, et al.
(author)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Other publication (pop. science, debate, etc.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Allen, Marie, et al.
(author)
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Association of susceptibility to multiple sclerosis in Sweden with HLA class II DRB1 and DQB1 alleles
- 1994
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In: Human Immunology. - 0198-8859 .- 1879-1166. ; 39:1, s. 41-8
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Journal article (peer-reviewed)abstract
- The association of MS with HLA class II alleles was studied by PCR-based typing of the DQA1, DQB1, DRB1, and DPB1 loci in 94 Swedish patients with relapses and remissions of the disease. The haplotype DRB1*1501-DQA1*0102-DQB1*0602 was found to be positively associated and three haplotypes were found to be negatively associated with MS. Linkage disequilibrium makes it difficult to assess whether DRB1 or DQB1 plays the primary role in the disease association, while the association with DPB1 and DQA1 appears to be secondary to that of DQB1 and DRB1. Two of the three haplotypes negatively associated with MS carry the DQB1*0301 allele. Also, the negatively associated DRB1*0401-DQA1*0301-DQB1*0301 haplotype differs from those with nonassociated DRB1*0401-DQA1*0301-DQB1*0302 haplotype only at DQB1. These results suggest that DQB1 alleles, as well as some DRB1 alleles, are involved in susceptibility and protection to MS. In searching for sequence motifs in the DR beta chain associated with MS susceptibility, all DRB1 alleles on haplotypes positively associated with MS, including the DRB1*1501, were found to encode a Val at position 86 of the DR beta chain. Also, DRB1 alleles that are negatively associated with MS all encode a Gly at position 86, suggesting that the residue at position 86 may be critical in conferring susceptibility and protection to MS. Finally, when the effect of the DRB1*1501 haplotype was removed there was no support for the hypothesis that MS is associated with a putative DQ-alpha beta heterodimer, encoded for by certain DQA1 and DQB1 alleles.
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| 6. |
- Allentoft, Morten E., et al.
(author)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Journal article (peer-reviewed)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 7. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 8. |
- Andersson, Niklas, 1970, et al.
(author)
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Investigation of central versus peripheral effects of estradiol in ovariectomized mice
- 2005
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In: J Endocrinol. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 187:2, s. 303-9
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Journal article (peer-reviewed)abstract
- It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.
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| 9. |
- Backman, Annica C., 1972-, et al.
(author)
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Exploring the impact of nursing home managers' leadership on staff job satisfaction, health and intention to leave in nursing homes
- 2023
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In: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702.
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Journal article (peer-reviewed)abstract
- Aims and ObjectivesTo explore the impact of nursing home leadership and staffing characteristics on staff job satisfaction, health and intention to leave. BackgroundThe number of older people has outpaced growth in the nursing home workforce worldwide. Identifying predictors with the potential to positively impact staff job satisfaction, health and intentions to leave are important. Leadership of the nursing home manager can be one such predictor. DesignCross-sectional design. MethodsA sample of 2985 direct care staff in 190 nursing homes in 43 randomly selected municipalities in Sweden completed surveys on leadership, job satisfaction, self-rated health and intention to leave (response rate 52%). Descriptive statistics and Generalised Estimating Equations were conducted. The STROBE reporting checklist was applied. ResultsNursing home managers' leadership was positively related to job satisfaction, self-rated health and low intention to leave. Lower staff educational levels were related to poorer health and lower job satisfaction. ConclusionsNursing home leadership plays a significant role in the job satisfaction, self-reported health and intention to leave of direct care staff. Low education levels among staff seem to negatively influence staff health and job satisfaction, suggesting that educational initiatives for less-educated staff could be beneficial for improving staff health and job satisfaction. Relevance to clinical practiceManagers seeking to improve staff job satisfaction can consider how they support, coach and provide feedback. Recognising staff achievement at work can contribute to high job satisfaction. One important implication for managers is to offer continuing education to staff with lower or no education, given the large amount of uneducated direct care workers in aged care and the impact this may have on staff job satisfaction and health. No patient or public contributionNo patient or public contribution was required to outcome measures in this study. Direct care staff and managers contributed with data.
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| 10. |
- Backman, Annica C., 1972-, et al.
(author)
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Longitudinal changes in nursing home leadership, direct care staff job strain and social support in Swedish nursing homes : findings from the U-AGE SWENIS study
- 2023
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In: International Journal of Older People Nursing. - : John Wiley & Sons. - 1748-3735 .- 1748-3743. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: Promoting healthy work environment as a manager in nursing homes is important to safeguard staff health and well-being as well as care quality when facing increasing demands. The impact of leadership on staff work environment needs further exploration.Objectives: To describe longitudinal changes in nursing home leadership, direct care staff characteristics, job strain and social support.Methods: This study has a repeated cross-sectional design, a five-year follow-up study. Nursing home staff in 181 corresponding units (n = 1253 in 2014 and n = 1176 in 2019) completed surveys about leadership, staff job strain and social support in a five-year follow-up study. Descriptive and regression analyses were conducted.Results: A higher degree of leadership defined by coaching and providing direct feedback to care staff, handling conflicts in a constructive way and having control of the clinical work, was significantly associated with a lower degree of job strain and a higher degree of social support among staff, with stronger associations at follow-up. The proportion of enrolled nurses increased significantly at follow-up.Conclusions: Leadership is increasingly important for staff work environment, especially in times of increased workload and decreasing collegiality and deteriorating work atmosphere at work. Implications for Practice: Stakeholder and policy makers in nursing home care may reflect on how managers' leadership is prioritised in these environments because such leadership is associated with staff job strain and social support. Managers striving to improve the work situation of staff may consider their own role and allow flexibility in how and when the work can be performed.
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| 11. |
- Backman, Annica C., 1972-, et al.
(author)
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The influence of nursing home managers’ leadership on person-centred care and stress of conscience: A cross-sectional study
- 2021
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In: BMC Nursing. - : BioMed Central. - 1472-6955. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Leadership and stress are common concepts in nursing, and this study explores empirically the connection between leadership and stress of conscience in the context of aged care practice. Previous literature has shown that when staff are unable to carry out their ethical liabilities towards the residents, feelings of guilt may occur among staff, which may be an expression of stress of conscience. Although leadership has been described as crucial for staff’s work perceptions of stress as well as for person-centred practices, the influence of nursing home managers’ leadership on stress of conscience among staff and person-centred practices is still not fully explored. This study attempts to address that knowledge gap by exploring the relationship between leadership, person-centred care, and stress of conscience.Methods: This study was based on a cross-sectional national survey of 2985 staff and their managers in 190 nursing homes throughout Sweden. Descriptive statistics and regression modelling were used to explore associations.Results: Leadership was associated with a higher degree of person-centred care and less stress of conscience. A higher degree of person-centred care was also associated with less stress of conscience. The results also showed that leadership as well as person-centred care were individually associated with lower levels of stress of conscience when adjusting for potential confounders.Conclusion: Nursing home managers’ leadership was significantly associated with less staff stress of conscience and more person-centred care. This indicates that a leadership most prominently characterised by coaching and giving feedback, relying on staff and handling conflicts constructively, experimenting with new ideas, and controlling work individually can contribute to less staff stress as well as higher degree of person-centred care provision.
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| 12. |
- Backman, Annica C., 1972-, et al.
(author)
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The significance of nursing home managers' leadership : longitudinal changes, characteristics and qualifications for perceived leadership, person-centredness and climate
- 2022
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In: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 31:9-10, s. 1377-1388
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Journal article (peer-reviewed)abstract
- Aims and objectives: The aim was to explore changes in nursing home managers' leadership, person-centred care and psychosocial climate comparing matched units in a five-year follow-up and to explore the significance of managers' educational qualifications and the ownership of nursing homes for perceived leadership, person-centred care and psychosocial climate in the follow-up data.Background: Leadership has been described as crucial for person-centred care and psychosocial climate even though longitudinal data are lacking. The significance of managerial leadership, its characteristics, managerial qualifications and ownership of nursing homes for perceived leadership, person-centred care and psychosocial climate also needs further exploration.Design: Repeated cross-sectional study.Methods: This study used valid and reliable measures of leadership, person-centred care, psychosocial climate and demographic variables collected from managers and staff n = 3605 in 2014 and n = 2985 in 2019. Descriptive and regression analyses were used. The STROBE checklist was used in reporting this study.Results: Leadership was still positively significantly associated to person-centred care in a five-year follow-up, but no changes in strength were seen. Leadership was still positively significantly associated with psychosocial climate, with stronger associations at follow-up. Six leadership characteristics increased over time. It was also shown that a targeted education for nursing home managers was positively associated with person-centred care.Conclusions: Leadership is still pivotal for person-centred care and psychosocial climate. Knowledge of nursing home managers' leadership, characteristics and educational qualifications of significance for person-centred delivery provides important insights when striving to improve such services.Relevance to clinical practice: The findings can be used for management and clinical practice development initiatives because it was shown that nursing home managers' leadership is vital to person-centred care practices and improves the climate for both staff and residents in these environments.
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| 13. |
- Backman, Annica, et al.
(author)
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Characteristics of highly rated leadership in nursing homes using item response theory
- 2017
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In: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648. ; 73:12, s. 2903-2913
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Journal article (peer-reviewed)abstract
- Aim: To identify characteristics of highly rated leadership in nursing homes. Background: An ageing population entails fundamental social, economic and organizational challenges for future aged care. Knowledge is limited of both specific leadership behaviours and organizational and managerial characteristics which have an impact on the leadership of contemporary nursing home care. Design: Cross-sectional. Method: From 290 municipalities, 60 were randomly selected and 35 agreed to participate, providing a sample of 3605 direct-care staff employed in 169 Swedish nursing homes. The staff assessed their managers' (n = 191) leadership behaviours using the Leadership Behaviour Questionnaire. Data were collected from November 2013 - September 2014, and the study was completed in November 2016. A two-parameter item response theory approach and regression analyses were used to identify specific characteristics of highly rated leadership. Results: Five specific behaviours of highly rated nursing home leadership were identified; that the manager: experiments with new ideas; controls work closely; relies on subordinates; coaches and gives direct feedback; and handles conflicts constructively. The regression analyses revealed that managers with social work backgrounds and privately run homes were significantly associated with higher leadership ratings. Conclusion: This study highlights the five most important leadership behaviours that characterize those nursing home managers rated highest in terms of leadership. Managers in privately run nursing homes and managers with social work backgrounds were associated with higher leadership ratings. Further work is needed to explore these behaviours and factors predictive of higher leadership ratings.
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| 14. |
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| 15. |
- Backman, Annica, et al.
(author)
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Towards person-centredness in aged-care : exploring the impact of leadership
- 2016
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In: Journal of Nursing Management. - : Hindawi Limited. - 0966-0429 .- 1365-2834. ; 24:6, s. 766-774
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Journal article (peer-reviewed)abstract
- Aim: To explore the association between leadership behaviours among managers in aged care, and person‐centredness of care and the psychosocial climate.Background: Theory suggests that leadership is important for improving person‐centredness in aged care, however, empirical evidence is lacking.Methods: A cross‐sectional design was used to collect data from Swedish aged care staff (n = 3661). Valid and reliable questionnaires assessing leadership behaviours, person‐centeredness of care and the psychosocial climate were used. Data were analysed using multiple linear regression including interaction terms.Results: Leadership behaviours were significantly related to the person‐centredness of care and the psychosocial climate. The level of person‐centredness of care moderated the impact of leadership on the psychosocial climate.Conclusions and implications for nursing management: The leadership behaviour of managers significantly impacts person‐centred care practice and contributes to the psychosocial climate for both staff and residents in aged care. This study is the first empirically to confirm that middle managers have a central leadership role in developing and supporting person‐centred care practice, thereby creating a positive psychosocial climate and high quality care.
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| 16. |
- Baxter, Rebecca, et al.
(author)
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The thriving of older people assessment scale : Psychometric evaluation and short‐form development
- 2019
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In: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 75:12, s. 3831-3843
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Journal article (peer-reviewed)abstract
- Aim: To evaluate the psychometric properties and performance of the 32‐item Thriving of Older People Assessment Scale (TOPAS) and to explore reduction into a short‐form.Background: The 32‐item TOPAS has been used in studies of place‐related well‐being as a positive measure in long‐term care to assess nursing home resident thriving; however, item redundancy has not previously been explored.Design: Cross‐sectional.Method: Staff members completed the 32‐item TOPAS as proxy‐raters for a random sample of Swedish nursing home residents (N = 4,831) between November 2013 and September 2014. Reliability analysis, exploratory factor analysis and item response theory‐based analysis were undertaken. Items were systematically identified for reduction using statistical and theoretical analysis. Correlation testing, means comparison and model fit evaluation confirmed scale equivalence.Results: Psychometric properties of the 32‐item TOPAS were satisfactory and several items were identified for scale reduction. The proposed short‐form TOPAS exhibited a high level of internal consistency (α=0.90) and strong correlation (r=0.98) to the original scale, while also retaining diversity among items in terms of factor structure and item difficulties.Conclusion: The 32‐item and short‐form TOPAS' indicated sound validity and reliability to measure resident thriving in the nursing home context.Impact: There is a lack of positive life‐world measures for use in nursing homes. The short‐form TOPAS indicated sound validity and reliability to measure resident thriving, providing a feasible measure with enhanced functionality for use in aged care research, assessments and care planning for health promoting purposes in nursing homes.
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| 17. |
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| 18. |
- Betancourt, Lazaro Hiram, et al.
(author)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Journal article (peer-reviewed)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 19. |
- Börjesson, Anna E, et al.
(author)
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Roles of transactivating functions 1 and 2 of estrogen receptor-alpha in bone.
- 2011
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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. ; 108:15, s. 6288-6293
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Journal article (peer-reviewed)abstract
- The bone-sparing effect of estrogen is primarily mediated via estrogen receptor-α (ERα), which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand binding domain. To evaluate the role of ERα AF-1 and ERα AF-2 for the effects of estrogen in bone in vivo, we analyzed mouse models lacking the entire ERα protein (ERα(-/-)), ERα AF-1 (ERαAF-1(0)), or ERα AF-2 (ERαAF-2(0)). Estradiol (E2) treatment increased the amount of both trabecular and cortical bone in ovariectomized (OVX) WT mice. Neither the trabecular nor the cortical bone responded to E2 treatment in OVX ERα(-/-) or OVX ERαAF-2(0) mice. OVX ERαAF-1(0) mice displayed a normal E2 response in cortical bone but no E2 response in trabecular bone. Although E2 treatment increased the uterine and liver weights and reduced the thymus weight in OVX WT mice, no effect was seen on these parameters in OVX ERα(-/-) or OVX ERαAF-2(0) mice. The effect of E2 in OVX ERαAF-1(0) mice was tissue-dependent, with no or weak E2 response on thymus and uterine weights but a normal response on liver weight. In conclusion, ERα AF-2 is required for the estrogenic effects on all parameters evaluated, whereas the role of ERα AF-1 is tissue-specific, with a crucial role in trabecular bone and uterus but not cortical bone. Selective ER modulators stimulating ERα with minimal activation of ERα AF-1 could retain beneficial actions in cortical bone, constituting 80% of the skeleton, while minimizing effects on reproductive organs.
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| 20. |
- Börjesson, Anna E, et al.
(author)
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SERMs have substance-specific effects on bone, and these effects are mediated via ER alpha AF-1 in female mice
- 2016
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 310:11
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Journal article (peer-reviewed)abstract
- The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)alpha, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ER alpha AF-1 for the estradiol (E-2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ER alpha AF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ER alpha AF-1 (ER alpha AF-1(0)) with E-2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ER alpha AF-1(0) mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ER alpha AF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis.
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| 21. |
- Börjesson, Anna E, et al.
(author)
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The role of activation functions 1 and 2 of estrogen receptor-alpha for the effects of estradiol and selective estrogen receptor modulators in male mice
- 2013
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 28:5, s. 1117-1126
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Journal article (peer-reviewed)abstract
- Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ER had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ER for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERAF-1 (ERAF-10), ERAF-2 (ERAF-20), or the total ER (ER/) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ER/ or ERAF-20 mirx ERAF-10 mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERAF-1 for the effects of SERMs, we treated orx WT and ERAF-10 mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERAF-10 mice. In conclusion, ERAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERAF-1. Our findings might contribute to the development of bone-specific SERMs in males. (c) 2013 American Society for Bone and Mineral Research.
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| 22. |
- Börjesson, Anna E, et al.
(author)
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The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
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In: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
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Journal article (peer-reviewed)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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| 23. |
- Corneliusson, Laura, et al.
(author)
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Well‐being and Thriving in Sheltered Housing versus Ageing in Place : Results from the U‐Age Sheltered Housing Study
- 2020
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In: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648. ; 73:3, s. 856-866
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Journal article (peer-reviewed)abstract
- Aims: To explore to what extent type of residence (sheltered housing or ageing in place) contributes to thriving and well-being in older adults, when controlling for age, sex, living alone, being a widow and adjusting for functional status, self-rated health, and depressive mood.Design: A matched cohort study.Methods A self-report survey was sent out to a total population of residents in all sheltered housings in Sweden and a matched control group ageing in place (N = 3,805). The data collection took place between October 2016-January 2017.Results: The interaction analyses related to thriving showed that with increasing level of depressive mood and decreasing levels of self-rated health and functional status, those residing in sheltered housing generally reported higher levels of thriving, as compared with those ageing in place. Well-being was not found to be significantly associated with type of accommodation.Conclusion: There may be features in sheltered housing that are associated with resident thriving especially among individuals with impairments of function, health or mood, although further studies are required to identify these specific features.Impact: This study informs staff and policymakers about thriving and well-being in sheltered housing accommodations. These findings may be used to further the development of sheltered housing accommodations.
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| 24. |
- Dickson, Elna, et al.
(author)
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Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease
- 2023
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In: Journal of Huntington's disease. - 1879-6397. ; 12:3, s. 253-266
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Journal article (peer-reviewed)abstract
- BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake in adipocytes from gonadal WAT was assessed.RESULTS: In R6/2 mice, WAT depot weights were comparable to wildtype (WT) mice, and the response to insulin and isoprenaline in gonadal adipocytes was unaltered. Leptin-deficient R6/2 mice exhibited distinct changes compared to leptin-deficient WT mice. At 12 weeks, female leptin-deficient R6/2 mice had reduced body weight accompanied by an increased proportion of smaller adipocytes, while in contrast; male mice displayed a shift towards larger adipocyte sizes without a significant body weight reduction at this timepoint.CONCLUSIONS: We here show that there are early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 mice and leptin-deficient R6/2 mice.
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| 25. |
- Dong, Jin, et al.
(author)
-
Understanding Statin-Roxadustat Drug–Drug-Disease Interaction Using Physiologically-Based Pharmacokinetic Modeling
- 2023
-
In: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 114:4, s. 825-835
-
Journal article (peer-reviewed)abstract
- A different drug–drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HVs), depending on the interplay between drug–drug and disease (drug-drug-disease interaction (DDDI)). Physiologically-based pharmacokinetic (PBPK) modeling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modeling in the severe CKD population is still low when nonrenal pathways are involved. More mechanistic virtual disease population and robust validation cases are needed. To this end, we aimed to: (i) understand the implications of severe CKD on statins (atorvastatin, simvastatin, and rosuvastatin) pharmacokinetics (PK) and DDI; and (ii) predict untested clinical scenarios of statin-roxadustat DDI risks in patients to guide suitable dose regimens. A novel virtual severe CKD population was developed incorporating the disease effect on both renal and nonrenal pathways. Drug and disease PBPK models underwent a four-way validation. The verified PBPK models successfully predicted the altered PKs in patients for substrates and inhibitors and recovered the observed statin-rifampicin DDIs in patients and the statin-roxadustat DDIs in HVs within 1.25- and 2-fold error. Further sensitivity analysis revealed that the severe CKD effect on statins PK is mainly mediated by hepatic BCRP for rosuvastatin and OATP1B1/3 for atorvastatin. The magnitude of statin-roxadustat DDI in patients with severe CKD was predicted to be similar to that in HVs. PBPK-guided suitable dose regimens were identified to minimize the risk of side effects or therapeutic failure of statins when co-administered with roxadustat.
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| 26. |
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| 27. |
- Duarte, Ana I., et al.
(author)
-
Dual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington's Disease
- 2018
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
-
Journal article (peer-reviewed)abstract
- Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition. In this study, we targeted energy metabolism in R6/2 mice using a co-administration of liraglutide and ghrelin. We investigated their effect on brain cortical hormone-mediated intracellular signalling pathways, metabolic and apoptotic markers, and the impact on motor function in HD. We here demonstrate that liraglutide, alone or together with ghrelin (subcutaneous daily injections of 150 μg/kg (ghrelin) and 0.2 mg/kg (liraglutide), for 2 weeks), normalized glucose homeostatic features in the R6/2 mouse, without substantially affecting body weight or body composition. Liraglutide alone decreased brain cortical active GLP-1 and IGF-1 levels in R6/2 mice, alongside higher ADP levels. Liraglutide plus ghrelin decreased brain insulin, lactate, AMP and cholesterol levels in R6/2 mice. Taken together, our findings encourage further studies targeting energy metabolism in HD.
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| 28. |
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| 29. |
- Edvardsson, David, et al.
(author)
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Everyday activities for people with dementia in residential aged care : associations with person-centredness and quality of life.
- 2014
-
In: International journal of older people nursing. - : Blackwell Publishing. - 1748-3743 .- 1748-3735. ; 9, s. 269-276
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Providing everyday activities is central to high quality residential aged care, but further research is needed on the association between activity participation, person-centred care and quality of life. AIMS AND OBJECTIVES: To explore the point-prevalence of participation in everyday activities for residents with dementia within a national sample of Swedish residential aged care units and to explore if residents participating in everyday activities lived in more person-centred units and/or had higher quality of life as compared to residents not participating in everyday activities. DESIGN AND METHODS: A cross-sectional design was used to collect valid and reliable questionnaire data on activity participation, unit person-centredness and quality of life in a sample of residents in residential aged care (n = 1266). RESULTS: Only 18% of residents participated in everyday activities such as making coffee, setting or clearing the table, cleaning or watering plants, 62% participated in outdoor walks, 27% participated in parlour games, and 14% and 13% participated in excursions and church visits, respectively. Those residents who had participated in everyday activities lived in more person-centred units, had significantly higher quality of life and higher cognitive scores as compared to those residents who had not participated in everyday activities. CONCLUSIONS: Even though the prevalence of resident participation in everyday activities was low, resident participation was significantly associated with unit person-centredness and resident quality of life. It seems that everyday activities that are routine and commonplace to residential aged care can be potent nursing interventions for promoting resident quality of life. IMPLICATIONS FOR PRACTICE: The study indicates that residents can benefit from participation in everyday activities that are commonly occurring in aged care practice. It seems that such everyday tasks and procedures can provide fruitful ways to make person-centred care happen in clinical practice, and ways to increasingly involve residents with cognitive impairment need to be further developed.
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| 30. |
- Edvardsson, David, et al.
(author)
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Person-centred climate questionnaire (PCQ-S) : establishing reliability and cut-off scores in residential aged care
- 2015
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In: Journal of Nursing Management. - : John Wiley & Sons. - 0966-0429 .- 1365-2834. ; 23:3, s. 315-323
-
Journal article (peer-reviewed)abstract
- AimThis study aimed to establish reliability and cut-off scores for the person-centred climate questionnaire - staff version (PCQ-S) in residential aged care. BackgroundA number of tools have emerged recently to measure person-centredness, and these need psychometric evaluation and cut-off scores to enhance utilisation and interpretation. MethodA cross-sectional survey design was employed in a Swedish sample of residential aged care staff (n=1237). Psychometric evaluation using Cronbach's alpha and item-total correlation was used, together with establishing cut-off scores based on quartile scores. ResultThe PCQ-S had satisfactory psychometric properties and the following total scale cut-off scores for unit person-centredness were suggested: 49 (well below average'), 50-56 (below average'), 57-62 (above average') and 63 (well above average'). These cut-off scores were clinically meaningful as they separated the sample into four groups in which staff in more person-centred units reported significantly higher work satisfaction, social support and less stress of conscience. ConclusionThe PCQ-S has reliability in residential aged care samples, and cut-off scores are provided that provide important fundaments for comparative studies and aggregation of data to explore person-centredness care further. Implications for nursing managementThe study enables managers with ways to measure, interpret and compare levels of person-centredness between units and facilities for research, practice development and/or benchmarking purposes.
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| 31. |
- Edvardsson, David, et al.
(author)
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The Umeå Ageing and health research programme (U-age) : exploring person-centred care and health promoting living conditions for an ageing population
- 2016
-
In: Nordic journal of nursing research. - : Sage Publications. - 2057-1585 .- 2057-1593. ; 36:3, s. 168-174
-
Journal article (peer-reviewed)abstract
- The aim of this article is to describe the Umeå ageing and health research programme that explores person-centred care and health-promoting living conditions for an ageing population in Sweden, and to place this research programme in a national and international context of available research evidence and trends in aged care policy and practice. Contemporary trends in aged care policy includes facilitating ageing in place and providing person-centred care across home and aged care settings, despite limited evidence on how person-centred care can be operationalised in home care services and sheltered housing accommodation for older people. The Umeå ageing and health research programme consists of four research projects employing controlled, cross-sectional and longitudinal designs across ageing in place, sheltered housing, and nursing homes. The research programme is expected to provide translational knowledge on the structure, content and outcomes of person-centred care and health-promoting living conditions in home care, sheltered housing models, and nursing homes for older people and people with dementia.
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| 32. |
- Fischer, Anders, 1951, et al.
(author)
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Vittrup Man-The life-history of a genetic foreigner in Neolithic Denmark.
- 2024
-
In: PloS one. - 1932-6203. ; 19:2
-
Journal article (peer-reviewed)abstract
- The lethally maltreated body of Vittrup Man was deposited in a Danish bog, probably as part of a ritualised sacrifice. It happened between c. 3300 and 3100 cal years BC, i.e., during the period of the local farming-based Funnel Beaker Culture. In terms of skull morphological features, he differs from the majority of the contemporaneous farmers found in Denmark, and associates with hunter-gatherers, who inhabited Scandinavia during the previous millennia. His skeletal remains were selected for transdisciplinary analysis to reveal his life-history in terms of a population historical perspective. We report the combined results of an integrated set of genetic, isotopic, physical anthropological and archaeological analytical approaches. Strontium signature suggests a foreign birthplace that could be in Norway or Sweden. In addition, enamel oxygen isotope values indicate that as a child he lived in a colder climate, i.e., to the north of the regions inhabited by farmers. Genomic data in fact demonstrates that he is closely related to Mesolithic humans known from Norway and Sweden. Moreover, dietary stable isotope analyses on enamel and bone collagen demonstrate a fisher-hunter way of life in his childhood and a diet typical of farmers later on. Such a variable life-history is also reflected by proteomic analysis of hardened organic deposits on his teeth, indicating the consumption of forager food (seal, whale and marine fish) as well as farmer food (sheep/goat). From a dietary isotopic transect of one of his teeth it is shown that his transfer between societies of foragers and farmers took place near to the end of his teenage years.
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| 33. |
- Fogelstrand, Linda, 1974, et al.
(author)
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Prognostic Implications of Mutations in NOTCH1 and FBXW7 in Childhood T-ALL Treated According to the NOPHO ALL-1992 and ALL-2000 Protocols
- 2014
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In: Pediatric Blood & Cancer. - : Wiley-Blackwell. - 1545-5009 .- 1545-5017. ; 61:3, s. 424-430
-
Journal article (peer-reviewed)abstract
- Background In children, T-cell acute lymphoblastic leukemia (T-ALL) has inferior prognosis compared with B-cell precursor ALL. In order to improve survival, individualized treatment strategies and thus risk stratification algorithms are warranted, ideally already at the time of diagnosis.Procedure We analyzed the frequency and prognostic implication of mutations in NOTCH1 and FBXW7 in 79 cases of Swedish childhood T-ALL treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL-1992 and ALL-2000 protocols. In a subgroup of patients, we also investigated the functional relevance of NOTCH1 mutations measured as expression of the HES1, MYB, and MYC genes.Results Forty-seven of the cases (59%) displayed mutations in NOTCH1 and/or FBXW7. There was no difference in overall (P=0.14) or event-free survival (EFS) (P=0.10) in patients with T-ALL with mutation(s) in NOTCH1/FBXW7 compared with patients with T-ALL without mutations in any of these genes. T-ALL carrying NOTCH1 mutations had increased HES1 and MYB mRNA expression (HES1 9.21.9 (mean +/- SEM), MYB 8.7 +/- 0.8 (mean +/- SEM)) compared to T-ALL with wild-type NOTCH1 (HES1 1.8 +/- 0.7, MYB 5.1 +/- 1.2, P=0.02 and 0.008, respectively). In cases of T-ALL with high HES1 expression, improved overall (P=0.02) and EFS (P=0.028) was seen.Conclusions Increased NOTCH activity, reflected by increased HES1 expression, is associated with improved outcome in pediatric T-ALL, but its role as a diagnostic tool or a therapeutic target in future clinical treatment protocols remains to be elucidated. Pediatr Blood Cancer 2014;61:424-430. (c) 2013 Wiley Periodicals, Inc.
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| 34. |
- Frei, Karin M, et al.
(author)
-
Mapping human mobility during the third and second millennia BC in present-day Denmark
- 2019
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:8
-
Journal article (peer-reviewed)abstract
- We present results of the largest multidisciplinary human mobility investigation to date of skeletal remains from present-day Denmark encompassing the 3rd and 2nd millennia BC. Through a multi-analytical approach based on 88 individuals from 37 different archaeological localities in which we combine strontium isotope and radiocarbon analyses together with anthropological investigations, we explore whether there are significant changes in human mobility patterns during this period. Overall, our data suggest that mobility of people seems to have been continuous throughout the 3rd and 2nd millennia BC. However, our data also indicate a clear shift in mobility patterns from around 1600 BC onwards, with a larger variation in the geographical origin of the migrants, and potentially including more distant regions. This shift occurred during a transition period at the beginning of the Nordic Bronze Age at a time when society flourished, expanded and experienced an unprecedented economic growth, suggesting that these aspects were closely related.
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| 35. |
- Grahnemo, Louise, et al.
(author)
-
Increased bone mass in a mouse model with low fat mass.
- 2018
-
In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 315:6
-
Journal article (peer-reviewed)abstract
- Mice with impaired acute inflammatory responses within adipose tissue display reduced diet-induced fat mass gain associated with glucose intolerance and systemic inflammation. Therefore, acute adipose tissue inflammation is needed for a healthy expansion of adipose tissue. Because inflammatory disorders are associated with bone loss, we hypothesized that impaired acute adipose tissue inflammation leading to increased systemic inflammation results in a lower bone mass. To test this hypothesis, we used mice overexpressing an adenoviral protein complex - the receptor internalization and degradation (RID) complex that inhibits pro-inflammatory signaling - under the control of the aP2-promotor (RID tg mice), resulting in suppressed inflammatory signaling in adipocytes. As expected, RID tg mice had a lower high-fat diet-induced weight and fat mass gain and higher systemic inflammation than their littermate wild type controls. Contrary to our hypothesis, the RID tg mice had increased bone mass in long bones and vertebrae, affecting trabecular and cortical parameters, as well as improved humeral biomechanical properties. We did not find any differences in bone formation or resorption parameters as determined by histology or enzyme immunoassay. However, bone marrow adiposity, often negatively associated with bone mass, was decreased in male RID tg mice as determined by histological analysis of tibia. In conclusion, mice with reduced fat mass, due to impaired adipose tissue inflammation, have increased bone mass.
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| 36. |
- Gustafsson, Karin L., 1987, et al.
(author)
-
ER alpha expression in T lymphocytes is dispensable for estrogenic effects in bone
- 2018
-
In: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 238:2, s. 129-136
-
Journal article (peer-reviewed)abstract
- Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERa) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERa expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERa expression specifically in T lymphocytes (Lck-ERa-/-) and ERaflox/flox littermate (control) mice. Deletion of ERa expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERa-/compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERa-/- mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERa-/- led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERa in T lymphocytes. In conclusion, ERa expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.
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| 37. |
- Hansson, Martin, et al.
(author)
-
Tunga ting med text : Sivert Grubbe och eftermälet
- 2019
-
In: Tidens landskap : En vänbok till Anders Andrén - En vänbok till Anders Andrén. - 0349-4128. - 9789188909121 ; :77, s. 48-50
-
Book chapter (peer-reviewed)abstract
- Den här artikeln diskuterar den danske adelsmannen Sivert Grubbe och de tavlor med långa inskrifter på latin som han satte upp på sina herrgårdar Torup och Hovdala på 1630-talet. Tavlorna sattes upp mot slutet av hans liv och kan ses som ett försök att skapa ett minnesmärke över sig själv, att styra det egna eftermälet.
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| 38. |
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| 39. |
- Hjalte, Johanna, et al.
(author)
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Aggregation Behavior of Structurally Similar Therapeutic Peptides Investigated by 1H NMR and All-Atom Molecular Dynamics Simulations
- 2022
-
In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 19:3, s. 904-917
-
Journal article (peer-reviewed)abstract
- Understanding of peptide aggregation propensity is an important aspect in pharmaceutical development of peptide drugs. In this work, methodologies based on all-atom molecular dynamics (AA-MD) simulations and 1H NMR (in neat H2O) were evaluated as tools for identification and investigation of peptide aggregation. A series of structurally similar, pharmaceutically relevant peptides with known differences in aggregation behavior (D-Phe6-GnRH, ozarelix, cetrorelix, and degarelix) were investigated. The 1H NMR methodology was used to systematically investigate variations in aggregation with peptide concentration and time. Results show that 1H NMR can be used to detect the presence of coexisting classes of aggregates and the inclusion or exclusion of counterions in peptide aggregates. Interestingly, results suggest that the acetate counterions are included in aggregates of ozarelix and cetrorelix but not in aggregates of degarelix. The peptides investigated in AA-MD simulations (D-Phe6-GnRH, ozarelix, and cetrorelix) showed the same rank order of aggregation propensity as in the NMR experiments. The AA-MD simulations also provided molecular-level insights into aggregation dynamics, aggregation pathways, and the influence of different structural elements on peptide aggregation propensity and intermolecular interactions within the aggregates. Taken together, the findings from this study illustrate that 1H NMR and AA-MD simulations can be useful, complementary tools in early evaluation of aggregation propensity and formulation development for peptide drugs.
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| 40. |
- Hjalte, Johanna, et al.
(author)
-
Modulating protein unfolding and refolding via the synergistic association of an anionic and a nonionic surfactant
- 2024
-
In: Journal of Colloid and Interface Science. - 0021-9797. ; 672, s. 244-255
-
Journal article (peer-reviewed)abstract
- Hypothesis: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation. Experiments: In this work, the behavior of three model proteins (human growth hormone, bovine serum albumin, and β-lactoglobulin) was investigated in the presence of the anionic surfactant sodium dodecylsulfate, the nonionic surfactant β-dodecylmaltoside, and mixtures of both surfactants. The transitions occurring to the proteins were determined using intrinsic fluorescence spectroscopy and far-UV circular dichroism. Based on these results, we developed a detailed interaction model for human growth hormone. Using nuclear magnetic resonance and contrast-variation small-angle neutron scattering, we studied the amino acid environment and the conformational state of the protein. Findings: The results demonstrate the key role of surfactant cooperation in defining the conformational state of the proteins, which can shift away or toward the folded state depending on the nonionic-to-ionic surfactant ratio. Dodecylmaltoside, initially a non-interacting surfactant, can unexpectedly associate with sodium dodecylsulfate-unfolded proteins to further impact their conformation at low nonionic-to-ionic surfactant ratio. When this ratio increases, the protein begins to retrieve the folded state. However, the native conformation cannot be fully recovered due to remnant surfactant molecules still adsorbed to the protein. This study demonstrates that the conformational landscape of the protein depends on a delicate interplay between the surfactants, ultimately controlled by the ratio between them, resulting in unpredictable changes in the protein conformation.
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| 41. |
- Hoque, Sanzana, et al.
(author)
-
Skeletal muscle regeneration is altered in the R6/2 mouse model of Huntington’s disease
- 2022
-
Other publication (other academic/artistic)abstract
- Huntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise.In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice.We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage.Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models.
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| 42. |
- Horkeby, Karin L, et al.
(author)
-
Phosphorylation of S122 in ERα is important for the skeletal response to estrogen treatment in male mice
- 2022
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
-
Journal article (peer-reviewed)abstract
- Estrogen receptor alpha (ERα) signaling has beneficial skeletal effects in males. ERα signaling also affects other tissues, and to find bone-specific treatments, more knowledge regarding tissue-specific ERα signaling is needed. ERα is subjected to posttranslational modifications, including phosphorylation, which can influence ERα function in a tissue-specific manner. To determine the importance of phosphorylation site S122 (corresponding to human ERα site S118) for the skeleton and other tissues, male mice with a S122A mutation were used. Total areal bone mineral density was similar between gonadal intact S122A and WT littermates followed up to 12months of age, and weights of estrogen-responsive organs normalized for body weight were unchanged between S122A and WT males at both 3 and 12months of age. Interestingly, 12-month-old S122A males had decreased body weight compared to WT. To investigate if site S122 affects the estrogen response in bone and other tissues, 12-week-old S122A and WT males were orchidectomized (orx) and treated with estradiol (E2) or placebo pellets for four weeks. E2 increased cortical thickness in tibia in both orx WT (+ 60%, p < 0.001) and S122A (+ 45%, p < 0.001) males. However, the E2 effect on cortical thickness was significantly decreased in orx S122A compared to WT mice (−24%, p < 0.05). In contrast, E2 affected trabecular bone and organ weights similarly in orx S122A and WT males. Thus, ERα phosphorylation site S122 is required for a normal E2 response specifically in cortical bone in male mice, a finding that may have implications for development of future treatments against male osteoporosis.
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| 43. |
- Khan, Omar M., 1980, et al.
(author)
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Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice.
- 2011
-
In: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39
-
Journal article (peer-reviewed)abstract
- RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
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| 44. |
- Lagerquist, Marie K, et al.
(author)
-
Acute fat loss does not affect bone mass
- 2021
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Obesity has previously been thought to protect bone since high body weight and body mass index are associated with high bone mass. However, some more recent studies suggest that increased adiposity negatively impacts bone mass. Here, we aimed to test whether acute loss of adipose tissue, via adipocyte apoptosis, alters bone mass in age-related obese mice. Adipocyte apoptosis was induced in obese male FAT-ATTAC mice through AP20187 dimerizer-mediated activation of caspase 8 selectively in adipocytes. In a short-term experiment, dimerizer was administered to 5.5 month-old mice that were terminated 2 weeks later. At termination, the total fat mass weighed 58% less in dimerizer-treated mice compared with vehicle-treated controls, but bone mass did not differ. To allow for the detection of long-term effects, we used 9-month-old mice that were terminated six weeks after dimerizer administration. In this experiment, the total fat mass weighed less (- 68%) in the dimerizer-treated mice than in the controls, yet neither bone mass nor biomechanical properties differed between groups. Our findings show that adipose tissue loss, despite the reduced mechanical loading, does not affect bone in age-related obese mice. Future studies are needed to test whether adipose tissue loss is beneficial during more severe obesity.
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| 45. |
- Lilliengren, Peter, et al.
(author)
-
Patient attachment to therapist rating scale : development and psychometric properties
- 2014
-
In: Psychotherapy Research. - : Informa UK Limited. - 1050-3307 .- 1468-4381. ; 24:2, s. 184-201
-
Journal article (peer-reviewed)abstract
- Objective: To report on the development and initial psychometric properties of a new rating scale for patent-therapist attachment. Method: Seventy interviews from the Young Adult Psychotherapy Project (YAPP) were rated. Results: Excellent internal consistency (Cronbach's > .90) was observed for all four subscales (Security, Deactivation, Hyperactivation, and Disorganization). Three subscales showed good inter-rater reliability (ICC > .60), while one (Hyperactivation) had poor (ICC < .40). Correlations with measures of alliance, mental representations, and symptom distress support the construct validity of the reliable subscales. Exploratory factor analysis indicated three underlying factors explaining 82% of the variance. Conclusions: The Patient Attachment to Therapist Rating Scale is a promising approach for assessing the quality of attachment to therapist from patient narratives. Future development should focus on improving the discrimination of the insecure subscales.
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| 46. |
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| 47. |
- Lood, Qarin, 1981, et al.
(author)
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Effects of a staff education programme about person-centred care and promotion of thriving on relatives' satisfaction with quality of care in nursing homes: a multi-centre, non-equivalent controlled before-after trial
- 2020
-
In: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 20:1
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Journal article (peer-reviewed)abstract
- Background As part of a nursing home intervention study, the aim of this paper was 1) to evaluate the effects of a staff education programme about person-centred care and promotion of thriving on relatives' satisfaction with quality of care and their perceptions of the person-centredness of the environment, and 2) to outline factors of importance to explain the variance in relatives' satisfaction with quality of care. Relatives are often referred to as vital for the operationalisation of person-centredness in nursing homes, representing an important source of information for care planning and quality of care assessments. However, the evidence for effects of person-centredness in nursing homes on relatives' experiences is sparse and little is known on what could explain their satisfaction with the quality of care. Methods A multi-centre, non-equivalent controlled group before-after design with study sites in Australia, Norway and Sweden. Staff in the intervention group participated in a 14-month education on person-centredness, person-centred care, thriving and caring environment. Staff in the control group received a one-hour lecture before the intervention period. Data were collected at baseline, after the intervention and six months after the end of the intervention, and analysed using descriptive statistics, a generalised linear model and hierarchical multiple regression. Results In general, relatives from both the intervention and control nursing homes were satisfied with the quality of care, and no statistically significant overall between-group-effects of the intervention were revealed on satisfaction with quality of care or perceptions of the person-centredness of environment. A person-centred environment in terms of safety and hospitality were identified as factors of prominent importance for the relatives' satisfaction with the quality of care. Conclusion The findings of this paper provide a foundation for future research in terms of intervention design in nursing home contexts. Staff availability, approachability, competence and communication with relatives may be important factors to consider to improve quality of care from the perspective of relatives, but more research both with and for relatives to people living in nursing homes is necessary to identify the keys to success.
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- Mohammad Al-Amily, Israa, et al.
(author)
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Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane
- 2023
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In: Biomolecules. - : MDPI AG. - 2218-273X. ; 13:3
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Journal article (peer-reviewed)abstract
- The activation of G Protein-Coupled Receptor 56 (GPR56), also referred to as Adhesion G-Protein-Coupled Ceceptor G1 (ADGRG1), by Collagen Type III (Coll III) prompts cell growth, proliferation, and survival, among other attributes. We investigated the signaling cascades mediating this functional effect in relation to the mitochondrial outer membrane voltage-dependent anion Channel-1 (VDAC1) expression in pancreatic β-cells. GPR56KD attenuated the Coll III-induced suppression of P70S6K, JNK, AKT, NFκB, STAT3, and STAT5 phosphorylation/activity in INS-1 cells cultured at 20 mM glucose (glucotoxicity) for 72 h. GPR56-KD also increased Chrebp, Txnip, and Vdac1 while decreasing Vdac2 mRNA expression. In GPR56-KD islet β-cells, Vdac1 was co-localized with SNAP-25, demonstrating its plasma membrane translocation. This resulted in ATP loss, reduced cAMP production and impaired glucose-stimulated insulin secretion (GSIS) in INS-1 and human EndoC βH1 cells. The latter defects were reversed by an acute inhibition of VDAC1 with an antibody or the VDAC1 inhibitor VBIT-4. We demonstrate that Coll III potentiates GSIS by increasing cAMP and preserving β-cell functionality under glucotoxic conditions in a GPR56-dependent manner by attenuating the inflammatory response. These results emphasize GPR56 and VDAC1 as drug targets in conditions with impaired β-cell function.
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- Movérare-Skrtic, Sofia, et al.
(author)
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The bone-sparing effects of estrogen and WNT16 are independent of each other
- 2015
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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. ; 112:48, s. 14972-14977
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Journal article (peer-reviewed)abstract
- Wingless-type MMTV integration site family (WNT)16 is a key regulator of bone mass with high expression in cortical bone, and Wnt16-/- mice have reduced cortical bone mass. As Wnt16 expression is enhanced by estradiol treatment, we hypothesized that the bone-sparing effect of estrogen in females isWNT16-dependent. This hypothesis was tested in mechanistic studies using two genetically modified mouse models with either constantly high osteoblastic Wnt16 expression or no Wnt16 expression. We developed a mouse model with osteoblast-specific Wnt16 overexpression (Obl-Wnt16). These mice had several-fold elevated Wnt16 expression in both trabecular and cortical bone compared with wild type (WT) mice. Obl- Wnt16 mice displayed increased total body bone mineral density (BMD), surprisingly caused mainly by a substantial increase in trabecular bone mass, resulting in improved bone strength of vertebrae L3. Ovariectomy (ovx) reduced the total body BMD and the trabecular bone mass to the same degree in Obl-Wnt16 mice and WT mice, suggesting that the bone-sparing effect of estrogen is WNT16-independent. However, these bone parameters were similar in ovx Obl- Wnt16 mice and sham operated WT mice. The role of WNT16 for the bone-sparing effect of estrogen was also evaluated in Wnt16-/- mice. Treatment with estradiol increased the trabecular and cortical bone mass to a similar extent in both Wnt16-/- and WT mice. In conclusion, the bone-sparing effects of estrogen and WNT16 are independent of each other. Furthermore, loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. WNT16- targeted therapies might be useful for treatment of postmenopausal trabecular bone loss.
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