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- Johansson, Sverker, et al.
(författare)
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The Swedish occupational fatigue inventory in people with multiple sclerosis
- 2008
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Ingår i: Journal of Rehabilitation Medicine. - Oslo : Taylor & Francis. - 1650-1977 .- 1651-2081. ; 40:9, s. 737-743
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the applicability of the Swedish Occupational Fatigue Inventory and its ability to identify different dimensions of fatigue in people with multiple sclerosis with varying, degrees of disease severity, and the correlation of each of its 5 dimensions with the Fatigue Severity Scale.Design: An observational. prospective study.Subjects: Two hundred and nineteen outpatients: 59.5% had mild. 170%, moderate and 23.5% severe disease severity; 83%, received immunomodulatory treatment.Methods: Both questionnaires were administered at inclusion, and at 12 and 24 months. Analyses of internal consistency. item-total correlation, factor analysis and tests of correlations were performed.Results: The instrument was completed by 97% of subjects. Internal consistency was satisfactory in the dimensions Lack of energy, Lack of motivation and Sleepiness, but not in Physical exertion and Physical discomfort. Factor analysis revealed that all but 3 items (2 in Physical exertion, 1 in Physical discomfort) loaded satisfactorily in 5 dimensions. Correlations between the dimensions and the Fatigue Severity Scale were low, except for a moderate correlation found for Lack of energy.Conclusion: The dimensions Lack of energy, Lack of motivation and Sleepiness appear applicable for use in people with multiple sclerosis. Further development of the physical dimensions and studies on the instrument's capacity to measure changes are needed.
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| 2. |
- Sainz-Jaspeado, Miguel, et al.
(författare)
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Palmdelphin Regulates Nuclear Resilience to Mechanical Stress in the Endothelium
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:20, s. 1629-1645
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Tidskriftsartikel (refereegranskat)abstract
- Background: PALMD (palmdelphin) belongs to the family of paralemmin proteins implicated in cytoskeletal regulation. Single nucleotide polymorphisms in the PALMD locus that result in reduced expression are strong risk factors for development of calcific aortic valve stenosis and predict severity of the disease.Methods: Immunodetection and public database screening showed dominant expression of PALMD in endothelial cells (ECs) in brain and cardiovascular tissues including aortic valves. Mass spectrometry, coimmunoprecipitation, and immunofluorescent staining allowed identification of PALMD partners. The consequence of loss of PALMD expression was assessed in small interferring RNA-treated EC cultures, knockout mice, and human valve samples. RNA sequencing of ECs and transcript arrays on valve samples from an aortic valve study cohort including patients with the single nucleotide polymorphism rs7543130 informed about gene regulatory changes.Results: ECs express the cytosolic PALMD-KKVI splice variant, which associated with RANGAP1 (RAN GTP hydrolyase activating protein 1). RANGAP1 regulates the activity of the GTPase RAN and thereby nucleocytoplasmic shuttling via XPO1 (Exportin1). Reduced PALMD expression resulted in subcellular relocalization of RANGAP1 and XPO1, and nuclear arrest of the XPO1 cargoes p53 and p21. This indicates an important role for PALMD in nucleocytoplasmic transport and consequently in gene regulation because of the effect on localization of transcriptional regulators. Changes in EC responsiveness on loss of PALMD expression included failure to form a perinuclear actin cap when exposed to flow, indicating lack of protection against mechanical stress. Loss of the actin cap correlated with misalignment of the nuclear long axis relative to the cell body, observed in PALMD-deficient ECs, Palmd(-/-) mouse aorta, and human aortic valve samples derived from patients with calcific aortic valve stenosis. In agreement with these changes in EC behavior, gene ontology analysis showed enrichment of nuclear- and cytoskeleton-related terms in PALMD-silenced ECs.Conclusions: We identify RANGAP1 as a PALMD partner in ECs. Disrupting the PALMD/RANGAP1 complex alters the subcellular localization of RANGAP1 and XPO1, and leads to nuclear arrest of the XPO1 cargoes p53 and p21, accompanied by gene regulatory changes and loss of actin-dependent nuclear resilience. Combined, these consequences of reduced PALMD expression provide a mechanistic underpinning for PALMD's contribution to calcific aortic valve stenosis pathology.
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| 4. |
- Uchtenhagen, Hannes, et al.
(författare)
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Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein.
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 192:12, s. 5802-5812
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.
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